+publisher:"Penn State University" +contributor:("Yanming Wang, Committee Member")

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1. Xiang, Jie. REGULATION OF STRESS ERYTHROPOIESIS: INTERACTION BETWEEN MICROENVIRONMENT AND STRESS ERYTHROID PROGENITORS.

Degree: 2014, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/23422

► Steady-state erythropoiesis occurs in the bone marrow and produces erythrocytes at a constant rate. Its role is to replace “worn out” red blood cells that… (more)

▼ Steady-state erythropoiesis occurs in the bone marrow and produces erythrocytes at a constant rate. Its role is to replace “worn out” red blood cells that are removed by the spleen. While in response to acute anemia and tissue hypoxia, another type of erythropoiesis, stress erythropoiesis, is induced to rapidly generate new erythrocytes to compensate the loss. Previously our lab showed that stress erythropoiesis utilizes various signals and stress erythroid progenitors that are distinct from steady state erythropoiesis. Initially, bone marrow CD34+KSL cells migrate into the spleen and interact with hedgehog ligands, which induce the expression of BMP4. Hedgehog and BMP4 together specify the stress erythroid fate. Further work showed that there are three distinct populations of stress erythroid progenitors that expand in the spleen during the recovery from bone marrow transplantation. They were identified as Population I (Kit+CD71-/medTer119lo/-), Population II (Kit+CD71highTer119med) and Population III (Kit+CD71-/medTer119high). The appearance of three populations suggested the temporal order for their development: Population I gives rise to Population II and Population II gives rise to Population III. Although the number of Population I cells increased in the pre-recovery stage, we didn’t observe stress BFU-E until day 8, which indicated that these cells proliferated but couldn’t differentiate in the early time. Then they acquired the ability to differentiate into stress BFU-E. Finally, BMP4, SCF and hypoxia are required for the expansion and differentiation of stress BFU-E during the late stage of the recovery from acute anemia. My work mainly focuses on the following questions: 1. What is the role of GDF15 in the regulation of stress erythropoiesis? 2. How to identify the self-renewing Population I cells and differentiating Population I cells? 3. How does Epo regulate the transition from expansion to differentiation of stress erythroid progenitors? These questions will be answered in Chapters 2, 3 and 4. In Chapter 2, my work showed that GDF15-/- mice are deficient in recovery from acute anemia and fail to provide short-term radioprotection. GDF15 plays a critical role in stress erythropoiesis by inducing and maintain hypoxia dependent BMP4 expression. My work in chapter 3 further described the development of distinct stress erythroid progenitors with increasing maturity based on their expression of cell surface markers CD34, CD133, Kit and Sca1. Here we developed an in vitro culture system and identified CD34+CD133+KS population as the early stress erythroid progenitors that have self-renewal ability and CD34-CD133-KS population as the later stress erythroid progenitors that have differentiation ability. The bone marrow transplantation data also showed CD34+CD133+KS cells expanded on day6 and CD34-CD133-KS cells were increased on day 12 post-transplantation. Then I further demonstrated that similar to murine bone marrow, human bone marrow contains cells can exhibit stress erythropoiesis ability and generate… Advisors/Committee Members: Robert Paulson, Dissertation Advisor/Co-Advisor, Robert Paulson, Committee Chair/Co-Chair, Ross Cameron Hardison, Committee Member, Zhi Chun Lai, Committee Member, Kumble Sandeep Prabhu, Committee Member, Yanming Wang, Committee Member, Naomi S Altman, Committee Member.

Subjects/Keywords: Stress erythropoiesis; Stem cell; Epo; progenitors; Anemia

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APA (6^th Edition):

Xiang, J. (2014). REGULATION OF STRESS ERYTHROPOIESIS: INTERACTION BETWEEN MICROENVIRONMENT AND STRESS ERYTHROID PROGENITORS. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/23422

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Xiang, Jie. “REGULATION OF STRESS ERYTHROPOIESIS: INTERACTION BETWEEN MICROENVIRONMENT AND STRESS ERYTHROID PROGENITORS.” 2014. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/23422.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Xiang, Jie. “REGULATION OF STRESS ERYTHROPOIESIS: INTERACTION BETWEEN MICROENVIRONMENT AND STRESS ERYTHROID PROGENITORS.” 2014. Web. 19 Jan 2021.

Vancouver:

Xiang J. REGULATION OF STRESS ERYTHROPOIESIS: INTERACTION BETWEEN MICROENVIRONMENT AND STRESS ERYTHROID PROGENITORS. [Internet] [Thesis]. Penn State University; 2014. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/23422.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Xiang J. REGULATION OF STRESS ERYTHROPOIESIS: INTERACTION BETWEEN MICROENVIRONMENT AND STRESS ERYTHROID PROGENITORS. [Thesis]. Penn State University; 2014. Available from: https://submit-etda.libraries.psu.edu/catalog/23422

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

2. Yang, Jie. programming of CCR10+ skin-homing innate lymphocytes in fetal thymus and adult skin-draining lymph nodes for establishment of skin immune system.

Degree: 2015, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/26429

► The skin is directly exposed to the environment and immune cells in the skin provide the first line of protection against invading pathogens. Innate and… (more)

▼ The skin is directly exposed to the environment and immune cells in the skin provide the first line of protection against invading pathogens. Innate and innate-like lymphocytes respond quickly during infection and coordinate with adaptive immune system to clear pathogens. Innate lymphoid cells (ILCs) are innate lymphocytes that lack rearranged antigen-specific receptors and preferentially localized in barrier tissues, such as skin. They play critical roles in homeostatic regulation but also contribute to inflammatory diseases when dysregulated. Mechanisms regulating the development and function of ILCs in the skin are poorly understood. I report that during the perinatal stage, the skin-specific homing property and effector potential of thymic natural killer (NK) cells, a subset of ILCs, are programmed in the thymus for their rapid localization into the skin and functions. This may represent an evolutionally important mechanism that directs innate lymphocytes to the skin of newborns, whose adaptive immune system has not fully developed, for early protection. Moreover, NK cells, including thymic NK cells, generated in the perinatal stage contribute to the skin immune system in adults. In addition, skin-homing ILCs can be generated in skin-draining lymph nodes (sLNs) of adults. Under homeostatic condition, ILCs are continuously activated in sLNs to acquire the expression of CCR10 for their localization into the skin. Foxn1 and Notch/ligands signals are involved in the induction of CCR10 expression on ILCs in fetal/neonatal thymi and adult sLNs for their skin localization. The generation of CCR10+ ILCs and their maintenance in the skin are dependent on T cell-regulated homeostatic environments and are suppressed under inflammatory conditions. Reciprocally, ILCs regulate the homeostasis of skin-resident T cells. My findings provide insights of mechanisms that regulate the establishment of innate lymphocytes in the skin and their cross-regulation with adaptive immune cells. Advisors/Committee Members: Na Xiong, Dissertation Advisor/Co-Advisor, Margherita Teresa Anna Cantorna, Committee Member, Pamela Hankey Giblin, Committee Member, Girish Soorappa Kirimanjeswara, Committee Member, Yanming Wang, Committee Member.

Subjects/Keywords: innate lymphoid cells; skin-homing; CCR10; fetal thymic programming

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APA (6^th Edition):

Yang, J. (2015). programming of CCR10+ skin-homing innate lymphocytes in fetal thymus and adult skin-draining lymph nodes for establishment of skin immune system. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/26429

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Yang, Jie. “programming of CCR10+ skin-homing innate lymphocytes in fetal thymus and adult skin-draining lymph nodes for establishment of skin immune system.” 2015. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/26429.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Yang, Jie. “programming of CCR10+ skin-homing innate lymphocytes in fetal thymus and adult skin-draining lymph nodes for establishment of skin immune system.” 2015. Web. 19 Jan 2021.

Vancouver:

Yang J. programming of CCR10+ skin-homing innate lymphocytes in fetal thymus and adult skin-draining lymph nodes for establishment of skin immune system. [Internet] [Thesis]. Penn State University; 2015. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/26429.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Yang J. programming of CCR10+ skin-homing innate lymphocytes in fetal thymus and adult skin-draining lymph nodes for establishment of skin immune system. [Thesis]. Penn State University; 2015. Available from: https://submit-etda.libraries.psu.edu/catalog/26429

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

3. Achary, Bhavana Gopalakrishnan. Role of chromatin in promoter proximal pausing in Drosophila.

Degree: 2013, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/19838

► RNA polymerase II pauses in the promoter proximal region of thousands of genes. Amongst the various factors that contribute to pausing, chromatin architecture in the… (more)

▼ RNA polymerase II pauses in the promoter proximal region of thousands of genes. Amongst the various factors that contribute to pausing, chromatin architecture in the promoter proximal region is thought to be one of them. In vitro experiments have shown that nucleosomes can impede elongation of RNA Pol II. Genome wide maps of Pol II and nucleosomes in Drosophila indicate a dynamic interplay between the two. Currently, there are two prevalent models regarding the relationship between paused Pol II and nucleosome positioning. The first model indicates that a positioned nucleosome could contribute to pausing of RNA Pol II. The second model suggests that it is the paused Pol II that contributes to determining nucleosome organization in the promoter proximal region of a gene. In this study, I asked the question, what is the effect on nucleosome position when the position of paused Pol II is changed? To answer this, I determined the position of paused Pol II in embryos from wild type flies and flies with a mutant form of RNA Pol II. Permanganate footprinting experiments showed that the mutant RNA Pol II is paused closer to the transcription start site than in wild type. I mapped the nucleosomes in wild type and mutant to see if the shift in the paused Pol II affected the nucleosome position. The results indicate that the position of +1 nucleosome does not change when the position of paused RNA Pol II is shifted. Pausing is widely recognized as an important step in regulation of gene expression and the mechanism of pausing and the factors involved are under investigation. The Drosophila hsp70 gene has long been regarded as a model gene to study promoter proximal pausing. Transcription of the hsp70 gene involves distinct steps, which include establishment of a paused Pol II, activation and release of the paused Pol II into productive elongation. Various factors are implicated in regulating these distinct steps. I have investigated the effects of depleting some of these factors on transcription of hsp70. Using a beta-galactosidase reporter assay as an initial screen, I chose several factors that when depleted, showed reduced hsp70 transcription. Some of the factors are known to be important in transcription of hsp70, such as the activator HSF and the Pol II CTD kinase, PTEF-b. One surprising result was the effect of depletion of HDAC3. HDAC3 depletion resulted in a decreased level of hsp70 expression, both in the beta-gal assay and mRNA measurements. Upon further investigation, I observed that HDAC3 depletion affected RNA Pol II recruitment and impaired pausing on the hsp70 gene. Advisors/Committee Members: David Scott Gilmour, Dissertation Advisor/Co-Advisor, David Scott Gilmour, Committee Chair/Co-Chair, Song Tan, Committee Member, Joseph C. Reese, Committee Member, Yanming Wang, Committee Member, Pamela Hankey Giblin, Special Member.

