Gene expression control by nuclear phosphoinositides and chromatin

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Abstract/Contents

Abstract
The physiological state of the genome is chromatin. Chromatin is a dynamic polymer composed of genomic DNA, histone proteins, and other factors. Dysregulation of chromatin homeostasis can lead to diverse human pathologies including cancer. This work focuses on chromatin-based mechanisms of gene regulation; more specifically the (1) targeting and (2) stabilization of gene-regulatory proteins on the chromatin template. In regard to chromatin targeting, not much is known about how gene-regulatory proteins selectively associate with their targets. Herein we detail the discovery of a new targeting factor, the nuclear phospholipid phosphatidylinositol-5-phosphate (PtdIns(5)P). PtdIns(5)P directly interacts with the tumor suppressor ING2 (inhibitor of growth family member 2) in the nucleus to coordinate gene expression of select ING2 targets. In regard to chromatin stabilization, lysine methylation is a principle mechanism for retaining chromatin-effector modules at discrete chromatin zones. Numerous lysine methylation events have been discovered on the major protein component of chromatin, histones, but relatively few specific modules have been characterized to sense these modifications. We screened through a library of putative methyl-lysine binding domains, which resulted in the identification of three novel chromatin binding modules. Taken together these data shed insight into the molecular modes of action of gene regulation by chromatin and phosphoinositide pathways.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2012
Issuance monographic
Language English

Creators/Contributors

Associated with Bua, Dennis Jacob
Associated with Stanford University, Department of Biology.
Primary advisor Gozani, Or Pinchas
Thesis advisor Gozani, Or Pinchas
Thesis advisor Morrison, Ashby J
Thesis advisor Nelson, W. J. (W. James)
Advisor Morrison, Ashby J
Advisor Nelson, W. J. (W. James)

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Dennis Jacob Bua.
Note Submitted to the Department of Biology.
Thesis Ph.D. Stanford University 2012
Location electronic resource

Access conditions

Copyright
© 2012 by Dennis Jacob Bua
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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