The HSA domain of BRG1 mediates critical interactions required for glucocorticoid receptor-dependent transcriptional activation in vivo.
The packaging of eukaryotic DNA into chromatin can create an impediment to transcription by hindering binding of essential factors required for transcription. The mammalian SWI/SNF remodeling complex has been shown to alter local chromatin structure and facilitate recruitment of transcription factors. BRG1 (or hBrm), the central ATPase of the human SWI/SNF complex, is a critical factor for the functional activity of nuclear receptor complexes. Analysis using BRG1/SNF2h chimeras suggests BRG1 may contain previously uncharacterized functional motifs important for SWI/SNF. To identify these regions, BRG1 truncation and deletion mutants were designed, characterized, and utilized in a series of assays to evaluate transcriptional activation and chromatin remodeling by the glucocorticoid receptor. We identified a domain within the N terminus of BRG1 that mediates critical protein interactions within SWI/SNF. We find the HSA domain of BRG1 is required to mediate the interaction with BAF250a/ARID1A and show this association is necessary for transcriptional activation from chromatin mouse mammary tumor virus or endogenous promoters in vivo. These studies suggest BAF250a is a necessary facilitator of BRG1-mediated chromatin remodeling required for SWI/SNF-dependent transcriptional activation.
Trotter
Kevin W
KW
Laboratory of Molecular Carcinogenesis, NIEHS/NIH, Research Triangle Park, NC 27709, USA.
Fan
Hua-Ying
HY
Ivey
Melissa L
ML
Kingston
Robert E
RE
Archer
Trevor K
TK
D000818:Animals; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004265:DNA Helicases / Q000737:chemistry* / Q000378:metabolism*; D004268:DNA-Binding Proteins; D006801:Humans; D008324:Mammary Tumor Virus, Mouse; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D015533:Transcriptional Activation
C112476:ARID1A protein, human; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D050505:Mutant Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; D011965:Receptors, Glucocorticoid; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases