title: Signal-dependent incorporation of MyoD-BAF60c into Brg1-based SWI/SNF chromatin-remodelling complex.
abstract: 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 p38α 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.
authors: Muscle Development and Regeneration Program, Sanford-Burnham Institute for Medical Research, La Jolla, CA, USA.
authors: Sonia V
authors: SV
authors: Forcales
authors: Sonia
authors: S
authors: Albini
authors: Lorenzo
authors: L
authors: Giordani
authors: Barbora
authors: B
authors: Malecova
authors: Luca
authors: L
authors: Cignolo
authors: Andrei
authors: A
authors: Chernov
authors: Paula
authors: P
authors: Coutinho
authors: Valentina
authors: V
authors: Saccone
authors: Silvia
authors: S
authors: Consalvi
authors: Roy
authors: R
authors: Williams
authors: Kepeng
authors: K
authors: Wang
authors: Zhenguo
authors: Z
authors: Wu
authors: Svetlana
authors: S
authors: Baranovskaya
authors: Andrew
authors: A
authors: Miller
authors: F Jeffrey
authors: FJ
authors: Dilworth
authors: Pier Lorenzo
authors: PL
authors: Puri
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004265:DNA Helicases / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D046912:Multiprotein Complexes; D024510:Muscle Development / Q000502:physiology*; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017570:MyoD Protein / Q000502:physiology*; D032446:Myoblasts / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology; D010766:Phosphorylation; D010769:Phosphothreonine / Q000032:analysis; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D046912:Multiprotein Complexes; D009124:Muscle Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C491649:SMARCD3 protein, human; C445179:SWI-SNF-B chromatin-remodeling complex; C494055:Smarcd3 protein, mouse; D014157:Transcription Factors; D010769:Phosphothreonine; D048051:p38 Mitogen-Activated Protein Kinases; C084108:SMARCA4 protein, human; C513194:Smarca4 protein, mouse; D004265:DNA Helicases