Cucinotta, Christine E.
(2017)
Roles of the Nucleosome Acidic Patch in Regulating Histone Modifications and Transcription.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Proper transcription elongation is critical for all eukaryotes. One regulatory mechanism cells employ is modification of nucleosomes during transcription. H2B K123 monoubiquitylation (H2Bub) is a key histone posttranslational modification that correlates with transcription elongation, promotes downstream histone marks, and regulates chromatin architecture. The E2 and E3 enzymes, Rad6 and Bre1, catalyze H2Bub in collaboration with the Paf1 complex member Rtf1. Additionally, H2Bub and the histone chaperone complex FACT appear to be interdependent. While it is known that these factors promote and catalyze the modification, how these proteins interface with the nucleosome to promote transcription is still unclear. However, reports show that the nucleosome acidic patch is an important regulatory region that binds many different factors. This dissertation describes roles for the nucleosome acidic patch regulates the H2Bub modification cascade and transcription elongation efficiency in Saccharomyces cerevisiae. As the acidic patch is a hub for chromatin-binding proteins, I hypothesize that transcription elongation factors interface with the acidic patch to properly regulate gene expression. To determine whether the acidic patch may function directly in promoting H2Bub, I measured H2Bub levels in a minimal in vitro assay, and found that the acidic patch is required for proper H2Bub. To identify factors that bind to the nucleosome acidic patch in vivo, I implemented a proteomics approach that utilized site-specific crosslinking with which I uncovered an interaction between transcription elongation factors and the nucleosome acidic patch. These data, and that of others, show that the acidic patch can dynamically interact with chromatin-binding proteins to control gene expression.
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| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
23 September 2017 |
| Date Type: |
Publication |
| Defense Date: |
12 July 2017 |
| Approval Date: |
23 September 2017 |
| Submission Date: |
2 August 2017 |
| Access Restriction: |
5 year -- Restrict access to University of Pittsburgh for a period of 5 years. |
| Number of Pages: |
215 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Biological Sciences |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
chromatin, transcription, histone modifications, gene expression |
| Date Deposited: |
24 Sep 2017 00:07 |
| Last Modified: |
23 Sep 2022 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/32954 |
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