The goal of this application is to gain insight into the molecular mechanisms that govern cyclic AMP (cAMP)-mediated gene expression through the phosphorylation-dependent transcription factor, cyclic AMP response element binding-protein (CREB). Specifically, I will be focusing on the role that histone deactylase complexes (HDAC) play in regulating CREB-mediated transcription. My hypothesis is that the association of HDAC complexes with CREB block cellular gene expression by disrupting local chromatin structure and preventing phosphorylation of CREB by PKA in cells exposed to cAMP agonist. To test this hypothesis, I will identify components of the HDAC complexes that interact with CREB. To test whether endogenous HDAC complexes attenuates CREB-mediate transcription, I will also characterize mutant CREB polypeptides that are unable to associate with the HDAC complex. Finally, I will test whether HDAC-mediated deacetylation of promoter-bound nucleosomes hinders phosphorylation by blocking the association of PKA with chromatin.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM065740-02
Application #
6625783
Study Section
Special Emphasis Panel (ZRG1-F06 (20))
Program Officer
Tompkins, Laurie
Project Start
2002-09-16
Project End
2005-09-15
Budget Start
2003-09-16
Budget End
2004-09-15
Support Year
2
Fiscal Year
2003
Total Cost
$46,420
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037