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Signal-dependent incorporation of MyoD-BAF60c into Brg1-based SWI/SNF chromatin-remodelling complex

  作者 Forcales, SV; Albini, S; Giordani, L; Malecova, B; Cignolo, L; Chernov, A; Coutinho, P; Saccone, V; Consalvi, S; Williams, R; Wang, KP; Wu, ZG; Baranovskaya, S; Miller, A; Dilworth, FJ; Puri, PL  
  选自 期刊  EMBO journal;  卷期  2012年31-2;  页码  301-316  
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[摘要]Tissue-specific transcriptional activators initiate differentiation towards specialized cell types by inducing chromatin modifications permissive for transcription at target loci, through the recruitment of SWItch/Sucrose NonFermentable (SWI/SNF) chromatin-remodelling complex. However, the molecular mechanism that regulates SWI/SNF nuclear distribution in response to differentiation signals is unknown. We show that the muscle determination factor MyoD and the SWI/SNF subunit BAF60c interact on the regulatory elements of MyoD-target genes in myoblasts, prior to activation of transcription. BAF60c facilitates MyoD binding to target genes and marks the chromatin for signal-dependent recruitment of the SWI/SNF core to muscle genes. BAF60c phosphorylation on a conserved threonine by differentiation-activated p38 alpha kinase is the signal that promotes incorporation of MyoD-BAF60c into a Brg1-based SWI/SNF complex, which remodels the chromatin and activates transcription of MyoD-target genes. Our data support an unprecedented two-step model by which pre-assembled BAF60c-MyoD complex directs recruitment of SWI/SNF to muscle loci in response to differentiation cues. The EMBO Journal (2012) 31, 301-316. doi:10.1038/emboj.2011.391; Published online 8 November 2011

 
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