Dissertation/Thesis Abstract

Determination of the causal potential of histone modifications on transcription and chromatin structure
by Si, Yuchen, M.S., University of Southern California, 2012, 50; 1529054
Abstract (Summary)

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 EF1&agr; 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.

Indexing (document details)
Advisor: Laird, Peter
Commitee: Laird-Offringa, Ite, Tokes, Zoltan
School: University of Southern California
Department: Biochemistry and Molecular Biology
School Location: United States -- California
Source: MAI 51/03M(E), Masters Abstracts International
Subjects: Molecular biology
Publication Number: 1529054
ISBN: 978-1-267-69968-8
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