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

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...

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Veröffentlicht in:The EMBO journal 2012-01, Vol.31 (2), p.301-316
Hauptverfasser: Forcales, Sonia V, Albini, Sonia, Giordani, Lorenzo, Malecova, Barbora, Cignolo, Luca, Chernov, Andrei, Coutinho, Paula, Saccone, Valentina, Consalvi, Silvia, Williams, Roy, Wang, Kepeng, Wu, Zhenguo, Baranovskaya, Svetlana, Miller, Andrew, Dilworth, F Jeffrey, Puri, Pier Lorenzo
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container_end_page 316
container_issue 2
container_start_page 301
container_title The EMBO journal
container_volume 31
creator Forcales, Sonia V
Albini, Sonia
Giordani, Lorenzo
Malecova, Barbora
Cignolo, Luca
Chernov, Andrei
Coutinho, Paula
Saccone, Valentina
Consalvi, Silvia
Williams, Roy
Wang, Kepeng
Wu, Zhenguo
Baranovskaya, Svetlana
Miller, Andrew
Dilworth, F Jeffrey
Puri, Pier Lorenzo
description 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. The SWI/SNF chromatin‐remodelling complex regulates myogenic gene expression during muscle differentiation. BAF60c, a SWI/SNF subunit, recruits the muscle determinant transcription factor MyoD to target genes, facilitates chromatin remodelling and gene activation after phosphorylation by p38α MAP‐kinase.
doi_str_mv 10.1038/emboj.2011.391
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The SWI/SNF chromatin‐remodelling complex regulates myogenic gene expression during muscle differentiation. 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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. The SWI/SNF chromatin‐remodelling complex regulates myogenic gene expression during muscle differentiation. BAF60c, a SWI/SNF subunit, recruits the muscle determinant transcription factor MyoD to target genes, facilitates chromatin remodelling and gene activation after phosphorylation by p38α MAP‐kinase.</abstract><cop>Chichester, UK</cop><pub>John Wiley &amp; Sons, Ltd</pub><pmid>22068056</pmid><doi>10.1038/emboj.2011.391</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Cell Line
Cellular biology
Chromatin
Chromatin - genetics
Chromosomal Proteins, Non-Histone - antagonists & inhibitors
Chromosomal Proteins, Non-Histone - chemistry
Chromosomal Proteins, Non-Histone - genetics
Chromosomal Proteins, Non-Histone - physiology
DNA Helicases - physiology
EMBO09
EMBO37
Fibroblasts - metabolism
Gene expression
Gene Expression Regulation - genetics
HeLa Cells - metabolism
Humans
MAP Kinase Signaling System
Mice
Molecular biology
Multiprotein Complexes
Muscle Development - physiology
muscle differentiation
Muscle Proteins - antagonists & inhibitors
Muscle Proteins - chemistry
Muscle Proteins - genetics
Muscle Proteins - physiology
Myoblasts - metabolism
myod
MyoD Protein - physiology
Nuclear Proteins - physiology
p38
p38 Mitogen-Activated Protein Kinases - physiology
Phosphorylation
Phosphothreonine - analysis
Protein Processing, Post-Translational
RNA Interference
RNA, Small Interfering - pharmacology
Signal transduction
Transcription Factors - antagonists & inhibitors
Transcription Factors - chemistry
Transcription Factors - genetics
Transcription Factors - physiology
Two-Hybrid System Techniques
title Signal-dependent incorporation of MyoD-BAF60c into Brg1-based SWI/SNF chromatin-remodelling complex
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