DOI

10.17077/etd.57vs-1bvo

Document Type

Dissertation

Date of Degree

Spring 2019

Access Restrictions

Access restricted until 07/29/2021

Degree Name

PhD (Doctor of Philosophy)

Degree In

Biochemistry

First Advisor

Musselman, Catherine A.

Second Advisor

Wallrath, Lori L.

First Committee Member

Spies, Maria

Second Committee Member

Fuentes, Ernesto

Third Committee Member

Geyer, Pamela

Fourth Committee Member

Manak, John

Abstract

Histone post-translational modifications (PTMs) are key determinants of the local chromatin landscape and critical for regulation of eukaryotic gene expression. These histone marks are deposited by a vast number of chromatin modifying enzymes and preferentially recognized by specific associated histone reader domains. Recognition of histone PTMs by histone reader domains is important for either targeting these complexes to chromatin or regulating their enzymatic activity once there. The Polycomb repressive complex 1 and 2 (PRC1 and PRC2) are two such chromatin modifying complexes that are critical for developmental gene repression. The enzymatic activity of PRC2 is tightly regulated by many histone reader domains whereas the PRC1 complex is targeted to chromatin through these domains. In this thesis, I explore how PRC1 and PRC2 functions are regulated by histone reader domains. I identify a previously unrecognized histone reader domain within the PRC2 complex, the EZH2 SANT1 domain, which has important implications for regulating PRC2 enzymatic activity. In addition, I explore the mechanism through which the CBX8 chromodomain targets the PRC1 complex to chromatin. Together, these studies provide significant insight into the regulation of chromatin modifying complexes by histone reader domains and how this occurs via multiple mechanisms.

Keywords

Chromatin, Histone Reader Domain, NMR, Nucleosome

Pages

xi, 166 pages

Bibliography

Includes bibliographical references (pages 156-166).

Comments

This thesis has been optimized for improved web viewing. If you require the original version, contact the University Archives at the University of Iowa: https://www.lib.uiowa.edu/sc/contact/.

Copyright

Copyright © 2019 Tyler M. Weaver

Available for download on Thursday, July 29, 2021

Included in

Biochemistry Commons

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