Subjects/Keywords: chromatin; pausing; nucleosome positioning; histone deacetylases

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Achary, B. G. (2013). Role of chromatin in promoter proximal pausing in Drosophila. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/19838

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Achary, Bhavana Gopalakrishnan. “Role of chromatin in promoter proximal pausing in Drosophila.” 2013. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/19838.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Achary, Bhavana Gopalakrishnan. “Role of chromatin in promoter proximal pausing in Drosophila.” 2013. Web. 19 Jan 2021.

Vancouver:

Achary BG. Role of chromatin in promoter proximal pausing in Drosophila. [Internet] [Thesis]. Penn State University; 2013. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/19838.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Achary BG. Role of chromatin in promoter proximal pausing in Drosophila. [Thesis]. Penn State University; 2013. Available from: https://submit-etda.libraries.psu.edu/catalog/19838

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

4. Chen, Yueying. IDENTIFICATION AND CHARACTERIZATION OF PATHOGEN EFFECTOR- HOST TARGET INTERACTIONS INVOLVED IN RICE BLAST DISEASE.

Degree: 2016, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/13427coy5057

► During the plant-pathogen interaction, plants have evolved a multi-layered immune system to overcome pathogen infection, whereas pathogens have gained broad capabilities to defeat host defense… (more)

▼ During the plant-pathogen interaction, plants have evolved a multi-layered immune system to overcome pathogen infection, whereas pathogens have gained broad capabilities to defeat host defense by secreting effector proteins into plant cells to interfere with host physiology. Rice blast disease, caused by fungal pathogen Magnaporthe oryzae, is an important plant disease and the model pathosystem for studying the monocot plant-fungus interactions. However, little is known regarding how M. oryzae effectors interact with rice proteins for host defense suppression and fungal infection. This study aims to shed light on molecular and biochemical mechanisms of the rice-M. oryzae interaction by functionally characterizing some M. oryzae effectors and their host target proteins. In this study, Yeast two-Hybrid (Y2H) screenings were performed using four fungal effectors as baits to identify their interacting rice proteins. These pathogen effector-host protein interactions were further confirmed using in vitro GST pull-down assay and in vivo bimolecular fluorescence complementation (BiFC) assay. An M. oryzae effector-rice protein interaction map was then established by integrating the data from this study and previously published information. These putative host targets include several interesting rice proteins such as chromatin remodeler OsHIRA, ubiquitin-like protein OsNPI, and transcription factor OsVOZ1. Functional prediction and categorization of host target proteins reveal that M. oryzae effectors appear to favorably target host Ubiquitin Proteasome System (UPS) and nuclear processes. Two M. oryzae Zinc Finger Effectors (MoZFEs) were individually expressed in transgenic rice lines (MoZFEs-OX) to investigate their function in plant cells. Interestingly, MoZFEs-OX lines exhibited growth and developmental defects and increased susceptibility to M. oryzae infection. Furthermore, transcriptome analysis with RNA-seq reveals a amount of differentially expressed genes (DEGs) in MoZFE1-OX lines vs. wildtype plants. Many of these DEGs are enriched in primary metabolism and defense pathways that correlated with developmental and susceptible phenotypes shown in transgenic rice lines. To elucidate the mode of action of MoZFEs in rice cells, BiFC was used to demonstrate that MoZFEs interact directly with OsHIRA in the nucleus and cytoplasm. HIRA forms gene silencing complex with AS1 and AS2 transcription factors which bind to the promoters of Class I Knotted1-like homeobox (KNOX) genes and regulate plant growth and development in an epigenetic fashion. Bioinformatics analysis of rice gene promoters reveals proximal nucleotide binding motifs that are potentially bound by MoZFE1 and OsHIRA/AS1/AS2. As shown by gene expression analysis with quantitative RT-PCR, the silencing status of KNOX genes maintained by the OsHIRA complex in wild-type leaves was disrupted in MoZFE-OX lines. These bioinformatics predictions and experimental evidence suggest that MoZFEs likely interact with HIRA to interfere with AS1/AS2 binding, and negatively… Advisors/Committee Members: Yinong Yang, Dissertation Advisor/Co-Advisor, Yinong Yang, Committee Chair/Co-Chair, Timothy W Mcnellis, Committee Member, Seogchan Kang, Committee Member, Surinder Chopra, Outside Member, Yanming Wang, Committee Member.

Subjects/Keywords: Rice Blast disease; Effectors; plant immunity; rice; plant development; Disease regulator

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chen, Y. (2016). IDENTIFICATION AND CHARACTERIZATION OF PATHOGEN EFFECTOR- HOST TARGET INTERACTIONS INVOLVED IN RICE BLAST DISEASE. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/13427coy5057

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chen, Yueying. “IDENTIFICATION AND CHARACTERIZATION OF PATHOGEN EFFECTOR- HOST TARGET INTERACTIONS INVOLVED IN RICE BLAST DISEASE.” 2016. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/13427coy5057.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chen, Yueying. “IDENTIFICATION AND CHARACTERIZATION OF PATHOGEN EFFECTOR- HOST TARGET INTERACTIONS INVOLVED IN RICE BLAST DISEASE.” 2016. Web. 19 Jan 2021.

Vancouver:

Chen Y. IDENTIFICATION AND CHARACTERIZATION OF PATHOGEN EFFECTOR- HOST TARGET INTERACTIONS INVOLVED IN RICE BLAST DISEASE. [Internet] [Thesis]. Penn State University; 2016. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/13427coy5057.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chen Y. IDENTIFICATION AND CHARACTERIZATION OF PATHOGEN EFFECTOR- HOST TARGET INTERACTIONS INVOLVED IN RICE BLAST DISEASE. [Thesis]. Penn State University; 2016. Available from: https://submit-etda.libraries.psu.edu/catalog/13427coy5057

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

5. Wu, Weisheng. ROLES OF HISTONE MODIFICATIONS AND TRANSCRIPTION FACTORS IN TRANSCRIPTION REGULATION IN ERYTHROPOIESIS.

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/12534

► Cellular differentiation is a process in which pluripotent cells become morphologically and functionally more specialized cells, which happens in the development from monocellular zygote into… (more)

▼ Cellular differentiation is a process in which pluripotent cells become morphologically and functionally more specialized cells, which happens in the development from monocellular zygote into a multicellular organism system with complex cells and tissues of different types, and also in cell turnover or renewal in adults. This process is largely driven by differential expression of genes so that they are expressed in appropriate temporal and quantitative manners for specific production of proteins that characterize the committed cell type. The output of specific gene expression profiles are substantially controlled by the relevant regulation of gene transcription. Bulk of the studies of gene transcription regulation mechanisms fall in the area of epigenetics which looks into biochemical events that occur without changing the genomic DNA sequence but often result in alterations of gene expression. The main epigenetic events include histone modifications, binding of cis-regulatory elements by transcription factors, chromatin remodeling and DNA methylation. In this thesis, we investigated the distributions of four critical histone modifications, DNase hypersensitivity, and binding sites of three important transcription factors on mouse genome in mouse G1E model which mimics normal erythroid differentiation, allowing us to study the relationship between these epigenetic features and specific gene regulation in erythropoiesis, which is a well-defined cellular differentiation process for maturation of red blood cells. As described in the second chapter of this thesis, we applied ChIP-seq technique to examine the genome-wide distributions of four histone modifications in both erythroid progenitor G1E cells and differentiating erythroblast G1E-ER4+E2 cells. The modifications are H3K4me3 which is associated with promoters, H3K4me1 which marks enhancers, H3K27me3 which associates with gene repression, and H3K9me3 which is associated with heterochromatin. We employed a multivariate HMM to segment the genome into six chromatin states defined by the different distributions of the examined histone modifications. Comparison of the chromatin states between the G1E and its restored cell line G1E-ER4+E2 revealed quite limited alterations of the states in the captured erythroid differentiation process, suggesting a preceding establishment of the chromatin states prior to the GATA1-triggered differentiation, most likely at the stage of erythroid lineage commitment. As a parallel project to the study of histone modifications, we utilized the same ChIP-seq approach and the same G1E system to identify the genome-wide localization of occupancy by three critical transcription factors and investigated their roles in transcription regulation in erythroid differentiation. These factors are GATA1 which is a master regulator of erythropoiesis, TAL1 which is also essential to the lineage and often co-binds DNA with GATA1, and GATA2 which is important for cell pluripotency maintenance in earlier hematopoietic stages. Our observations confirmed the… Advisors/Committee Members: Ross Cameron Hardison, Dissertation Advisor/Co-Advisor, Ross Cameron Hardison, Committee Chair/Co-Chair, Eric Thomas Harvill, Committee Member, Yanming Wang, Committee Member, James Taylor, Committee Member, Francesca Chiaromonte, Committee Member.

Subjects/Keywords: Histone modifications; transcription factors; erythropoiesis; epigenetics; chromatin states

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wu, W. (2011). ROLES OF HISTONE MODIFICATIONS AND TRANSCRIPTION FACTORS IN TRANSCRIPTION REGULATION IN ERYTHROPOIESIS. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/12534

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wu, Weisheng. “ROLES OF HISTONE MODIFICATIONS AND TRANSCRIPTION FACTORS IN TRANSCRIPTION REGULATION IN ERYTHROPOIESIS.” 2011. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/12534.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wu, Weisheng. “ROLES OF HISTONE MODIFICATIONS AND TRANSCRIPTION FACTORS IN TRANSCRIPTION REGULATION IN ERYTHROPOIESIS.” 2011. Web. 19 Jan 2021.

Vancouver:

Wu W. ROLES OF HISTONE MODIFICATIONS AND TRANSCRIPTION FACTORS IN TRANSCRIPTION REGULATION IN ERYTHROPOIESIS. [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/12534.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wu W. ROLES OF HISTONE MODIFICATIONS AND TRANSCRIPTION FACTORS IN TRANSCRIPTION REGULATION IN ERYTHROPOIESIS. [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/12534

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

6. Chen, Yu-Chi. ORGANIC SELENIUM MODIFIES THE OSTEOBLAST INFLAMMATORY STRESS RESPONSE TO BONE METASTATIC BREAST CANCER CELLS IN VITRO AND AFFECTS BREAST CANCER PROGRESSION IN VIVO .

