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DETERMINATION OF THE CAUSAL POTENTIAL OF HISTONE MODIFICATIONS
ON TRANSCRIPTION AND CHROMATIN STRUCTURE
by
Yuchen Si
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(BIOCHEMISTRY AND MOLECULAR BIOLOGY)
August 2012
Copyright 2012 Yuchen Si
Object Description
| Title | Determinination of the causal potential of histone modifications on transcription and chromatin structure |
| Author | Si, Yuchen |
| Author email | yuchensi@usc.edu;siyuchen1218@gmail.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Biochemistry and Molecular Biology |
| School | Keck School of Medicine |
| Date defended/completed | 2012-05-10 |
| Date submitted | 2012-07-25 |
| Date approved | 2012-07-25 |
| Restricted until | 2012-07-25 |
| Date published | 2012-07-25 |
| Advisor (committee chair) | Laird, Peter W. |
| Advisor (committee member) |
Laird-Offringa, Ite A. Tokes, Zoltan |
| Abstract | Histone modification is a major epigenetic regulatory mechanism that controls chromatin structure and gene expression potential. However, the causal potential of individual histone modifications remains largely unknown. Here, we report that G9a is able to initiate transcriptional repression when targeted to a robust mammalian promoter, the human EF1α promoter, in a transient reporter assay, while other histone methyltransferases, Suv39h1, Suv39h2, and PR-set7 fail to do so. We observed the same G9a-specific transcriptional repression from the human ubiquitin C promoter, suggesting that the G9a-initiated transcriptional repression might not be a promoter-dependent phenomenon. We found that the G9a catalytic SET domain is both necessary and sufficient to initiate repression. In addition, we found that the G9a SET domain is able to confer a repressive capability to a non-repressive histone methyltransferase, Suv39h1, when replacing the SET domain of Suv39h1. Further, a null mutation (H1166K) in the G9a SET domain completely abolished the repressive function, suggesting H3K9 di- methylation is mediating the repression. Our results provide evidence for a causal repressive function for H3K9 di-methylation and for the existence of potential functional differences among the histone methylations that have been uniformly considered as repressive mark. |
| Keyword | histone modification; G9a; Suv39h1; Suv39h2; Pr-set7; transcription; chromatin structure |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Contributing entity | University of Southern California |
| Rights | Si, Yuchen |
| Access conditions | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@usc.edu |
| Archival file | uscthesesreloadpub_Volume4/etd-SiYuchen-985.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Full text | DETERMINATION OF THE CAUSAL POTENTIAL OF HISTONE MODIFICATIONS ON TRANSCRIPTION AND CHROMATIN STRUCTURE by Yuchen Si A Thesis Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (BIOCHEMISTRY AND MOLECULAR BIOLOGY) August 2012 Copyright 2012 Yuchen Si |
