subject:(BAF57)

Cornell University

1. Hah, Nasun. Signal Regulated Gene Expression: Defining The Effects Of Estrogen Signaling Through Genomic And Proteomic Analyses.

Degree: PhD, Biochemistry, 2011, Cornell University

URL: http://hdl.handle.net/1813/33589

► Estrogens play crucial roles in regulating gene expression in physiological and disease states. Estrogens acts through estrogen receptors (ERs) and their binding sites in genomic… (more)

▼ Estrogens play crucial roles in regulating gene expression in physiological and disease states. Estrogens acts through estrogen receptors (ERs) and their binding sites in genomic DNA to modulate transcription by RNA polymerase II. Although recent gene-specific and genomic analyses have provided considerable information about of estrogen-dependent transcription, many aspects of the estrogen signaling network have not yet been elucidated. The goal of my studies was to uncover new information about the immediate and direct effects of estrogen signaling at the cell membrane, in the cytoplasm, and in the nucleus to elucidate the underlying regulatory networks. First, I investigated an ER transcriptional coregulators, SWI/SNF, an ATPdependent chromatin remodeling complex. I explored the molecular functions of the BAF57 and BAF180 subunits of SWI/SNF using a quantitative proteomic approach called SILAC (Stable Isotope Labeling by Amino Acids in Cell Culture). I found that depletion of BAF57 results in a significant depletion of BAF180 from the SWI/SNF complex without decreasing the total cellular BAF180 levels, resulting in an accumulation of cells in the G2/M phase. Knockdown of BAF57 also causes transcriptional misregulation of cell cycle-related genes involved in the late G2 checkpoint. Collectively, these studies have elucidated the role of BAF57 and BAF180 in the transcriptional control of cell proliferation. Second, I have used GRO-Seq (Global Nuclear Run-On and Massively Parallel Sequencing) to explore the immediate effects of estrogen signaling on the transcriptome of breast cancer cells. I found that estrogen directly regulates a strikingly large fraction of the transcriptome in a rapid, robust, and unexpectedly transient manner. In addition to protein coding genes, estrogen regulates the distribution and activity of all three RNA polymerases, and virtually every class of non-coding RNA that has been described to date. I also identified a large number of previously undetected estrogen-regulated intergenic transcripts, many of which are found proximal to ER[alpha] binding sites. These results provide the most comprehensive measurement of the primary and immediate estrogen effects to date. I expect that genome-wide inferences based on the direct estrogen-regulated transcriptome in combination with estrogen-regulated signaling pathway will be useful for understanding estrogen biology. Advisors/Committee Members: Kraus, William Lee (chair), Collins, Ruth N. (committee member), Lis, John T (committee member).

Subjects/Keywords: estrogen; estrogen receptor; GRO-seq; swi/snf; baf57; baf180; silac; proteomic; enhancer; edc; estrogen signaling

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

APA (6^th Edition):

Hah, N. (2011). Signal Regulated Gene Expression: Defining The Effects Of Estrogen Signaling Through Genomic And Proteomic Analyses. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/33589

Chicago Manual of Style (16^th Edition):

Hah, Nasun. “Signal Regulated Gene Expression: Defining The Effects Of Estrogen Signaling Through Genomic And Proteomic Analyses.” 2011. Doctoral Dissertation, Cornell University. Accessed February 26, 2021. http://hdl.handle.net/1813/33589.

MLA Handbook (7^th Edition):

Hah, Nasun. “Signal Regulated Gene Expression: Defining The Effects Of Estrogen Signaling Through Genomic And Proteomic Analyses.” 2011. Web. 26 Feb 2021.

Vancouver:

Hah N. Signal Regulated Gene Expression: Defining The Effects Of Estrogen Signaling Through Genomic And Proteomic Analyses. [Internet] [Doctoral dissertation]. Cornell University; 2011. [cited 2021 Feb 26]. Available from: http://hdl.handle.net/1813/33589.