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/12507

► Abstract The skeleton is one of the common metastatic sites for breast cancer. Once breast cancer cells enter the bone microenvironment, they alter the homeostasis… (more)

▼ Abstract The skeleton is one of the common metastatic sites for breast cancer. Once breast cancer cells enter the bone microenvironment, they alter the homeostasis of the bone remodeling system in favor of osteoclasts, which results in osteolysis. Clinically, bisphophonates are used to induce osteoclast apoptosis to prevent further damage but the existing lesions do not heal completely, which suggests that the function of osteoblasts, the bone building cells, is impaired by breast cancer cells. In our laboratory, we discovered that metastatic breast cancer cells (MDA-MB-231) inhibit osteoblast (MC3T3-E1) differentiation and induce apoptosis. Furthermore, breast cancer cells induce an inflammatory response by the osteoblasts, resulting in the production of IL-6, IL-8, MCP-1, and COX-2, which are known to promote osteoclastogenesis. Therefore, down-regulation of the inflammatory response of the osteoblasts brought about by breast cancer cells may reduce the activation of osteoclasts and decrease osteolysis. In this study, I took advantage of the fact that the induction of IL-6, MCP-1, COX-2 and iNOs are regulated by a common transcription factor, NF-kappaB. I hypothesized that inhibition of NF-kappaB would prevent the response to the BCCM. NF-kappaB, a crucial transcription factor, is sensitive to intracellular redox status; its activation can be inhibited by cellular antioxidant enzymes. Interestingly, two major antioxidant enzymes, glutathione peroxidase (GPxs) and thioredoxin reductase (TR), are selenoenzymes. Their dependence on selenium (Se) may offer a way to increase their expression and activity, block NF-kappaB activation and thus inhibit the expression of its target genes. I discovered that supplementation of osteoblasts with the organic Se compound, methylseleninic acid (MSA), down-regulated the inflammatory response by suppressing the activation of NF-kappaB while the supplementation of inorganic Se compound, sodium selenite, failed to reduce the inflammatory response. MSA significantly increased the activity and expression of selenoproteins in the osteoblasts. However, the suppressive effect of MSA was observed at a concentration higher than the maximum concentration for selenoprotein synthesis, which may suggest the involvement of selenium metabolites. I also found that in order to inhibit inflammatory responses, osteoblasts needed to be supplemented with MSA at the same time when they were stimulated with BCCM. This finding indicated the rapid generation and instability of the molecule responsible for the inhibition of the osteoblast inflammatory response. To test the effect of dietary selenium in breast cancer progression, three selenium supplementation diets (sodium selenite, SeM, and MSA) as well as selenium-deficient and selenium-adequate diets were fed to immunocompetent Balb/C mice before inoculation of a metastatic breast cancer cell line, 4T1.2. There was no significant difference in the development or growth of the primary breast tumor and the metastatic patterns between mice receiving the… Advisors/Committee Members: Andrea Marie Mastro, Dissertation Advisor/Co-Advisor, Andrea Marie Mastro, Committee Chair/Co-Chair, Kumble Sandeep Prabhu, Committee Member, Lorraine C Santy, Committee Member, Yanming Wang, Committee Member, Robert Paulson, Committee Member.

Subjects/Keywords: NF-kappa B; selenium; inflammatoru response; osteoblast; brreast cancer bone metastasis; MDA-MB-231; 4T1.2

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chen, Y. (2011). ORGANIC SELENIUM MODIFIES THE OSTEOBLAST INFLAMMATORY STRESS RESPONSE TO BONE METASTATIC BREAST CANCER CELLS IN VITRO AND AFFECTS BREAST CANCER PROGRESSION IN VIVO . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/12507

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chen, Yu-Chi. “ORGANIC SELENIUM MODIFIES THE OSTEOBLAST INFLAMMATORY STRESS RESPONSE TO BONE METASTATIC BREAST CANCER CELLS IN VITRO AND AFFECTS BREAST CANCER PROGRESSION IN VIVO .” 2011. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/12507.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Vancouver:

Chen Y. ORGANIC SELENIUM MODIFIES THE OSTEOBLAST INFLAMMATORY STRESS RESPONSE TO BONE METASTATIC BREAST CANCER CELLS IN VITRO AND AFFECTS BREAST CANCER PROGRESSION IN VIVO . [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/12507.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chen Y. ORGANIC SELENIUM MODIFIES THE OSTEOBLAST INFLAMMATORY STRESS RESPONSE TO BONE METASTATIC BREAST CANCER CELLS IN VITRO AND AFFECTS BREAST CANCER PROGRESSION IN VIVO . [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/12507

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

7. Xia, Mingcan. Roles of Nkg2d/ligand-mediated Immune activations in progression of metabolic dysfunctions and vascular complications.

Degree: 2012, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/13899

► Atherosclerosis (also known as arteriosclerotic vascular disease or ASVD) is a chronic inflammatory disease and characterized by patchy thickening of the inner lining of arterial… (more)

▼ Atherosclerosis (also known as arteriosclerotic vascular disease or ASVD) is a chronic inflammatory disease and characterized by patchy thickening of the inner lining of arterial walls, caused by deposits of fatty materials and infiltration of immune cell components. While the etiology of the disease is not well understood, it is commonly believed that atherosclerotic risk factors, such as hyperlipidemia and hyperglycemia, cause various cellular stress responses that induce tissue inflammation and immune cell activation, which in turn exacerbate the metabolic dysfunction. The interplay between the immune system and abnormal metabolic conditions sustains and propagates a vicious feedback cycle of chronic inflammation and metabolic dysfunction that is critical for atherosclerotic progression. However, the underlying molecular mechanisms involved in these processes are not fully understood. In this thesis study, I determined the role of NKG2D/ligand-mediated immune activation in the pathogenesis of atherosclerosis. I found that NKG2D ligands were upregulated in sera from type 2 diabetes patients. In addition, cells from human atherosclerotic lesions, including macrophage and endothelial cells exhibited a high-level expression of the NKG2D ligands. By using atherosclerotic ApoE-/- mouse models, we found upregulation of NKG2D ligands in not only atherosclerotic lesions but also other tissueswhere atherosclerosis-associated metabolites preferentially accumulated, particularly the liver, suggesting that atherosclerosis-associated metabolites might be involved in the upregulation of NKG2D ligands. Consistent with this, oxidized low-density lipoprotein (oxLDL) or advanced glycation end-products (AGE), two commonmetabolites associated with dyslipidemia and hyperglycemia, induce macrophage to express NKG2D ligands during the in vitro culture. Preventing NKG2D/ligandinteractions by either genetic NKG2D-deficiency or anti-NKG2D antibody significantly suppressed atherosclerotic lesion formation, demonstrating a critical role of the NKG2D/ligand axis in the disease progression. Blocking NKG2D/ligandinteractions reduced the systemic production of multiple cytokine markers associated with immune activation. In addition, blocking NKG2D/ligand interactions alleviated the metabolic disorder associated with the liver dysfunction in Western diet-fed NKG2D-deficient ApoE-/- mice by preventing immune activation-induced liver inflammation. Moreover, NKG2D-deficient, T/B-cell-deficient ApoE-/-mice showed delayed atherosclerotic lesion formation after Western Diet feeding, suggesting an important role of NKG2D-expressing T immune cells in the early development of atherosclerosis. My preliminary studies also found that NKG2D-mediated responses were also involved in Western Diet-induced complications in other tissues, such as the kidney. Taken together, my studies reveal that the NKG2D/ligand interaction is a critical molecular link between atherosclerosis-related chronic inflammation and metabolic dysfunction and the NKG2D/ligand mediated… Advisors/Committee Members: Na Xiong, Dissertation Advisor/Co-Advisor, Margherita Teresa Anna Cantorna, Committee Member, Pamela Hankey Giblin, Committee Member, Kumble Sandeep Prabhu, Committee Member, Yanming Wang, Committee Member, Avery August, Special Member, Na Xiong, Committee Chair/Co-Chair.

Subjects/Keywords: atherosclerosis; metabolic dysfunction; NKG2D ligand; NKG2D; Immune activation; diabetes; cardiovascular diseases; liver dysfunction

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Xia, M. (2012). Roles of Nkg2d/ligand-mediated Immune activations in progression of metabolic dysfunctions and vascular complications. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/13899

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Xia, Mingcan. “Roles of Nkg2d/ligand-mediated Immune activations in progression of metabolic dysfunctions and vascular complications.” 2012. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/13899.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Xia, Mingcan. “Roles of Nkg2d/ligand-mediated Immune activations in progression of metabolic dysfunctions and vascular complications.” 2012. Web. 19 Jan 2021.

Vancouver:

Xia M. Roles of Nkg2d/ligand-mediated Immune activations in progression of metabolic dysfunctions and vascular complications. [Internet] [Thesis]. Penn State University; 2012. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/13899.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Xia M. Roles of Nkg2d/ligand-mediated Immune activations in progression of metabolic dysfunctions and vascular complications. [Thesis]. Penn State University; 2012. Available from: https://submit-etda.libraries.psu.edu/catalog/13899

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

8. Kilpatrick, Casey Leigh. Elucidating the role of GODZ-mediated palmitoylation in controlling GABAergic inhibition .

Degree: 2016, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/28909

► Palmitoylation involves the addition of a 16-carbon fatty acid chain to cysteine residues, which increases the hydrophobicity of the target protein. This modification functionally influences… (more)

▼ Palmitoylation involves the addition of a 16-carbon fatty acid chain to cysteine residues, which increases the hydrophobicity of the target protein. This modification functionally influences membrane targeting, protein conformational state, complex formation and protein-protein interactions. Palmitoylation is a rapidly reversible and dynamically regulated post-translational modification that affects the function or localization of many neuronal proteins including GABAA receptors (GABAARs). GABAARs are heteropentameric chloride channels responsible for mediating phasic inhibitory neurotransmission in the brain. The γ2 subunit of GABAARs is critically important for trafficking of these receptors to the synapse and for normal GABAergic synaptic transmission. GABAAR γ2 heterozygous knockout mice have moderate functional deficits in GABAergic neurotransmission that result in behavioral and other alterations that are analogous to depression in humans. Diverse post-translational modifications of the γ2 subunit intracellular loop affect the membrane dynamics of GABAARs and therefore the function of inhibitory synapses. The γ2 subunit is subject to palmitoylation by Golgi-specific DHHC-type zinc finger protein (GODZ, DHHC3) and its paralog, Sertoli cell gene with a zinc finger domain (SERZ-β, DHHC7). Knockdown of GODZ by shRNA or a dominant negative construct indicated that GODZ-mediated palmitoylation regulates the accumulation of GABAARs at synapses, as well as GABAergic innervation. Neurons derived from GODZ knock-out (KO) and GODZ/SERZ-β double KO mice grown in co-culture with wild-type (WT) neurons, exhibit a loss of punctate immunostaining for presynaptic glutamate decarboxylase (GAD) and postsynaptic γ2 indicating a loss of GABAergic innervation. The loss of synapses could potentially be a result of GODZ palmitoylating other proteins involved in synapse formation and maintenance such as the postsynaptic adhesion molecule, neuroligin 2 (NL2). The main objective of this dissertation was to further elucidate the mechanism by which GODZ-mediated palmitoylation controls GABAergic inhibition in vivo, by utilizing GODZ KO mice. I screened for candidate novel substrates of GODZ using a combined acyl-biotin exchange assay and quantitative proteomics with isobaric tags for relative and absolute quantitation (iTRAQ) approach. Proteomic analyses of putative palmitoylated proteins revealed that there were a wide variety of proteins that were differentially palmitoylated or expressed in brain tissue of WT compared to GODZ KO mice. This result is consistent with previous evidence that GODZ has broad substrate specificity. Through proteomics, growth associated protein (GAP-43) was identified as a palmitoylated protein that is less abundant or less palmitoylated in brain of KO compared to WT mice. We confirmed that GAP-43 could be palmitoylated by GODZ in transfected HEK 293T cells. Moreover, steady state palmitoylation of the γ2 subunit and GAP-43 was significantly reduced in brain extracts of GODZ KO vs. WT mice,… Advisors/Committee Members: Bernhard Luscher, Dissertation Advisor/Co-Advisor, Bernhard Luscher, Committee Chair/Co-Chair, Melissa Rolls, Committee Member, Curtis John Omiecinski, Special Member, Yanming Wang, Committee Member.

