Date of Award

Fall 2010

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Biology

First Advisor

Jonathan A. Epstein

Abstract

HDACs can modify the structure and function of chromatin to regulate gene expression and can also modify many non-histone proteins that regulate cell function and signaling. HDACs have attracted increasing interest because they are involved in a variety of physiologic and pathophysiologic processes including stem cell maintenance, differentiation, cancer, inflammation and cardiac diseases. In the absence of Hdac2, mice display myocyte hyper-proliferation during embryonic development and resistance to cardiac hypertrophy in adulthood. This doctoral dissertation examines the function of two Hdac2 downstream targets, Inpp5f and Gata4, in regulating adult cardiac hypertrophy and embryonic myocyte proliferation, respectively. My results suggest that Inpp5f is an important endogenous modulator of the cardiac response to stress. I also performed studies to show that, in the absence of Hdac2 in the embryonic heart, hyper-acetylated Gata4 is responsible for myocyte hyper-proliferation. These findings provide a framework for understanding the role of Hdac2 in embryonic heart development and adult cardiac diseases.

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