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J. Biol. Chem., Vol. 281, Issue 51, 38974-38980, December 22, 2006
BRG1 Chromatin Remodeling Activity Is Required for Efficient Chromatin Binding by Repressor Element 1-silencing Transcription Factor (REST) and Facilitates REST-mediated Repression* 1![]() ![]() ![]() 2
From the
Chromatin remodeling enzymes such as SWI/SNF use the hydrolysis of ATP to power the movement of nucleosomes with respect to DNA. BRG1, one of the ATPases of the SWI/SNF complex, can be recruited by both activators and repressors, although the precise role of BRG1 in mechanisms of repression has thus far remained unclear. One transcription factor that recruits BRG1 as a corepressor is the repressor element 1-silencing transcription factor (REST). Here we address for the first time the mechanism of BRG1 activity in gene repression. We found that BRG1 enhanced REST-mediated repression at some REST target genes by increasing the interaction of REST with the local chromatin at its binding sites. Furthermore, REST-chromatin interactions, mediated by BRG1, were enhanced following an increase in histone acetylation in a manner dependent on the BRG1 bromodomain. Our data suggest that BRG1 facilitates REST repression by increasing the interaction between REST and chromatin. Such a mechanism may be applicable to other transcriptional repressors that utilize BRG1.
Received for publication, June 5, 2006 , and in revised form, September 26, 2006. * This work was supported by the Wellcome Trust. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 2 Current address: Centre for the Cellular Basis of Behaviour, King's College London, Inst. of Psychiatry, De Crespigny Park, Box PO37, Denmark Hill, London SE5 8AF, United Kingdom. 1 Supported by a Wellcome Trust Prize Ph.D. studentship. To whom correspondence should be addressed: Inst. of Membrane and Systems Biology, Garstang Bldg., University of Leeds, Mount Preston St., Leeds, LS2 9JT, United Kingdom. Tel.: 44-113-3437921; Fax: 44-113-3434228; E-mail: L.Ooi{at}leeds.ac.uk.
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