BRG1 chromatin remodeling activity is required for efficient chromatin binding by repressor element 1-silencing transcription factor (REST) and facilitates REST-mediated repression.
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.
Ooi
Lezanne
L
Institute of Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, United Kingdom. L.Ooi@leeds.ac.uk
Belyaev
Nikolai D
ND
Miyake
Katsuhide
K
Wood
Ian C
IC
Buckley
Noel J
NJ
D000107:Acetylation; D000255:Adenosine Triphosphate / Q000737:chemistry; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry*; D004265:DNA Helicases / Q000737:chemistry / Q000502:physiology*; D006657:Histones / Q000737:chemistry; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D012097:Repressor Proteins / Q000737:chemistry* / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry* / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D000099229:RE1-Silencing Transcription Factor
D000255:Adenosine Triphosphate; D002843:Chromatin; D004265:DNA Helicases; D006657:Histones; D006877:Hydroxamic Acids; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor; C012589:trichostatin A; C084108:SMARCA4 protein, human