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You searched for +publisher:"University of Iowa" +contributor:("Price, David H."). Showing records 1 – 2 of 2 total matches.

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University of Iowa

1. Nilson, Kyle Andrew. Regulation of Pol II transcription and mRNA capping.

Degree: PhD, Molecular and Cell Biology, 2016, University of Iowa

In humans, RNA polymerase II is the sole source of messenger RNAs that are ultimately translated into proteins and its transcriptional activity is highly regulated. Mechanisms have evolved to control which, when, and to what degree genes are transcribed. Because most cells have the same genome, control of transcription is essential in maintaining cellular identity. Misregulation of Pol II transcription is a hallmark of both cancer and retroviral infection. This research investigates the regulation of Pol II transcription and related co-transcriptional mRNA capping. Chromatin immunoprecipitation experiments were used to characterize the composition of nucleosomes and Pol II, DSIF and NELF occupancies at bidirectional promoters and enhancers. In collaboration with Alberto Bosque and Vicente Planelles, sequencing experiments were performed in a primary T cell model of HIV latency and a role for sequence-specific recruitment of STAT5 was established in HIV reactivation. In contrast, analysis of Myc binding in vitro and in cells demonstrated that transcription machinery played a major role in recruiting Myc to genomic sites. A precise method was also developed to detect polymerase-associated nascent transcripts in nuclei. The roles of Cdk7, a subunit of TFIIH that phosphorylates Pol II during initiation, were characterized by treatment of nuclear extracts and cells with THZ1, a recently developed covalent inhibitor with anti-cancer properties. Inhibition of Cdk7 was demonstrated to cause defects in Pol II phosphorylation, co-transcriptional capping, promoter proximal pausing, and productive elongation. Capping of nascent RNAs was found to be spatially and temporally regulated in part by a previously undescribed THZ1-sensitive factor present in nuclear extract. THZ1 impacted pausing through a capping-independent block of DSIF and NELF loading. The P-TEFb-dependent transition into productive elongation was also inhibited by THZ1, likely due to misloading of DSIF. In vitro and sequencing methods were used to describe an extremely rapid and global transcriptional response to hydrogen peroxide. During periods of oxidative stress, termination was likely inhibited and Pol II accumulated at promoters and enhancers after as few as two minutes, and clearance of these polymerases required P-TEFb. In the presence of flavopiridol, a potent P-TEFb inhibitor, non-productive elongation was observed and a potential role for P-TEFb in termination was proposed. Advisors/Committee Members: Price, David H. (supervisor).

Subjects/Keywords: ChIP-Seq; mRNA Capping; Pol II; P-TEFb; THZ1; Cell Biology

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APA (6th Edition):

Nilson, K. A. (2016). Regulation of Pol II transcription and mRNA capping. (Doctoral Dissertation). University of Iowa. Retrieved from https://ir.uiowa.edu/etd/5584

Chicago Manual of Style (16th Edition):

Nilson, Kyle Andrew. “Regulation of Pol II transcription and mRNA capping.” 2016. Doctoral Dissertation, University of Iowa. Accessed May 22, 2019. https://ir.uiowa.edu/etd/5584.

MLA Handbook (7th Edition):

Nilson, Kyle Andrew. “Regulation of Pol II transcription and mRNA capping.” 2016. Web. 22 May 2019.

Vancouver:

Nilson KA. Regulation of Pol II transcription and mRNA capping. [Internet] [Doctoral dissertation]. University of Iowa; 2016. [cited 2019 May 22]. Available from: https://ir.uiowa.edu/etd/5584.

Council of Science Editors:

Nilson KA. Regulation of Pol II transcription and mRNA capping. [Doctoral Dissertation]. University of Iowa; 2016. Available from: https://ir.uiowa.edu/etd/5584

2. Krueger, Brian. Regulated release of P-Tefb from the 7sk Snrnp.

Degree: PhD, Molecular and Cellular Biology, 2009, University of Iowa

Regulation of transcription elongation by P-TEFb is critical for proper gene expression and cell survival. The cell possesses large quantities of P-TEFb, but the vast majority of it is locked away and inactive in the 7SK snRNP. Since the discovery of the 7SK snRNP, research has been conducted to determine how P-TEFb is released from this complex. The goal of the research presented in this thesis is to better understand how the 7SK snRNP regulates P-TEFb and ultimately, gene expression. This work documents the discovery and characterization of the 7SK stability protein LARP7. LARP7 is is associated with 7SK regardless of the presence of P-TEFb and HEXIM1. Stabilization of 7SK is essential for maintenance of the RNP because loss of LARP7 results in an increase in free P-TEFb and a significant reduction in the amount of 7SK. These results indicate that stabilization of the 7SK snRNP by LARP7 is important for regulating P-TEFb homeostasis. Although P-TEFb was first characterized from Drosophila lysates, the conservation of the 7SK snRNP and the mechanisms regulating P-TEFb inhibition have not been described. Here, the Drosophila melanogaster homologues of LARP7 and 7SK are characterized. These studies show that the system of P-TEFb regulation is similar in flies and this makes Drosophila an attractive model system for studying P-TEFb regulation through embryonic and larval development. Finally, factors and modifications involved in releasing P-TEFb directly are explored. An assay was developed for discovering proteins that can bind to and release P-TEFb from the 7SK snRNP. Use of this assay showed that post-translational modification of the components of the 7SK snRNP do not cause P-TEFb release directly. However, HIV Tat and the C-terminal P-TEFb binding region of the bromodomain containing protein, Brd4, are capable of extracting P-TEFb directly. Most importantly, the release of P-TEFb is followed by a conformational change in 7SK RNA that prevents the continued binding of HEXIM1 to the complex. P-TEFb release from the 7SK snRNP is the result of direct extraction of P-TEFb by viral or cellular proteins, and not post-translational modifications or a competition between HEXIM1 and hnRNP proteins for 7SK binding. Advisors/Committee Members: Price, David H. (supervisor).

Subjects/Keywords: 7SK; 7SK snRNP; Conformational Change; Drosophila; LARP7; P-TEFb; Cell Biology

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

APA (6th Edition):

Krueger, B. (2009). Regulated release of P-Tefb from the 7sk Snrnp. (Doctoral Dissertation). University of Iowa. Retrieved from https://ir.uiowa.edu/etd/839

Chicago Manual of Style (16th Edition):

Krueger, Brian. “Regulated release of P-Tefb from the 7sk Snrnp.” 2009. Doctoral Dissertation, University of Iowa. Accessed May 22, 2019. https://ir.uiowa.edu/etd/839.

MLA Handbook (7th Edition):

Krueger, Brian. “Regulated release of P-Tefb from the 7sk Snrnp.” 2009. Web. 22 May 2019.

Vancouver:

Krueger B. Regulated release of P-Tefb from the 7sk Snrnp. [Internet] [Doctoral dissertation]. University of Iowa; 2009. [cited 2019 May 22]. Available from: https://ir.uiowa.edu/etd/839.

Council of Science Editors:

Krueger B. Regulated release of P-Tefb from the 7sk Snrnp. [Doctoral Dissertation]. University of Iowa; 2009. Available from: https://ir.uiowa.edu/etd/839

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