Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for +publisher:"Cornell University" +contributor:("Kraus, William Lee"). Showing records 1 – 2 of 2 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


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

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

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

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

APA (6th 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 (16th Edition):

Hah, Nasun. “Signal Regulated Gene Expression: Defining The Effects Of Estrogen Signaling Through Genomic And Proteomic Analyses.” 2011. Doctoral Dissertation, Cornell University. Accessed January 19, 2021. http://hdl.handle.net/1813/33589.

MLA Handbook (7th Edition):

Hah, Nasun. “Signal Regulated Gene Expression: Defining The Effects Of Estrogen Signaling Through Genomic And Proteomic Analyses.” 2011. Web. 19 Jan 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 Jan 19]. 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


Cornell University

2. Frizzell, Kristine. Mechanisms Of Transcriptional Regulation By Proteins In The Nad+ Metabolic Pathway.

Degree: PhD, Biochemistry, 2011, Cornell University

Poly(ADP-ribosyl)ation (PARylation) is an enzymatic reaction whereby ADPribose units from donor NAD+ molecules are covalently attached onto target proteins. The regulation of this reaction is overseen by two nuclear enzymes, Poly(ADP-ribose) polymerase-1 (PARP-1) and poly(ADP-ribose) glycohydrolase (PARG), that modify target proteins in the nucleus by the addition and removal, respectively, of ADP-ribose polymers. While PARP-1 has generally been studied with respect to its role in DNA damage repair and cell death pathways, recent studies have revealed a role for PARP-1 in transcriptional regulation. The role of PARG in transcriptional regulation, however, is less characterized. In this study, I have investigated the coordinate patterns of gene regulation by PARP-1 and PARG in vivo using genomic and gene-specific analyses. Specifically, I show that PARP-1 and PARG coordinately regulate global patterns of gene expression by affecting genes in the same direction and with similar magnitudes. Further analysis revealed that PARP-1 and PARG localized to the promoters of both positively and negatively regulated target genes in parallel binding patterns. I also show that PARP-1 and PARG enzymatic activities are required for some, but not all, target genes. My results indicate that PARP-1 and PARG, two nuclear enzymes with opposing enzymatic activities, localize to target promoters and act in a similar, rather than antagonistic, manner to regulate gene expression. In a follow-up study, I have used a novel method known as Global Run-on Sequencing (GRO-seq) to define the role of PARP-1 on the estrogen-regulated transcriptome at the level of the nascent transcript, rather than steady-state mRNA levels. I have produced libraries from MCF-7 cells treated with vehicle or 17[beta]estradiol (E2) under three conditions: (i) a control knockdown; (ii) a control knockdown plus a PARP inhibitor, PJ34; and (iii) a PARP-1 knockdown. I have determined that the estrogen response is highly maintained under PARP-1 knockdown or inhibition. Accordingly, upon estrogen treatment, PARP-1 localization patterns are largely unaffected. However, deeper analyses reveal a small number of genes where PARP-1 knockdown or inhibition reduces the estrogen response at the transcription level (GRO-seq) and at the steady state mRNA level (RT-qPCR). The NAD+ metabolite generated from the PARP-1/PARG reaction, ADPribose (ADPR), is a small molecule ligand that is used by macro domain-containing proteins. The histone variant macroH2A1 is one such protein that has generally been studied with respect to its role in transcriptional repression on the inactive X chromosome. However, recent studies have begun to explore a role for macroH2A1 in autosomal gene regulation, as a transcriptional repressor and a transcriptional activator. Recent results from the Kraus lab have shown that the transcriptional coactivator Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) interacts with the macro domain of macroH2A1 in a ligand-independent manner and shows a similar… Advisors/Committee Members: Kraus, William Lee (chair), Collins, Ruth N. (committee member), Lis, John T (committee member).

Subjects/Keywords: parp-1; gene regulation; estrogen signaling

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

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

APA (6th Edition):

Frizzell, K. (2011). Mechanisms Of Transcriptional Regulation By Proteins In The Nad+ Metabolic Pathway. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/33561

Chicago Manual of Style (16th Edition):

Frizzell, Kristine. “Mechanisms Of Transcriptional Regulation By Proteins In The Nad+ Metabolic Pathway.” 2011. Doctoral Dissertation, Cornell University. Accessed January 19, 2021. http://hdl.handle.net/1813/33561.

MLA Handbook (7th Edition):

Frizzell, Kristine. “Mechanisms Of Transcriptional Regulation By Proteins In The Nad+ Metabolic Pathway.” 2011. Web. 19 Jan 2021.

Vancouver:

Frizzell K. Mechanisms Of Transcriptional Regulation By Proteins In The Nad+ Metabolic Pathway. [Internet] [Doctoral dissertation]. Cornell University; 2011. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/1813/33561.

Council of Science Editors:

Frizzell K. Mechanisms Of Transcriptional Regulation By Proteins In The Nad+ Metabolic Pathway. [Doctoral Dissertation]. Cornell University; 2011. Available from: http://hdl.handle.net/1813/33561

.