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.
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