Chromatin remodeling (changing chromatin structure) is mediated by enzymes in eukaryotic cells. While several remodeling enzymes have been identified, little is known about how remodeling enzymes regulate gene expression in higher eukaryotes. It is also not known which enzymes regulate which genes, whether they work together, or why there are so many remodeling enzymes in higher eukaryotes. ? ? We investigate the role of chromatin remodeling in T cell activation. The experiments proposed use multiple approaches to continue our analysis of energy-dependent remodeling enzymes in higher eukaryotes. We are systematically asking what genes are regulated by which remodeling enzymes. We are using this information to ask what mechanism is used to regulate these target genes. We are also asking what the physiological roles of chromatin remodeling are in living cells. We focus on the remodeling protein hSNF2L, and compare it to the closely related protein hSNF2H and the more distantly related protein BRG1. We use T cell activation as a model system in our experiments, because the transcriptional program is relatively well understood, and also because several T cell genes are known to change chromatin structure during activation-induced gene regulation ? ? This program will provide important new information about the mechanism of energy-dependent remodeling enzymes. We will gain new insight into the link between remodeling and transcriptional regulation of mammalian genes. We will also learn about T cell activation, a central process in the immune system controlling lymphocyte development, differentiation and function.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM061011-02
Application #
6603461
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Carter, Anthony D
Project Start
2002-08-01
Project End
2007-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
2
Fiscal Year
2003
Total Cost
$284,185
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Ishii, Haruhiko; Du, Hansen; Zhang, Zhaoqing et al. (2009) Mi2beta shows chromatin enzyme specificity by erasing a DNase I-hypersensitive site established by ACF. J Biol Chem 284:7533-41
Lu, Jun; Pazin, Michael J; Ravid, Katya (2004) Properties of ets-1 binding to chromatin and its effect on platelet factor 4 gene expression. Mol Cell Biol 24:428-41
Ishii, Haruhiko; Sen, Ranjan; Pazin, Michael J (2004) Combinatorial control of DNase I-hypersensitive site formation and erasure by immunoglobulin heavy chain enhancer-binding proteins. J Biol Chem 279:7331-8