Council of Science Editors:

Hah N. Signal Regulated Gene Expression: Defining The Effects Of Estrogen Signaling Through Genomic And Proteomic Analyses. [Doctoral Dissertation]. Cornell University; 2011. Available from: http://hdl.handle.net/1813/33589

2. Faralli, Hervé. Tshz3 un marqueur des cellules satellites : une étude de sa fonction dans la régulation de la myogenèse chez la souris : Tshz3 a marker of Satellite cells : study of his role in the regulation of mouse myogenesis.

Degree: Docteur es, Biologie des eucaryotes, 2010, Aix-Marseille 2

URL: http://www.theses.fr/2010AIX22045

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L’unité cellulaire du muscle squelettique est la myofibre, un syncytium hautement spécialisé générant la contraction musculaire. Au cours de la croissance et de la régénération… (more)

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L’unité cellulaire du muscle squelettique est la myofibre, un syncytium hautement spécialisé générant la contraction musculaire. Au cours de la croissance et de la régénération musculaire, les cellules satellites quiescentes (cellules souches) du muscle squelettique adulte sont activées, prolifèrent puis fusionnent formant de nouvelles fibres. A l’aide d’un modèle murin de régénération et de cultures primaires, j’ai identifié TSHZ3 comme un nouveau marqueur des cellules satellites quiescentes et activées. Dans la lignée cellulaire C2C12, j’ai mis en évidence un effet répresseur spécifique de Tshz3 sur la différenciation myogénique. L’entrée des myoblastes dans la voie de différenciation terminale est déclenchée par le facteur Myogenin (MYOG). L’activation de la transcription du gène myogenin (Myog) est dépendante du facteur MYOD et fait intervenir le complexe de remodelage de la chromatine SWI/SNF. In vitro, TSHZ3 interagit avec BAF57 une sous unité du complexe SWI/SNF. TSHZ3 réprime l’activation dépendante de MYOD sur le promoteur proximal de Myog et cette répression dépend en partie de la présence de BAF57. L’activité répressive et la cinétique d’expression de Tshz3, indique que TSHZ3 pourrait empêcher l’activation prématurée du promoteur Myog lors de la prolifération des cellules satellites activées. TSHZ3 pourrait ainsi participer aux mécanismes de régulation permettant de contrôler l’équilibre entre prolifération, différenciation et renouvellement des progéniteurs myogéniques.

Skeletal muscles are made of several units called myofibers, a syncitium into which muscular contraction is generated. During the muscle growth and repair, the quiescent Satellite Cells (SCs; adult stem cells) become activated, proliferate and differentiate to form new multinucleated myofibers. In animal model and primary culture, I found that, Tshz3 was strongly expressed in the quiescent and activated satellite cells.In C2C12 myoblast cells, I showed a specific repressive effect of TSHZ3 on the myogenic differentiation. The terminal differentiation of the myoblastes is trigger by Myogenin (Myog). The transcriptional activation of Myog promoter involves MYOD and the SWI/SNF remodelling complex. In vitro, I showed that TSHZ3 interacts with BAF57, a subunit of the SWI/SNF complex. TSHZ3 represses the MYOD-dependant activation on the Myog promoter. This specific repression involves in part BAF57.The repressive activity of and the temporal dynamic of expression of Tshz3, indicated that TSHZ3 potentially is required to impede the premature activation of the Myog promotor during the SCs proliferation. These results suggest that TSHZ3 plays important roles in the molecular mechanisms operating in activated SCs when there are poised between proliferation, differentiation and self renewal of muscular progenitors.

Advisors/Committee Members: Fasano, Laurent (thesis director), Caubit, Xavier (thesis director).

