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Molecular and Cellular Biology, February 2008, p. 1413-1426, Vol. 28, No. 4
0270-7306/08/$08.00+0     doi:10.1128/MCB.01301-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The HSA Domain of BRG1 Mediates Critical Interactions Required for Glucocorticoid Receptor-Dependent Transcriptional Activation In Vivo{triangledown}

Kevin W. Trotter,1 Hua-Ying Fan,2,3,4 Melissa L. Ivey,1 Robert E. Kingston,2,3 and Trevor K. Archer1*

Laboratory of Molecular Carcinogenesis, NIEHS/NIH, Research Triangle Park, North Carolina 27709,1 Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114,2 Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115,3 Division of Basic Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 191114

Received 19 July 2007/ Returned for modification 11 October 2007/ Accepted 26 November 2007

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.

* Corresponding author. Mailing address: Laboratory of Molecular Carcinogenesis, NIEHS/NIH, Research Triangle Park, NC 27709. Phone: (919) 316-4565. Fax: (919) 316-4566. E-mail: archer1{at}niehs.nih.gov

{triangledown} Published ahead of print on 17 December 2007.

Molecular and Cellular Biology, February 2008, p. 1413-1426, Vol. 28, No. 4
0270-7306/08/$08.00+0     doi:10.1128/MCB.01301-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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