Subjects/Keywords: GODZ; palmitoylation; GABA

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kilpatrick, C. L. (2016). Elucidating the role of GODZ-mediated palmitoylation in controlling GABAergic inhibition . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/28909

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kilpatrick, Casey Leigh. “Elucidating the role of GODZ-mediated palmitoylation in controlling GABAergic inhibition .” 2016. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/28909.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kilpatrick, Casey Leigh. “Elucidating the role of GODZ-mediated palmitoylation in controlling GABAergic inhibition .” 2016. Web. 19 Jan 2021.

Vancouver:

Kilpatrick CL. Elucidating the role of GODZ-mediated palmitoylation in controlling GABAergic inhibition . [Internet] [Thesis]. Penn State University; 2016. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/28909.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kilpatrick CL. Elucidating the role of GODZ-mediated palmitoylation in controlling GABAergic inhibition . [Thesis]. Penn State University; 2016. Available from: https://submit-etda.libraries.psu.edu/catalog/28909

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

9. Wang, Po-Hao. Epigenetic regulatory role and fine mapping of unstable factor for orange1 in maize.

Degree: 2012, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/15237

► Epigenetic regulation in plants plays an important role in many biological processes, such as transposon silencing, genomic imprinting, paramutation, epimutation, and transgene silencing. However, the… (more)

▼ Epigenetic regulation in plants plays an important role in many biological processes, such as transposon silencing, genomic imprinting, paramutation, epimutation, and transgene silencing. However, the detailed mechanisms are not yet fully understood. In this study, we used pericarp color1 (p1) as a genetic and phenotypic marker to study the nature of epigenetic regulation in maize. The p1 gene encodes an R2R3 Myb transcription factor and regulates biosynthesis of red phlobaphene pigments in the flavonoid pathway. Expression of the p1 gene commonly yields red pigmentation in pericarps and cob glumes, leading to diverse pigmentation patterns. More than 100 alleles of p1and their conspicuous pigmentation patterns have been reported. For instance, P1-wr confers white pericarp and red cob glume, whereas P1-rr confers red pericarp and red cob glume phenotypes. We have previously determined that P1-wr allelic pattern is epigenetically regulated. To elucidate the detailed mechanism(s) responsible for the tissue-specific silencing of P1-wr through epigenetics, reverse genetics approaches were used to isolate mutations that disrupt p1 silencing. We have thus characterized Unstable factor for orange1 (Ufo1), a trans-acting dominant epigenetic modifier. The Ufo1-1 mutation relieves P1-wr silencing and induces ectopic p1 expression in several organs including pericarp, leaf sheath, husk, and tassel glume. The increased p1 expression has been associated with reduction of DNA methylation at P1-wr. In addition to activating the pericarp expression of P1-wr allele, Ufo1-1 mutation also perturbs the pericarp and cob glume silencing of an ultra-silent P1-wr epiallele (P1-wr*). First exposure of P1-wr* to Ufo1-1 activated the p1 expression in cob glume and such activation was associated with the decrease of DNA methylation at the cob-specific regulatory element in intron 2 of the p1. In chapter 2, I demonstrated that suppression of p1 expression in pericarps is relieved subsequently after cob glume pigmentation is first restored, suggesting a sequential reactivation epigenetic mechanism. This mechanism may involve relaxation of chromatin structure because the sequential interaction of Ufo1-1 with the silent P1-wr* is associated with the reduction of H3K9me2. In addition to P1-wr*, the reduction of H3K9me2 was also observed in other Ufo1-1-induced reactivation of silent p1 alleles. iv These results suggest that wild-type ufo1 is involved in an epigenetic mechanism which is responsible for maintenance of suppressive histone marks at the silent alleles of p1. In chapter 3, I compared ufo1 with another epigenetic modifier, Mediator for paramutation1 (Mop1), for their effects in the maintenance of transcriptional silencing. The Mop1 encodes an RNA-dependent RNA polymerase and is required for establishment and maintenance of paramutation at certain maize loci. It has been shown that mop1-1 mutation gradually reactivates the silencing of p1 alleles but in contrast to the prompt reactivation of silencing in Ufo1-1 background, more than one… Advisors/Committee Members: Surinder Chopra, Dissertation Advisor/Co-Advisor, Surinder Chopra, Committee Chair/Co-Chair, Dawn S Luthe, Committee Member, Majid R Foolad, Committee Member, Yinong Yang, Committee Member, Yanming Wang, Committee Member.

Subjects/Keywords: maize; genetics; genetics; fine mapping

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wang, P. (2012). Epigenetic regulatory role and fine mapping of unstable factor for orange1 in maize. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/15237

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wang, Po-Hao. “Epigenetic regulatory role and fine mapping of unstable factor for orange1 in maize.” 2012. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/15237.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wang, Po-Hao. “Epigenetic regulatory role and fine mapping of unstable factor for orange1 in maize.” 2012. Web. 19 Jan 2021.

Vancouver:

Wang P. Epigenetic regulatory role and fine mapping of unstable factor for orange1 in maize. [Internet] [Thesis]. Penn State University; 2012. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/15237.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wang P. Epigenetic regulatory role and fine mapping of unstable factor for orange1 in maize. [Thesis]. Penn State University; 2012. Available from: https://submit-etda.libraries.psu.edu/catalog/15237

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

10. Zhu, Bokai. Modulation Of Skin Cancer By Peroxisome Proliferator-activated Receptor Beta/delta.

Degree: 2012, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/15143

► Ligand activation of peroxisome proliferator–activated receptor-β/δ (PPARβ/δ) inhibits chemically-induced skin tumorigenesis and Pparβ/δ-null mice exhibit enhanced chemically-induced skin tumorigenesis compared to wild-type mice. Since over… (more)

▼ Ligand activation of peroxisome proliferator–activated receptor-β/δ (PPARβ/δ) inhibits chemically-induced skin tumorigenesis and Pparβ/δ-null mice exhibit enhanced chemically-induced skin tumorigenesis compared to wild-type mice. Since over 90% of chemically-induced tumors contain Hras mutations, this suggests that PPARβ/δ could inhibit chemically-induced skin tumorigenesis by modulating Hras signaling, which was examined in this study. In addition, ligand activation of PPARβ/δ and inhibition of cyclooxygenase-2 (COX2) activity by nonsteroidal anti-inflammatory drugs (NSAID) can both attenuate skin tumorigenesis. The hypothesis that combining ligand activation of PPARβ/δ with inhibition of COX2 activity will increase the efficacy of chemoprevention of chemically induced skin tumorigenesis over that observed with either approach alone is also examined in this study. Ligand activation of PPARβ/δ caused a negative selection against cells expressing higher levels of HRAS by inducing a mitotic block. Mitosis-related genes that are predominantly regulated by E2F were induced to a higher level in HRAS-expressing Pparβ/δ-null keratinocytes as compared to HRAS-expressing wild-type keratinocytes. Ligand activated PPARβ/δ repressed expression of these genes by direct binding with p130/p107, facilitating nuclear translocation, and increasing promoter recruitment of p130/p107. In addition, co-treatment with a PPARβ/δ ligand and various mitosis inhibitors increases the efficacy of increasing G2/M arrest. Moreover, PPARβ/δ suppresses tumorigenesis by promoting HRAS-induced senescence. PPARβ/δ transcriptionally regulates Rasgrp1 and Ilk causing increased p-ERK and decreased p-AKT that promote HRAS-induced senescence. PPARβ/δ also promotes senescence through attenuation of HRAS-induced ER stress and ER stress-associated UPR by repressing p-AKT-mTOR signaling. Further, these studies demonstrate a novel positive feedback loop between p-AKT, ER stress and UPR. An acute increase of ER stress is sufficient to establish the positive loop, maintaining higher UPR and p-AKT activity, collectively causing evasion of senescence and malignant conversion. Moreover, increased PPARβ/δ expression and decreased ER stress correlated with increased senescence in both mouse and human tumors. Ligand activation of PPARβ/δ with GW0742 caused a PPARβ/δ-dependent delay in the onset of tumor formation. Nimesulide also delayed the onset of tumor formation and caused inhibition of tumor multiplicity in wild-type mice but not in Pparβ/δ-null mice. Combining ligand activation of PPARβ/δ with dietary nimesulide resulted in a further decrease of tumor multiplicity in wild-type mice but not in Pparβ/δ-null mice. Biochemical and molecular analysis of skin and tumor samples show that these effects were due to the modulation of terminal differentiation, attenuation of inflammatory signaling, and induction of apoptosis through both PPARβ/δ-dependent and PPARβ/δ-independent mechanisms. Increased levels and activity of PPARβ/δ by nimesulide were also observed. These… Advisors/Committee Members: Jeffrey Maurice Peters, Dissertation Advisor/Co-Advisor, Jeffrey Maurice Peters, Committee Chair/Co-Chair, Yanming Wang, Committee Member, Gary H Perdew, Committee Member, Adam Bleier Glick, Committee Member, Wendy Hanna Rose, Committee Member.

Subjects/Keywords: PPARb/d; HRAS; Mitosis; Senescence; ER stress

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zhu, B. (2012). Modulation Of Skin Cancer By Peroxisome Proliferator-activated Receptor Beta/delta. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/15143

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zhu, Bokai. “Modulation Of Skin Cancer By Peroxisome Proliferator-activated Receptor Beta/delta.” 2012. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/15143.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zhu, Bokai. “Modulation Of Skin Cancer By Peroxisome Proliferator-activated Receptor Beta/delta.” 2012. Web. 19 Jan 2021.