Subjects/Keywords: Muscle squelettique; Cellules satellites; Développement; Régénération; Tshz3; MyoD; Myog; Baf57; Swi/snf

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

APA (6^th Edition):

Faralli, H. (2010). Tshz3 un marqueur des cellules satellites : une étude de sa fonction dans la régulation de la myogenèse chez la souris : Tshz3 a marker of Satellite cells : study of his role in the regulation of mouse myogenesis. (Doctoral Dissertation). Aix-Marseille 2. Retrieved from http://www.theses.fr/2010AIX22045

Chicago Manual of Style (16^th Edition):

Faralli, Hervé. “Tshz3 un marqueur des cellules satellites : une étude de sa fonction dans la régulation de la myogenèse chez la souris : Tshz3 a marker of Satellite cells : study of his role in the regulation of mouse myogenesis.” 2010. Doctoral Dissertation, Aix-Marseille 2. Accessed February 26, 2021. http://www.theses.fr/2010AIX22045.

MLA Handbook (7^th Edition):

Faralli, Hervé. “Tshz3 un marqueur des cellules satellites : une étude de sa fonction dans la régulation de la myogenèse chez la souris : Tshz3 a marker of Satellite cells : study of his role in the regulation of mouse myogenesis.” 2010. Web. 26 Feb 2021.

Vancouver:

Faralli H. Tshz3 un marqueur des cellules satellites : une étude de sa fonction dans la régulation de la myogenèse chez la souris : Tshz3 a marker of Satellite cells : study of his role in the regulation of mouse myogenesis. [Internet] [Doctoral dissertation]. Aix-Marseille 2; 2010. [cited 2021 Feb 26]. Available from: http://www.theses.fr/2010AIX22045.

Council of Science Editors:

Faralli H. Tshz3 un marqueur des cellules satellites : une étude de sa fonction dans la régulation de la myogenèse chez la souris : Tshz3 a marker of Satellite cells : study of his role in the regulation of mouse myogenesis. [Doctoral Dissertation]. Aix-Marseille 2; 2010. Available from: http://www.theses.fr/2010AIX22045

3. LINK, KEVIN A. BAF57 MODULATION OF ANDROGEN RECEPTOR ACTION AND PROSTATE CANCER PROGRESSION.

Degree: PhD, Medicine : Cell and Molecular Biology, 2008, University of Cincinnati

URL: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1198854849

► Prostate cancer relies on androgens for growth and survival. Androgens elicit their function primarily through the androgen receptor (AR), a transcription factor that is required… (more)

▼ Prostate cancer relies on androgens for growth and survival. Androgens elicit their function primarily through the androgen receptor (AR), a transcription factor that is required for the development and progression of prostate cancer. Therefore, current treatment options for disseminated disease are aimed at either inhibiting androgen synthesis or preventing activation of the receptor. These treatment options are initially effective; however, recurrent disease ultimately arises within two to three years that typically present as therapy resistant. From this, it is obvious that more effective means of targeting this pathway are necessary to treat prostate cancer. The present study exploited a specific aspect of the AR activation pathway and uncovered a novel means for potentially targeting AR action and subsequent prostate cancer proliferation. The SWI/SNF chromatin remodeling complex is one such necessary component involved in mediating AR activation. Specifically, the BRM core ATPase was demonstrated to exhibit a preferential response to activating AR target genes which was dependent on promoter context. Subsequent studies identified the BAF57 subunit of the SWI/SNF complex as the primary interacting AR subunit, thus indicating a possible role in complex recruitment to AR target DNA. BAF57 proved to be critical for AR mediated transcriptional activation, AR enhanced coactivator activation, and prostate cancer proliferation. Based on these findings, the potential for targeting BAF57 as a prostate cancer therapeutic option was examined. First, expression of BAF57 was verified in human prostate tissue specimens, with possible enhanced expression observed in metastatic samples. Subsequent molecular analyses determined that the primary region of interaction occurred between the DBD/hinge region of AR and the proline-rich/HMG domain of BAF57. The N-terminal binding region of BAF57 was then shown to reduce AR recruitment to AR target genes, inhibit AR target gene activity, and decrease prostate cancer cell proliferation. Together, the data herein establish the SWI/SNF chromatin remodeling complex, specifically BAF57, as a valid target for the treatment of prostate cancer. Advisors/Committee Members: Knudsen, Dr. Karen (Advisor).

