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"TRANSCRIPTIONAL REGULATION CODES DEFINED BY COMBINATORIAL GENOMIC BINDING OF POL II, H2A.Z, ANP32E AND CDK9"

by
Hyewon Shin
Molecular Biology, Genetics & Cancer Program
M.S. 2010, Yonsei University College of Medicine, South Korea
B.S. 2008, Catholic University of Korea, South Korea


Thesis Advisor: Maha Abdellatif, M.D. Ph.D.
Professor
Department of Cellular Biology and Molecular Medicine

Wednesday, March 22, 2017
1:00 P.M., MSB Room G609


Abstract

Gene regulation involving pause-release versus de novo recruitment of RNA polymerase II (pol II) and its coordination with the binding of Cdk9, H2A.z, and Anp32e to transcription start sites (TSS) and gene bodies (in-gene), has not been examined. In this study, we explore transcriptional regulation in the heart during a process of hypertrophy, which we predicted involves genome-wide transcriptional remodeling that includes inter-dependent changes in the binding of the above mentioned regulatory factors. The findings uniquely reveal at least nine distinct patterns of transcription that are distinguished on the basis of specific combinatorial increases or decreases in the binding of pol II, Cdk9, Anp32e, and H2A.z occupancy, at the TSS and in-gene. In addition, the results uncover that inducible v. housekeeping genes are differentially regulated by de novo recruitment vs. pause-release mechanisms, respectively, in which the former is associated with an increase in Cdk9 and Anp32e at both the TSS in-gene, while the latter involves recruitment of Cdk9 to the TSS only. Moreover, knockdown of Anp32e confirmed its role as a positive regulator of gene expression. In contrast, tissue-specific genes exhibit unprecedented opposing changes in pol II and Cdk9. Thus, from these results, transcriptional codes begin to emerge that are predictive of the transcriptional status of a gene.


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