Vancouver:

Zhu B. Modulation Of Skin Cancer By Peroxisome Proliferator-activated Receptor Beta/delta. [Internet] [Thesis]. Penn State University; 2012. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/15143.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zhu B. Modulation Of Skin Cancer By Peroxisome Proliferator-activated Receptor Beta/delta. [Thesis]. Penn State University; 2012. Available from: https://submit-etda.libraries.psu.edu/catalog/15143

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

11. Zheng, Suting. The Many Facets of Histone Tails in Regulating Transcription .

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/12253

► In eukaryotic cells, DNA is assembled into chromatin with histone proteins. The basic subunit of chromatin is the nucleosome, which consists of 147bp of DNA… (more)

▼ In eukaryotic cells, DNA is assembled into chromatin with histone proteins. The basic subunit of chromatin is the nucleosome, which consists of 147bp of DNA wrapped around a histone octamer. The N-terminal domains of histone proteins protrude from the nucleosome surface, maintain proper chromatin structure and serve as binding site of regulatory proteins. Genome wide gene expression profiling of histone tail mutants suggested that the tails are required for both transcription activation and repression in vivo. However, the mechanisms of how histone tails regulate these events remain largely unknown. Here I explored the roles of different histone tails in gene regulation and my study provides evidence to show that different histone tails regulate distinct events at multiple stages of transcription. First, I demonstrate that deleting the H3 N terminal tails results in a shift of RNA polymerase density towards the 3’ end of gene, which indicates a defect in elongation. Further studies revealed that the H3 tail mutants severely impair H3 lysine 36 trimethylation. Recruitment of elongation factors and Set2 methyltransferase was examined and the H3 tails were dispensable for the association of these factors to genes. In vitro biochemistry assays carried out in the lab suggested that the H3 tail is critical for the catalytic activity of Set2. Thus, this novel “intra-tail” interaction added another level of regulation of Set2 activity, which in turn, controlled the dynamics of methylation during elongation. Histone modifications not only regulate transcription directly, they also regulate one another, providing crosstalk. In the second part of this study, I describe a novel “trans-tail” regulation involving the N-terminal tail of histone H2A. Deleting the N terminus of H2A reduces H2B ubiquitylation and H3K4 methylation, but does not affect the recruitment of the modifying enzymes to genes. I mapped the region primarily responsible for this regulation to the H2A Repression domain (HAR). Surprisingly, HAR locates in close proximity with H2BK123 in the nucleosome structure. Furthermore, the HAR is partially occluded by nucleosomal DNA, suggesting that the function of the H2A crosstalk pathway is to restrict histone modifications to nucleosomes altered by transcription. Appropriate gene expression requires various factors, including histone chaperones and ATP dependent chromatin remodelers, to break through the chromatin barrier and facilitate RNAP II transcription. In the third section, I provided evidence to show that a conserved region in the histone H2B tail, the H2B Repression domain (HBR), regulates the activity of FACT, a histone chaperone. Deleting HBR, or the H2B tail, impairs the interaction between FACT and H2A/H2B dimer, and hampers FACT mediated chromatin remodeling, transcription activation and the redeposition of histone following the passage of polymerase. Therefore, in addition to its reported roles in repressing transcription, my study suggests a novel function of HBR in regulating histone… Advisors/Committee Members: Joseph C. Reese, Dissertation Advisor/Co-Advisor, Joseph C. Reese, Committee Chair/Co-Chair, Benjamin Franklin Pugh, Committee Member, Yanming Wang, Committee Member, David Scott Gilmour, Committee Member, Song Tan, Committee Member, Michael Axtell, Committee Member.

Subjects/Keywords: chromatin modification; histone chaperone

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zheng, S. (2011). The Many Facets of Histone Tails in Regulating Transcription . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/12253

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zheng, Suting. “The Many Facets of Histone Tails in Regulating Transcription .” 2011. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/12253.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zheng, Suting. “The Many Facets of Histone Tails in Regulating Transcription .” 2011. Web. 19 Jan 2021.

Vancouver:

Zheng S. The Many Facets of Histone Tails in Regulating Transcription . [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/12253.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zheng S. The Many Facets of Histone Tails in Regulating Transcription . [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/12253

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

12. Deng, Yaoting. Regulation of Hippo Signaling for Growth Control.

Degree: 2014, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/23417

► In multicellular organisms, the coordination of cell proliferation, cell death and cellular growth are crucial for the organ size control and the maintenance of organ… (more)

▼ In multicellular organisms, the coordination of cell proliferation, cell death and cellular growth are crucial for the organ size control and the maintenance of organ function. The mechanisms that regulate these crucial processes provide insight into diseases, such as cancer. The Hippo (Hpo) signaling regulates cell number mainly by inhibiting cell proliferation and promoting cell apoptosis, and this signaling is highly conserved from Drosophila to mammals. Hpo is the key kinase of Hpo signaling; however, the way in which Hpo kinase activity is regulated remains less understood. In this project, I investigated how Hpo kinase is activated and regulated by upstream molecules both in vivo and in vitro. I found that Hpo dimerization could facilitate its activation by auto-phosphorylation. Moreover, membrane association appears to increase Hpo dimerization efficiency, and upstream molecules Expanded/Merlin/Kibra promote Hpo membrane association. Therefore, both dimerization and membrane association are critical for Hpo kinase to be activated. This mechanism provides essential insight to reveal the mystery that how upstream molecules transduce signal to Hpo signaling. In another project, I investigated Yap1 (a major downstream effector of mammalian Hpo signaling) activity regulation in mammalian pancreatic beta β-cells under free fatty acids (FFAs) treatment. Mammalian pancreatic β-cells are responsible for the production of insulin and therefore play a pivotal role in development and glucose homeostasis. Among many factors, high concentrations of saturated free fatty acids (FFAs) such as palmitate are known to have a negative effect on β-cell viability, which might induce type 2 diabetes. In this study, I demonstrated that Hpo signaling effector Yap1 plays a crucial role in regulating β-cell survival under FFA treatment. I found that Yap1 is activated through F-actin accumulation in a time-delayed manner to enhance β-cells viability during palmitate-induced apoptosis. Moreover, Connective Tissue Growth Factor (CTGF), one of the downstream targets of Yap1, was identified to repress palmitate-induced β-cell apoptosis. These discoveries support a model in which Yap1 could positively regulate β-cell survival under FFA treatment, and this model might lead to the development of new strategies for potential treatment of diabetes. Advisors/Committee Members: Zhi Chun Lai, Dissertation Advisor/Co-Advisor, Zhi Chun Lai, Committee Chair/Co-Chair, Melissa Rolls, Committee Member, Pamela Hankey Giblin, Committee Member, Richard W Ordway, Committee Member, Wendy Hanna Rose, Committee Member, Yanming Wang, Committee Member.

Subjects/Keywords: Hippo pathway; Hippo; transphosphorylation; dimerization; Merlin; Expanded; Kibra; FFA; β-cells; Yap; F-actin; apoptosis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Deng, Y. (2014). Regulation of Hippo Signaling for Growth Control. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/23417

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Deng, Yaoting. “Regulation of Hippo Signaling for Growth Control.” 2014. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/23417.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Deng, Yaoting. “Regulation of Hippo Signaling for Growth Control.” 2014. Web. 19 Jan 2021.

Vancouver:

Deng Y. Regulation of Hippo Signaling for Growth Control. [Internet] [Thesis]. Penn State University; 2014. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/23417.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Deng Y. Regulation of Hippo Signaling for Growth Control. [Thesis]. Penn State University; 2014. Available from: https://submit-etda.libraries.psu.edu/catalog/23417

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

13. Ghosh, Saikat Kumar Bijoy. Role of Transcription Factors in Pausing RNA Polymerase II in Drosophila.

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11692

► Promoter proximal pausing of RNA Polymerase II (Pol II) occurs on thousands of genes in animal cells. This pausing often correlates with rapid induction of… (more)

▼ Promoter proximal pausing of RNA Polymerase II (Pol II) occurs on thousands of genes in animal cells. This pausing often correlates with rapid induction of genes, but direct tests of the relationship between pausing and induction rates are lacking. Hsp70 and hsp26 in Drosophila are rapidly induced by heat shock. Contrary to current expectations, depletion of NELF, a key factor in setting up the paused Pol II, disrupted pausing but did not interfere with rapid induction. Instead, depletion of NELF delayed the time when these genes shut off during recovery from heat shock. Further analyses showed that NELF-depletion delayed the dissociation of HSF from hsp70 and hsp26, and a similar delay was observed when CBP was depleted from cells. CBP has been reported to associate with Pol II, and acetylation of HSF by CBP has been implicated in dissociating HSF from heat shock genes. I propose that NELF-mediated pausing allows Pol II to direct CBP-mediated acetylation of HSF, thus causing HSF to dissociate from the gene. Activators are typically viewed as controlling Pol II transcription. My results reveal a reciprocal relationship in which the pausing of Pol II by NELF influences the interaction of the activator. We have also observed that pausing on hsp70 can be shifted towards the transcription start site (TSS) in a cell free system by reducing the nucleotide concentration. To analyze whether the elongation rate of the Pol II affected where Pol II paused in vivo, permanganate footprinting of the salivary glands of wild type and a slow Pol II mutant polymerase was performed. My results showed that there is an upstream shift of the slower moving Pol II. This revealed that the location of NELF mediated pause is dictated by the rate of elongation, which in turn may result from the kinetic competition between the rate of elongation and the rate of binding by negative regulators. NELF also influences the expression of many genes, wherein depleting NELF down-regulated as well as up-regulated the expression of these target genes. Here I have compared using permanganate genomic mapping the effect of NELF depletion on Pol II pausing at NELF target genes in Drosophila salivary glands and tissue culture cells. This study demonstrated that Drosophila salivary glands can be used as a model tissue for investigating effects of factors regulating paused Pol II. Advisors/Committee Members: David Scott Gilmour, Dissertation Advisor/Co-Advisor, David Scott Gilmour, Committee Chair/Co-Chair, Benjamin Franklin Pugh, Committee Member, B Tracy Nixon, Committee Member, Yanming Wang, Committee Member, Pamela Hankey Giblin, Committee Member, Andrew Thomas Henderson, Committee Member.

Subjects/Keywords: Drosophila; Transcription shut-off; NELF; HSF; pausing; heat shock recovery

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ghosh, S. K. B. (2011). Role of Transcription Factors in Pausing RNA Polymerase II in Drosophila. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11692

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ghosh, Saikat Kumar Bijoy. “Role of Transcription Factors in Pausing RNA Polymerase II in Drosophila.” 2011. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/11692.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ghosh, Saikat Kumar Bijoy. “Role of Transcription Factors in Pausing RNA Polymerase II in Drosophila.” 2011. Web. 19 Jan 2021.