Subjects/Keywords: Biology, Molecular; prostate cancer; androgen receptor; BAF57; SWI/SNF

…BAF57 Modulation of Androgen Receptor Action and Prostate Cancer Progression A… …genes which was dependent on promoter context. Subsequent studies identified the BAF57 subunit… …role in complex recruitment to AR target DNA. BAF57 proved to be critical for AR mediated… …on these findings, the potential for targeting BAF57 as a prostate cancer therapeutic… …option was examined. First, expression of BAF57 was verified in human prostate tissue specimens…

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

APA (6^th Edition):

LINK, K. A. (2008). BAF57 MODULATION OF ANDROGEN RECEPTOR ACTION AND PROSTATE CANCER PROGRESSION. (Doctoral Dissertation). University of Cincinnati. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=ucin1198854849

Chicago Manual of Style (16^th Edition):

LINK, KEVIN A. “BAF57 MODULATION OF ANDROGEN RECEPTOR ACTION AND PROSTATE CANCER PROGRESSION.” 2008. Doctoral Dissertation, University of Cincinnati. Accessed February 26, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1198854849.

MLA Handbook (7^th Edition):

LINK, KEVIN A. “BAF57 MODULATION OF ANDROGEN RECEPTOR ACTION AND PROSTATE CANCER PROGRESSION.” 2008. Web. 26 Feb 2021.

Vancouver:

LINK KA. BAF57 MODULATION OF ANDROGEN RECEPTOR ACTION AND PROSTATE CANCER PROGRESSION. [Internet] [Doctoral dissertation]. University of Cincinnati; 2008. [cited 2021 Feb 26]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1198854849.

Council of Science Editors:

LINK KA. BAF57 MODULATION OF ANDROGEN RECEPTOR ACTION AND PROSTATE CANCER PROGRESSION. [Doctoral Dissertation]. University of Cincinnati; 2008. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1198854849

4. Sethuraman, Aarti. Role of SMARCE1 and BHLHE40 in Breast Cancer Metastasis.

Degree: PhD, Biomedical Sciences, 2018, University of Tennessee Health Science Center

URL: https://dc.uthsc.edu/dissertations/454

Subjects/Keywords: BHLHE40 / DEC1; Breast cancer metastasis; HBEGF; HIF1A; PTK2 / FAK; SMARCE1 / BAF57; Biological Phenomena, Cell Phenomena, and Immunity; Diseases; Medical Cell Biology; Medical Molecular Biology; Medical Sciences; Medicine and Health Sciences; Neoplasms

Record Details Similar Records Cite « Share

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

APA (6^th Edition):

Sethuraman, A. (2018). Role of SMARCE1 and BHLHE40 in Breast Cancer Metastasis. (Doctoral Dissertation). University of Tennessee Health Science Center. Retrieved from https://dc.uthsc.edu/dissertations/454

Chicago Manual of Style (16^th Edition):

Sethuraman, Aarti. “Role of SMARCE1 and BHLHE40 in Breast Cancer Metastasis.” 2018. Doctoral Dissertation, University of Tennessee Health Science Center. Accessed February 26, 2021. https://dc.uthsc.edu/dissertations/454.

MLA Handbook (7^th Edition):

Sethuraman, Aarti. “Role of SMARCE1 and BHLHE40 in Breast Cancer Metastasis.” 2018. Web. 26 Feb 2021.

Vancouver:

Sethuraman A. Role of SMARCE1 and BHLHE40 in Breast Cancer Metastasis. [Internet] [Doctoral dissertation]. University of Tennessee Health Science Center; 2018. [cited 2021 Feb 26]. Available from: https://dc.uthsc.edu/dissertations/454.

Council of Science Editors:

Sethuraman A. Role of SMARCE1 and BHLHE40 in Breast Cancer Metastasis. [Doctoral Dissertation]. University of Tennessee Health Science Center; 2018. Available from: https://dc.uthsc.edu/dissertations/454

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