期刊
EMBO JOURNAL
卷 31, 期 2, 页码 301-316出版社
WILEY
DOI: 10.1038/emboj.2011.391
关键词
chromatin; gene expression; muscle differentiation; myod; p38
资金
- National Institute of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [R01 AR056712, AR053779]
- Associazione Italiana Ricerca sul Cancro (AIRC)
- Sanford Children Health Research award
- European Community [FP7-Health-2009 ENDOSTEM 241440]
- CIRM
- Instituto de Salud Carlos III [PI09/2444]
- Fondazione Telethon Funding Source: Custom
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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