Vancouver:

Ghosh SKB. Role of Transcription Factors in Pausing RNA Polymerase II in Drosophila. [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/11692.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ghosh SKB. Role of Transcription Factors in Pausing RNA Polymerase II in Drosophila. [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/11692

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

14. Shang, Gao. THE DEVELOPMENT AND APPLICATIONS OF ELECTRON-RICH PHOSPHORUS-CONTAINING LIGANDS IN ASYMMETRIC HYDROGENATION.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/8189

► Catalytic asymmetric transformations are important synthetic approaches for the preparation of enantiomerically enriched products. Among numerous methodologies developed in the past few decades, transition metal-catalyzed… (more)

▼ Catalytic asymmetric transformations are important synthetic approaches for the preparation of enantiomerically enriched products. Among numerous methodologies developed in the past few decades, transition metal-catalyzed asymmetric hydrogenation has been demonstrated as one of the most efficient methods. In this particular area, two directions of research can be found. One is the exploration of unsaturated prochiral molecules that can serve as hydrogenation substrates and produce important chiral product using current available catalysts. On the other hand, the continuous development of novel chiral ligands, usually phosphorus containing ligands, also plays a key role in improving the efficiency of this methodology. It is interesting to note that an important discovery in one direction can frequently promote the studies in the other. These two directions are also the main focuses of this dissertation. From chapter 2 to chapter 4, three kinds of challenging substrates were studied in transition metal-catalyzed hydrogenation reaction and important chiral products were obtained in good yields and selectivities. In chapter 2, A highly enantioselective synthesis of arylglycine derivatives through Rh-bisphosphine catalyzed asymmetric hydrogenation is presented. The stable N-PMP protected α-aryl imino esters were synthesized from the corresponding α-ketoesters in high yields. Using a rhodium catalyst with an electron rich and rigid Rh-TangPhos, high ee values have been achieved in the hydrogenation of N-PMP protected α-aryl imino esters. An efficient Pd-bisphosphine catalyzed hydrogenation of unfunctionalized N-tosylimines is presented in chapter 3. N-tosylimines could be synthesized from corresponding ketones exclusively in E configuration and readily served as substrates for asymmetric hydrogenation. Excellent enantioselectivities (up to 99% ee) and conversions (up to >99%) could be achieved when Pd(OCOCF3)2 complexed with an electron-rich rigid chiral bisphosphine, TangPhos, was employed. A variety of aromatic, aliphatic and cyclic chiral amines can be prepared from this methodology. In chapter 4, two β-receptor agonists (-)-denopamine and (-)-arbutamine were prepared in good yields and enantioselectivities via asymmetric hydrogenation of unprotected amino ketones for the first time using Rh catalysts bearing electron-rich phosphine ligands. A series of -primary and secondary amino ketones were synthesized and hydrogenated to produce various 1,2-amino alcohols in good yields and enantioselectivies. This Rh-electron rich phosphine catalyzed asymmetric hyderogenation represents one of the most promising and convenient approaches to the asymmetric synthesis of chiral amino alcohols. Despite the high diversity of chiral phosphorus ligands and their great achievement on various transformations, most of them are extremely air sensitive. The tedious synthesis and handling procedures limit them from being widely used in industrial applications. Progress in the development of new generation of air… Advisors/Committee Members: Xumu Zhang, Committee Chair/Co-Chair, Steven M Weinreb, Committee Chair/Co-Chair, Harry R Allcock, Committee Member, Beth A Williams, Committee Member, Yanming Wang, Committee Member.

Subjects/Keywords: Asymmetric hydrogenation; Catalysis; chiral phosphorus-containing ligands

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Shang, G. (2008). THE DEVELOPMENT AND APPLICATIONS OF ELECTRON-RICH PHOSPHORUS-CONTAINING LIGANDS IN ASYMMETRIC HYDROGENATION. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8189

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Shang, Gao. “THE DEVELOPMENT AND APPLICATIONS OF ELECTRON-RICH PHOSPHORUS-CONTAINING LIGANDS IN ASYMMETRIC HYDROGENATION.” 2008. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/8189.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Shang, Gao. “THE DEVELOPMENT AND APPLICATIONS OF ELECTRON-RICH PHOSPHORUS-CONTAINING LIGANDS IN ASYMMETRIC HYDROGENATION.” 2008. Web. 19 Jan 2021.

Vancouver:

Shang G. THE DEVELOPMENT AND APPLICATIONS OF ELECTRON-RICH PHOSPHORUS-CONTAINING LIGANDS IN ASYMMETRIC HYDROGENATION. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/8189.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Shang G. THE DEVELOPMENT AND APPLICATIONS OF ELECTRON-RICH PHOSPHORUS-CONTAINING LIGANDS IN ASYMMETRIC HYDROGENATION. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8189

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

15. Missra, Anamika. BIOCHEMICAL ANALYSIS OF INTERACTIONS OF DSIF AND NELF WITH THE DROSOPHILA RNA POLYMERASE II TRANSCRIPTION ELONGATION COMPLEX.

Degree: 2010, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/10560

► NELF (Negative Elongation Factor) and DSIF (DRB sensitivity inducing factor) are involved in pausing RNA Polymerase II (Pol II) in the promoter proximal region of… (more)

▼ NELF (Negative Elongation Factor) and DSIF (DRB sensitivity inducing factor) are involved in pausing RNA Polymerase II (Pol II) in the promoter proximal region of the hsp70 gene in Drosophila, before heat shock induction. Such blocks in elongation are widespread in the Drosophila genome. However, the mechanism by which DSIF and NELF participate in setting up the paused polymerase remains unclear. I purified the Drosophila NELF complex and analyzed the interactions between DSIF, NELF, and a reconstituted Pol II elongation complex to gain insight into the mechanism of pausing. Using gel-shift analysis, I observed that DSIF and NELF associate stably with the Pol II elongation complex and a nascent transcript of length greater than 18 nucleotides is required for this association. Protein-RNA crosslinking analysis revealed that Spt5, the largest subunit of DSIF, contacts the nascent transcript as it emerges from the elongation complex, which is contrary to the existing model of promoter-proximal pausing which suggests that NELF contacts the emerging nascent transcript. These results provide a possible model by which DSIF binds the elongation complex via association with the nascent transcript and subsequently recruits NELF. Since phosphorylation of Pol II by P-TEFb is thought to inhibit the association of NELF with the elongation complex and alleviate transcription inhibition, I also analyzed the effect of P-TEFb phosphorylation on the association of NELF and DSIF. My results suggest that phosphorylation by P-TEFb may not be sufficient to dissociate NELF or relieve transcriptional inhibition by DSIF and NELF. The results and biochemical methods described in this dissertation pave the way for a biochemical analysis of promoter proximal pausing in Drosophila. Advisors/Committee Members: David Scott Gilmour, Dissertation Advisor/Co-Advisor, David Scott Gilmour, Committee Chair/Co-Chair, Joseph C. Reese, Committee Member, Katsuhiko Murakami, Committee Member, Yanming Wang, Committee Member, Kyung An Han, Committee Member.

Subjects/Keywords: gene regulation; transcription; polymerase

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Missra, A. (2010). BIOCHEMICAL ANALYSIS OF INTERACTIONS OF DSIF AND NELF WITH THE DROSOPHILA RNA POLYMERASE II TRANSCRIPTION ELONGATION COMPLEX. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/10560

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Missra, Anamika. “BIOCHEMICAL ANALYSIS OF INTERACTIONS OF DSIF AND NELF WITH THE DROSOPHILA RNA POLYMERASE II TRANSCRIPTION ELONGATION COMPLEX.” 2010. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/10560.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Missra, Anamika. “BIOCHEMICAL ANALYSIS OF INTERACTIONS OF DSIF AND NELF WITH THE DROSOPHILA RNA POLYMERASE II TRANSCRIPTION ELONGATION COMPLEX.” 2010. Web. 19 Jan 2021.

Vancouver:

Missra A. BIOCHEMICAL ANALYSIS OF INTERACTIONS OF DSIF AND NELF WITH THE DROSOPHILA RNA POLYMERASE II TRANSCRIPTION ELONGATION COMPLEX. [Internet] [Thesis]. Penn State University; 2010. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/10560.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Missra A. BIOCHEMICAL ANALYSIS OF INTERACTIONS OF DSIF AND NELF WITH THE DROSOPHILA RNA POLYMERASE II TRANSCRIPTION ELONGATION COMPLEX. [Thesis]. Penn State University; 2010. Available from: https://submit-etda.libraries.psu.edu/catalog/10560

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

16. Sharda, Daniel Richard. INDUCTION OF MACROPHAGE ARGINASE I EXPRESSION BY RON AND THE IMPLICATIONS FOR PROMOTING SYNGENEIC TUMOR GROWTH .

Degree: 2010, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/10502

► In the innate immune response, macrophages play a role as the first line of defense against microbial infection through phagocytosis and secretion of inflammatory mediators… (more)

▼ In the innate immune response, macrophages play a role as the first line of defense against microbial infection through phagocytosis and secretion of inflammatory mediators such as nitric oxide (NO) and reactive oxygen species (ROS). The adaptive immune response is primed through antigen presentation by macrophages, which then respond to T cell cytokines that further aid in the clearance of pathogenic insult. Following clearance of pathogens, macrophages downregulate the inflammatory response of both the innate and adaptive branches of immunity, and this is coupled with the upregulation of genes that promote resolution of inflammation. Macrophage regulation of inducible nitric oxide synthase and arginase I expression have long been studied as prototypic markers of classical (inflammatory) versus alternative (anti-inflammatory) macrophage activation. Dampening of classical activation by the Ron receptor tyrosine kinase in macrophages has been well characterized in the murine model of septic shock where Ron-/- mice produce elevated levels of IFNã and succumb to death while wild-type animals survive. Conversely, it has been demonstrated that the Ron receptor tips the balance of macrophage activation away from the classically activated phenotype and promotes hallmarks of alternative macrophage activation, including arginase I expression. In this dissertation, we first set out to determine the mechanism by which arginase I is regulated by Ron. We demonstrate that, while IL-4 and the ligand for the Ron receptor, MSP, both enhance arginase I expression in macrophages, MSP induction of the arginase I promoter occurs at sites independent from those induced by IL-4. MSP, but not IL-4, induces potent MAPK activation in primary macrophages and, through systematic mutagenesis, we demonstrate that induction of the arginase I promoter in response to MSP is mediated by an AP-1 binding site located 433bp upstream of the transcription start site (TSS). In contrast, IL-4 induces arginase I expression through a Stat6 site located ~2.9kb upstream of the TSS. The role of these sites in vivo in primary macrophages is supported by results from ChIP analysis demonstrating enhanced binding of Fos to the AP-1 site following MSP, but not IL-4 stimulation, and the enhanced binding of Stat6 primarily by IL-4 or to a lesser extent by MSP. These data suggest that MSP and IL-4 induce arginase I expression in macrophages by both shared and divergent mechanisms. While alternative macrophage activation of arginase I is important in altering the inflammatory response to pathogens and in promoting wound healing, tumor development hijacks elevated expression of arginase I in macrophages as a means of enhancing tumor growth. Because Ron alters the balance between classically and alternatively activated macrophages, we hypothesized that activation of Ron on macrophages would promote tumor growth by enhancing arginase I expression. Here, we find that growth of the syngeneic tumors 3LL, B16-F10, and EG.7 is reduced in Ron-/- mice. Concurrently,… Advisors/Committee Members: Pamela Hankey Giblin, Dissertation Advisor/Co-Advisor, Pamela Hankey Giblin, Committee Chair/Co-Chair, Robert Paulson, Committee Member, Adam Bleier Glick, Committee Member, K Sandeep Praubu, Committee Member, Yanming Wang, Committee Member.

