Loss-of-function studies in the mouse have shown that the MADS box transcription factor MEF2C and the basic helix-loop-helix transcription factor dHAND are required for normal cardiac morphogenesis. Members of the MEF2 family of transcription factors bind a conserved A/T rich DNA sequence associated with most cardiac muscle structural genes. The overall goal of this proposal is to understand the mechanism by which MEF2C directs cardiac specific gene expression.
The specific aims of this proposal are: 1.) To identify cardiac muscle specific cofactors for MEF2C; 2.) To determine whether MEF2C interacts directly with dHAND; 3.) To intercross MEF2C and dHAND mutant mice in order to test for genetic interactions between these cardiogenic regulators. MEF2C cofactors will be identified using two-hybrid protein interaction screens and expression library screening. The ability of MEF2C to activate transcription in collaboration with dHAND or other cofactors will be evaluated using cardiac specific gene regulatory regions. These studies should yield important insights into transcriptional control of cardiac morphogenesis.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HD008363-03
Application #
6181965
Study Section
Biological Sciences 2 (BIOL)
Program Officer
Javois, Lorette Claire
Project Start
2000-08-01
Project End
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
3
Fiscal Year
2000
Total Cost
$37,516
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Biochemistry
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390