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Publication : BRG1-mediated chromatin remodeling regulates differentiation and gene expression of T helper cells.

First Author  Wurster AL Year  2008
Journal  Mol Cell Biol Volume  28
Issue  24 Pages  7274-85
PubMed ID  18852284 Mgi Jnum  J:143289
Mgi Id  MGI:3826325 Doi  10.1128/MCB.00835-08
Citation  Wurster AL, et al. (2008) BRG1-mediated chromatin remodeling regulates differentiation and gene expression of T helper cells. Mol Cell Biol 28(24):7274-85
abstractText  During T helper cell differentiation, distinct programs of gene expression play a key role in defining the immune response to an environmental challenge. How chromatin remodeling events at the associated cytokine loci control differentiation is not known. We found that the ATP-dependent remodeling enzyme subunit BRG1 was required for T helper 2 (Th2) differentiation and Th2 cytokine transcription. BRG1 binding to cytokine genes was regulated by the extent of differentiation, the extent of activation, and cell fate. BRG1 was required for some features of the chromatin structure in target genes (DNase I hypersensitivity and histone acetylation), suggesting that BRG1 remodeling activity was directly responsible for changes in gene expression. NFAT and STAT6 activity were required for BRG1 recruitment to the Th2 locus control region, and STAT6 associated with BRG1 in a differentiation-inducible manner, suggesting direct recruitment of BRG1 to the bound loci. Together, these findings suggest BRG1 interprets differentiation signals and plays a causal role in gene regulation, chromatin structure, and cell fate.
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