Dynamic BRG1 recruitment during T helper differentiation and activation reveals distal regulatory elements.
T helper cell differentiation and activation require specific transcriptional programs accompanied by changes in chromatin structure. However, little is known about the chromatin remodeling enzymes responsible. We performed genome-wide analysis to determine the general principles of BRG1 binding, followed by analysis of specific genes to determine whether these general rules were typical of key T cell genes. We found that binding of the remodeling protein BRG1 was programmed by both lineage and activation signals. BRG1 binding positively correlated with gene activity at protein-coding and microRNA (miRNA) genes. BRG1 binding was found at promoters and distal regions, including both novel and previously validated distal regulatory elements. Distal BRG1 binding correlated with expression, and novel distal sites in the Gata3 locus possessed enhancer-like activity, suggesting a general role for BRG1 in long-distance gene regulation. BRG1 recruitment to distal sites in Gata3 was impaired in cells lacking STAT6, a transcription factor that regulates lineage-specific genes. Together, these findings suggest that BRG1 interprets both differentiation and activation signals and plays a causal role in gene regulation, chromatin structure, and cell fate. Our findings suggest that BRG1 binding is a useful marker for identifying active cis-regulatory regions in protein-coding and miRNA genes.
Research Resources Branch, National Institute on Aging, NIH, Baltimore, Maryland 21224, USA.
Supriyo
S
De
Andrea L
AL
Wurster
Patricia
P
Precht
William H
WH
Wood
Kevin G
KG
Becker
Michael J
MJ
Pazin
D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D004265:DNA Helicases / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D050990:GATA3 Transcription Factor / Q000235:genetics; D006657:Histones / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology; D016131:Lymphocyte Subsets / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050791:STAT Transcription Factors / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism*; D024363:Transcription Initiation Site
D002843:Chromatin; D050990:GATA3 Transcription Factor; D006657:Histones; D035683:MicroRNAs; D009687:Nuclear Proteins; D050791:STAT Transcription Factors; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases; D008239:Lysine
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