Subjects/Keywords: macrophage activation; tumorigenesis; arginase; RTK; Ron; MSP; IL-4

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sharda, D. R. (2010). INDUCTION OF MACROPHAGE ARGINASE I EXPRESSION BY RON AND THE IMPLICATIONS FOR PROMOTING SYNGENEIC TUMOR GROWTH . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/10502

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sharda, Daniel Richard. “INDUCTION OF MACROPHAGE ARGINASE I EXPRESSION BY RON AND THE IMPLICATIONS FOR PROMOTING SYNGENEIC TUMOR GROWTH .” 2010. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/10502.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sharda, Daniel Richard. “INDUCTION OF MACROPHAGE ARGINASE I EXPRESSION BY RON AND THE IMPLICATIONS FOR PROMOTING SYNGENEIC TUMOR GROWTH .” 2010. Web. 19 Jan 2021.

Vancouver:

Sharda DR. INDUCTION OF MACROPHAGE ARGINASE I EXPRESSION BY RON AND THE IMPLICATIONS FOR PROMOTING SYNGENEIC TUMOR GROWTH . [Internet] [Thesis]. Penn State University; 2010. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/10502.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sharda DR. INDUCTION OF MACROPHAGE ARGINASE I EXPRESSION BY RON AND THE IMPLICATIONS FOR PROMOTING SYNGENEIC TUMOR GROWTH . [Thesis]. Penn State University; 2010. Available from: https://submit-etda.libraries.psu.edu/catalog/10502

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

17. Dutta, Arnob. UNDERSTANDING HOW DHH1 AND CCR4-NOT COMPLEX REGULATE mRNA METABOLISM IN YEAST .

Degree: 2010, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11126

► The life of mRNA begins with transcription in the nucleus and ends with destruction in the cytoplasm. Several proteins work in unison to regulate the… (more)

▼ The life of mRNA begins with transcription in the nucleus and ends with destruction in the cytoplasm. Several proteins work in unison to regulate the various stages of mRNA metabolism. The Ccr4-Not complex plays roles from the “birth” to the “death” of mRNAs. Dhh1, an evolutionarily conserved member of the DEAD box family in yeast, associates with the Ccr4-Not complex, and regulates both transcription and mRNA decay. Additionally, in response to cellular stress, Dhh1 localizes to P-bodies where it affects the destruction of mRNAs. By interacting with the translation machinery Dhh1 and its orthologs also play roles in translational repression. Further it also plays important roles in G1/S DNA damage checkpoint recovery. Given the many functions of Dhh1 in both the synthesis and decay of RNAs, this study seeks to examine the structural requirements for all of Dhh1’s functions. Biochemical analysis of Dhh1 reveals that this protein binds RNA with high affinity but displays poor ATPase activity in vitro as compared to other DEAD box helicases. By studying the biochemical activities of Dhh1, key residues involved in ATP and RNA binding, and ATP hydrolysis have been identified. Next, this study helps dissect out how inactivation of these various biochemical activities affects the functioning of Dhh1, in vivo. In vivo analysis of mutant alleles that affect the biochemical activities has revealed the important roles of ATP binding and hydrolysis in most of the functions of Dhh1. Interestingly, the weak ATPase activity of Dhh1 is in part due to extensive inter-domain interactions, disruption of which greatly enhances ATP hydrolysis. We hypothesize that Dhh1 activity is stimulated by cellular factors, which impart a tight regulation on the functioning of this very abundant helicase. The highly conserved Ccr4-Not complex has been ascribed many functions, from transcription regulation to mRNA decay. Initial studies described a role of this complex in preinitiation complex formation, but a number of studies have clearly shown Ccr4-Not mediates deadenylation of mRNAs and protein ubiquitylation in the cytoplasm. It is still not clear how Ccr4-Not regulates gene expression, and which of these functions are controlled directly by this complex. This study demonstrates that Ccr4-Not complex directly regulates RNAP II-dependent transcription elongation. Using purified Ccr4-Not complex and yeast RNAP II in an in vitro transcription system, the role of the Ccr4-Not complex in regulating transcription elongation has been studied. Studies show that the complex binds directly to the elongating RNAP II complex, which is partially dependent on the emerging transcript, and it also makes contacts with the emerging transcript. Using transcription run on assays, Ccr4-Not is shown to stimulate the resumption of elongation from paused RNAP II elongation complexes. Further, Ccr4-Not works co-operatively with positive elongation factor TFIIS to stimulate elongation through transcription blocks. The in vitro results are substantiated by in vivo… Advisors/Committee Members: Joseph C. Reese, Dissertation Advisor/Co-Advisor, Joseph C. Reese, Committee Chair/Co-Chair, David Scott Gilmour, Committee Member, Craig Eugene Cameron, Committee Member, Yanming Wang, Committee Member, Philip C. Bevilacqua, Committee Member.

Subjects/Keywords: transcription; mRNA

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dutta, A. (2010). UNDERSTANDING HOW DHH1 AND CCR4-NOT COMPLEX REGULATE mRNA METABOLISM IN YEAST . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11126

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Dutta, Arnob. “UNDERSTANDING HOW DHH1 AND CCR4-NOT COMPLEX REGULATE mRNA METABOLISM IN YEAST .” 2010. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/11126.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Dutta, Arnob. “UNDERSTANDING HOW DHH1 AND CCR4-NOT COMPLEX REGULATE mRNA METABOLISM IN YEAST .” 2010. Web. 19 Jan 2021.

Vancouver:

Dutta A. UNDERSTANDING HOW DHH1 AND CCR4-NOT COMPLEX REGULATE mRNA METABOLISM IN YEAST . [Internet] [Thesis]. Penn State University; 2010. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/11126.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Dutta A. UNDERSTANDING HOW DHH1 AND CCR4-NOT COMPLEX REGULATE mRNA METABOLISM IN YEAST . [Thesis]. Penn State University; 2010. Available from: https://submit-etda.libraries.psu.edu/catalog/11126

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

18. Kruk, Jennifer Ann. The Ccr4-Not complex regulates transcription elongation and chromatin modifications.

Degree: 2010, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11250

► Although the Ccr4-Not complex regulates an array of cellular activities that control gene expression, its function in transcription initiation and elongation remain unclear. Described many… (more)

▼ Although the Ccr4-Not complex regulates an array of cellular activities that control gene expression, its function in transcription initiation and elongation remain unclear. Described many years ago as a potential regulator of pre-initiation complex (PIC) formation, it was more recently shown to be predominantly cytoplasmic, regulating mRNA degradation through multiple mechanisms. The opposing roles of the complex in transcription and mRNA decay provide a challenge for interpreting the true function of the Ccr4-Not complex. Our goal from the studies described below is to provide a comprehensive analysis of how Ccr4-Not contributes to gene expression and to clarify any misconceptions about its role in transcription. Our studies regarding Ccr4-Not’s function in transcription, regulation of chromatin structure, and genome-wide expression profiles ultimately converge to produce our working model. A direct role of this complex in transcription has not been clearly demonstrated. Here we establish the Ccr4-Not complex as a positive elongation factor, which promotes elongation through direct interactions with RNA polymerase II (RNAPII). We show Ccr4-Not is targeted to gene promoters in a transcription-dependent manner and remains associated throughout the body of the gene, likely “traveling” with elongating RNAPII. In vivo and in vitro studies confirm a direct interaction between Ccr4-Not and RNAPII, which is independent of the C-terminal domain (CTD) of RNAPII’s largest subunit, Rpb1. We find that multiple subunits of the complex are required to promote elongation by RNAPII across the gene, and deletion of these subunits results in a “piling up” of RNAPII. This phenotype suggests RNAPII may be unable to progress through transcriptional blocks, such as those caused by negative elongation factors and/or DNA-bound proteins, like nucleosomes. We additionally monitored the “last round” of RNAPII transcription through the gene following repression and observed that deletion of Ccr4-Not subunits results in a delayed run-off of RNAPII compared to wild type. Taken together, our studies establish Ccr4-Not as a positive elongation factor and suggest a model that requires Ccr4-Not for resumption of elongation following a pause. Our second focus was to characterize Ccr4-Not’s role in maintaining and resetting chromatin structure during transcription. Previous studies have identified a role for the NOT genes in regulation of histone modifications. Our results agree with the published reports, showing that deletion of NOT4 or NOT5 leads to significantly reduced levels of histone H3 lysine 4 trimethylation (H3K4me3). However, we additionally show that Ccr4, likely functioning with or parallel to the chromatin remodeling factor Isw1, collaborates to maintain the proper distribution of H3K4me3, a hallmark of active transcription. To conclude our assessment of the Ccr4-Not complex, we analyzed the gene expression profiles of multiple Ccr4-Not subunits, with the hope of identifying transcription patterns of the complex as a… Advisors/Committee Members: Joseph C. Reese, Dissertation Advisor/Co-Advisor, Joseph C. Reese, Committee Chair/Co-Chair, Craig Eugene Cameron, Committee Member, David Scott Gilmour, Committee Member, Benjamin Franklin Pugh, Committee Member, Liwang Cui, Committee Member, Yanming Wang, Committee Member.

Subjects/Keywords: Ccr4-Not; chromatin; transcription; histone methylation; elongation; RNAPII

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kruk, J. A. (2010). The Ccr4-Not complex regulates transcription elongation and chromatin modifications. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11250

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kruk, Jennifer Ann. “The Ccr4-Not complex regulates transcription elongation and chromatin modifications.” 2010. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/11250.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kruk, Jennifer Ann. “The Ccr4-Not complex regulates transcription elongation and chromatin modifications.” 2010. Web. 19 Jan 2021.

Vancouver:

Kruk JA. The Ccr4-Not complex regulates transcription elongation and chromatin modifications. [Internet] [Thesis]. Penn State University; 2010. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/11250.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kruk JA. The Ccr4-Not complex regulates transcription elongation and chromatin modifications. [Thesis]. Penn State University; 2010. Available from: https://submit-etda.libraries.psu.edu/catalog/11250

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

19. Li, Pingxin. ANALYSIS OF PEPTIDYLARGININE DEIMINASE 4 AND HISTONE CITRULLINATION IN TRANSCRIPTIONAL REGULATION AND INNATE IMMUNITY.

