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

Sonia V. Forcales; Sonia Albini; Lorenzo Giordani; Barbora Malecova; Luca Cignolo; Andrei Chernov; Paula Coutinho; Valentina Saccone; Silvia Consalvi; Roy Williams; Kepeng Wang; Zhenguo Wu; Svetlana Baranovskaya; Andrew Miller; F. Jeffrey Dilworth; Pier Lorenzo Puri

doi:10.1038/emboj.2011.391

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

Sonia V. Forcales, Sonia Albini, Lorenzo Giordani, Barbora Malecova, Luca Cignolo, Andrei Chernov, Paula Coutinho, Valentina Saccone, Silvia Consalvi, Roy Williams, Kepeng Wang, Zhenguo Wu, Svetlana Baranovskaya, Andrew Miller, F. Jeffrey Dilworth, Pier Lorenzo Puri

Fondazione Santa Lucia

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	301-316
Number of pages	16
Journal	EMBO Journal
Volume	31
Issue number	2
DOIs	https://doi.org/10.1038/emboj.2011.391
Publication status	Published - Jan 18 2012

Keywords

chromatin
gene expression
muscle differentiation
myod
p38

ASJC Scopus subject areas

Molecular Biology
Biochemistry, Genetics and Molecular Biology(all)
Immunology and Microbiology(all)
Neuroscience(all)

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10.1038/emboj.2011.391

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Forcales, S. V., Albini, S., Giordani, L., Malecova, B., Cignolo, L., Chernov, A., Coutinho, P., Saccone, V., Consalvi, S., Williams, R., Wang, K., Wu, Z., Baranovskaya, S., Miller, A., Dilworth, F. J., & Puri, P. L. (2012). Signal-dependent incorporation of MyoD-BAF60c into Brg1-based SWI/SNF chromatin-remodelling complex. EMBO Journal, 31(2), 301-316. https://doi.org/10.1038/emboj.2011.391

Forcales, SV, Albini, S, Giordani, L, Malecova, B, Cignolo, L, Chernov, A, Coutinho, P, Saccone, V, Consalvi, S, Williams, R, Wang, K, Wu, Z, Baranovskaya, S, Miller, A, Dilworth, FJ & Puri, PL 2012, 'Signal-dependent incorporation of MyoD-BAF60c into Brg1-based SWI/SNF chromatin-remodelling complex', EMBO Journal, vol. 31, no. 2, pp. 301-316. https://doi.org/10.1038/emboj.2011.391

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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.",

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AU - Forcales, Sonia V.

AU - Albini, Sonia

AU - Giordani, Lorenzo

AU - Malecova, Barbora

AU - Cignolo, Luca

AU - Chernov, Andrei

AU - Coutinho, Paula

AU - Saccone, Valentina

AU - Consalvi, Silvia

AU - Williams, Roy

AU - Wang, Kepeng

AU - Wu, Zhenguo

AU - Baranovskaya, Svetlana

AU - Miller, Andrew

AU - Dilworth, F. Jeffrey

AU - Puri, Pier Lorenzo

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N2 - 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.

AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

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