Title: Analysis of the role of CHD1 in chromatin structure and transcription

PI:  Jennifer Armstrong

Funding Agency:  NSF

Division: Molecular and Cellular Biosciences

NSF Program: Genes and Genomes Systems

Amount: $ 303,878

Dates:  05/2007 – 04/2010

Abstract

Chromatin remodeling factors use the energy of ATP to modulate the structure of chromatin, thereby regulating processes such as transcription, replication, and repair.  While significant advances have been made in regards to the mechanism of action of these ATPases in vitro, much remains unknown regarding their activities in vivo.  The long-term goal of this research is to understand how the CHD1 chromatin remodeling and assembly factor is regulated and targeted in vivoDrosophila melanogaster is an ideal model system in which to study the actions of this unusual protein.  The goal of this project is to use the powerful tools of Drosophila genetics to investigate the in vivo activities of CHD1 (chromodomain, helicase, DNA-binding domain), an unusual ATPase that displays both nucleosome remodeling and assembly activities in vitro.  This project addresses the specific hypothesis that CHD1 functions globally to reassemble chromatin on active genes.  This hypothesis is being addressed by pursuing three specific aims (1) Investigate the in vivo function of CHD1 by examining phenotypes of both gain of function and loss of function chd1 mutants.  (2) Determine the relative contributions of each of the conserved protein domains.  (3) Examine the consequences of both gain and loss of CHD1 ATPase activity on chromosome structure and RNA Polymerase II.  This project employs a combination of genetic and cell biological approaches to analyze mutant phenotypes, chromosome morphology, and transcription.  These well-established techniques are amenable to undergraduate research, and have been extensively used by the PI in her studies of related chromatin remodeling factors.  The results of these experiments should provide significant insights into the function and regulation of CHD1, a highly conserved yet poorly understood ATPase. 

The goal of this research is to understand how changes in chromosome structure impact gene activity in a developing organism.  This project is focused on understanding the function of CHD1, a highly conserved protein that utilizes the energy of ATP to modify chromosome structure.  Undergraduate science students from Claremont McKenna, Scripps, and Pitzer Colleges are conducting this research in the interdisciplinary Keck Science Department (Biology, Chemistry, and Physics).  Scripps is an all-women's college, while Claremont McKenna and Pitzer are the 5th and 7th most ethnically diverse liberal arts colleges in the top tier.  This diverse student body allows the encouragement and recruitment of science students from historically underrepresented groups.