Degree: 2010, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11096

► Peptidylarginine deiminase 4 is an enzyme capable of converting both histone arginine and monomethyl-arginine residues into citrulline through reactions termed deimination/citrullination or demethylimination to regulate… (more)

▼ Peptidylarginine deiminase 4 is an enzyme capable of converting both histone arginine and monomethyl-arginine residues into citrulline through reactions termed deimination/citrullination or demethylimination to regulate histone arginine methylation. This histone posttranslational modification has been related to transcriptional regulation. This dissertation first investigated the role of PAD4 and PAD4 catalyzed histone citrullination in the transcriptional repression of p53-target genes, such as p21/CIP1/WAF1. PAD4 is recruited to the p53-target gene promoter in a p53-dependent manner. Paused RNA Pol II and PAD4 are detected at the p21 promoter before UV irradiation, while RNA Pol II activity and PAD4 association at the p21 promoter are dynamically regulated after UV irradiation. We also detected that PAD4 and histone citrullination coordinate with HDAC2 that mediates histone lysine deacetylation in repressing tumor suppressor gene expression. PAD4 and HDAC2 associated with p21 promoter simultaneously, and both dissociated from several p53-target gene promoters after DNA damage. Our data further revealed that PAD4 promoter association and histone citrullination level are dependent on both p53 and HDAC activity, but HDAC2 promoter association and histone Lys acetylation level are only slightly affected by p53 and PAD4 activity. PAD4 inhibitor Cl-amidine and HDAC inhibitor SAHA induced p53-target gene expression and inhibited cancer cell growth additively in a p53-dependent manner. Using knockout PAD4 mice as a genetic model, we found that PAD4 knockout mice cannot form neutrophil extracellular traps, which are highly decondensed chromatin structures that are important in fighting against invading pathogens after stimulated with chemokines and bacteria. These PAD4 knockout mice are more susceptible to bacterial infection due to the lack of NET-mediated anti-bacterial ability, suggesting an essential role of PAD4 and histone citrullination in innate immunity. Advisors/Committee Members: Yanming Wang, Dissertation Advisor/Co-Advisor, Yanming Wang, Committee Member, David Scott Gilmour, Committee Chair/Co-Chair, Zhi Chun Lai, Committee Member, Joseph C. Reese, Committee Member, Robert Paulson, Committee Member.

Subjects/Keywords: Peptidylarginine Deiminase 4; Histone Citrullination; p53; p21; Histone Deacetylase 2; Neutrophil Extracellular Traps

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Li, P. (2010). ANALYSIS OF PEPTIDYLARGININE DEIMINASE 4 AND HISTONE CITRULLINATION IN TRANSCRIPTIONAL REGULATION AND INNATE IMMUNITY. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11096

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Li, Pingxin. “ANALYSIS OF PEPTIDYLARGININE DEIMINASE 4 AND HISTONE CITRULLINATION IN TRANSCRIPTIONAL REGULATION AND INNATE IMMUNITY.” 2010. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/11096.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Li, Pingxin. “ANALYSIS OF PEPTIDYLARGININE DEIMINASE 4 AND HISTONE CITRULLINATION IN TRANSCRIPTIONAL REGULATION AND INNATE IMMUNITY.” 2010. Web. 19 Jan 2021.

Vancouver:

Li P. ANALYSIS OF PEPTIDYLARGININE DEIMINASE 4 AND HISTONE CITRULLINATION IN TRANSCRIPTIONAL REGULATION AND INNATE IMMUNITY. [Internet] [Thesis]. Penn State University; 2010. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/11096.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Li P. ANALYSIS OF PEPTIDYLARGININE DEIMINASE 4 AND HISTONE CITRULLINATION IN TRANSCRIPTIONAL REGULATION AND INNATE IMMUNITY. [Thesis]. Penn State University; 2010. Available from: https://submit-etda.libraries.psu.edu/catalog/11096

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

20. Ye, Xin. GROWTH CONTROL BY HIPPO AND AKT SIGNALING PATHWAYS IN DROSOPHILA MELANOGASTER.

Degree: 2010, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11012

► ABSTRACT Coordinated cell proliferation, cell growth and cell death are required to control normal organ size in multicellular organisms. The perturbations of the mechanisms that… (more)

Subjects/Keywords: growth control; Hippo; Akt; Drosophila

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ye, X. (2010). GROWTH CONTROL BY HIPPO AND AKT SIGNALING PATHWAYS IN DROSOPHILA MELANOGASTER. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11012

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ye, Xin. “GROWTH CONTROL BY HIPPO AND AKT SIGNALING PATHWAYS IN DROSOPHILA MELANOGASTER.” 2010. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/11012.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ye, Xin. “GROWTH CONTROL BY HIPPO AND AKT SIGNALING PATHWAYS IN DROSOPHILA MELANOGASTER.” 2010. Web. 19 Jan 2021.

Vancouver:

Ye X. GROWTH CONTROL BY HIPPO AND AKT SIGNALING PATHWAYS IN DROSOPHILA MELANOGASTER. [Internet] [Thesis]. Penn State University; 2010. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/11012.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ye X. GROWTH CONTROL BY HIPPO AND AKT SIGNALING PATHWAYS IN DROSOPHILA MELANOGASTER. [Thesis]. Penn State University; 2010. Available from: https://submit-etda.libraries.psu.edu/catalog/11012

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

21. Borland, Michael Gregory. PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR BETA/DELTA MODULATES ARYL HYDROCARBON RECEPTOR-DEPENDENT SIGNALING AND SKIN CARCINOGENESIS.

Degree: 2010, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11381

► Since its identification in the early 1990fs, the physiological roles of the nuclear hormone receptor peroxisome proliferator-activated receptor-ƒÀ/ƒÂ (PPARƒÀ/ƒÂ) have become better understood. This ligand-activated… (more)

▼ Since its identification in the early 1990fs, the physiological roles of the nuclear hormone receptor peroxisome proliferator-activated receptor-ƒÀ/ƒÂ (PPARƒÀ/ƒÂ) have become better understood. This ligand-activated transcription factor is known to be a key regulator of glucose and lipid homeostasis. PPARƒÀ/ƒÂ exhibits markedly higher expression in epithelial tissues such as the skin; therefore, this nuclear receptor been investigated in skin tumorigenesis. Most evidence has suggested that ligand activation of PPARƒÀ/ƒÂ inhibits skin tumorigenesis, and the results of mechanistic studies have established that these effects are due to receptor-dependent alterations in tumor promotion. The studies within this dissertation examined if PPARƒÀ/ƒÂ modulates another critical component of carcinogenesis, namely tumor initiation, and sought to delineate if PPARƒÀ/ƒÂ modulates the balance between carcinogen bioactivation and detoxification. Utilizing in vivo and in vitro mouse and human skin models, it was observed that PparƒÀ/ƒÂ-null mice exhibited reduced cytochrome P450 (Cyp) mRNA induction in response to polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (B[a]P) and 7,12-dimethylbenz[a]anthracene (DMBA). Cyp mRNA induction was also found to be attenuated in PparƒÀ/ƒÂ-null keratinocytes at multiple times and with eleven different PAHs. Furthermore, results generated from a PPARƒÀ/ƒÂ shRNA model in human keratinocytes revealed a similar attenuation of PAH-mediated Cyp mRNA induction. Additionally, experimental results with mouse keratinocytes indicated that PAH-mediated phase II enzyme mRNA induction is reduced in PparƒÀ/ƒÂ-null keratinocytes. The aryl hydrocarbon receptor (AHR) is the known transcriptional regulator of PAH-dependent phase I and II enzyme mRNA induction. Therefore, subsequent studies were designed to delineate how PPARƒÀ/ƒÂ modulates AHR-dependent signaling in mouse and human keratinocytes. Data generated from mechanistic studies indicated that the expression of AHR and several accessory proteins were not altered by PPARƒÀ/ƒÂ expression. The ability of AHR to bind a ligand and translocate to the nucleus were also not modulated in a PPARƒÀ/ƒÂ-dependent manner. Additionally, PPARƒÀ/ƒÂ did not appear to physically interact with the AHR. Surprisingly, PparƒÀ/ƒÂ-null keratinocytes exhibited lower AHR occupancy and histone acetylation at the Cyp1a1 promoter in response to B[a]P, as assessed by chromatin immunoprecipitation (ChIP). These findings suggested that the chromatin structure of xenobiotic metabolism promoters may be modulated by PPARƒÀ/ƒÂ. Since DNA methylation is a common method of altering chromatin structure, this mechanism of gene regulation was examined using DNA methylation inhibitors and bisulfite sequencing. Interestingly, methylation within the Cyp1a1 promoter was enhanced in PparƒÀ/ƒÂ-null keratinocytes. Additionally, inhibition of DNA methylation resulted in a PPARƒÀ/ƒÂ-dependent modulation of basal Cyp mRNA expression. These results suggest that epigenetic regulation by PPARƒÀ/ƒÂ… Advisors/Committee Members: Jeffrey Maurice Peters, Dissertation Advisor/Co-Advisor, Jeffrey Maurice Peters, Committee Chair/Co-Chair, Gary H Perdew, Committee Member, Andrea Marie Mastro, Committee Member, Yanming Wang, Committee Member, Craig Richard Baumrucker, Committee Member.

Subjects/Keywords: PPARBeta/Delta; AHR; PAH; Bioactivation; Skin carcinogenesis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Borland, M. G. (2010). PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR BETA/DELTA MODULATES ARYL HYDROCARBON RECEPTOR-DEPENDENT SIGNALING AND SKIN CARCINOGENESIS. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11381

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Borland, Michael Gregory. “PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR BETA/DELTA MODULATES ARYL HYDROCARBON RECEPTOR-DEPENDENT SIGNALING AND SKIN CARCINOGENESIS.” 2010. Thesis, Penn State University. Accessed January 19, 2021. https://submit-etda.libraries.psu.edu/catalog/11381.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Borland, Michael Gregory. “PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR BETA/DELTA MODULATES ARYL HYDROCARBON RECEPTOR-DEPENDENT SIGNALING AND SKIN CARCINOGENESIS.” 2010. Web. 19 Jan 2021.

Vancouver:

Borland MG. PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR BETA/DELTA MODULATES ARYL HYDROCARBON RECEPTOR-DEPENDENT SIGNALING AND SKIN CARCINOGENESIS. [Internet] [Thesis]. Penn State University; 2010. [cited 2021 Jan 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/11381.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Borland MG. PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR BETA/DELTA MODULATES ARYL HYDROCARBON RECEPTOR-DEPENDENT SIGNALING AND SKIN CARCINOGENESIS. [Thesis]. Penn State University; 2010. Available from: https://submit-etda.libraries.psu.edu/catalog/11381

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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