The mammalian Sin3 proteins are required for muscle development and sarcomere specification

Chris Van Oevelen, Christopher Bowman, Jessica Pellegrino, Patrik Asp, Jemmie Cheng, Fabio Parisi, Mariann Micsinai, Yuval Kluger, Alphonse Chu, Alexandre Blais, Gregory David, Brian D. Dynlacht

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

The highly related mammalian Sin3A and Sin3B proteins provide a versatile platform for chromatinmodifying activities. Sin3-containing complexes play a role in gene repression through deacetylation of nucleosomes. Here, we explore a role for Sin3 in myogenesis by examining the phenotypes resulting from acute somatic deletion of both isoforms in vivo and from primary myotubes in vitro. Myotubes ablated for Sin3A alone, but not Sin3B, displayed gross defects in sarcomere structure that were considerably enhanced upon simultaneous ablation of both isoforms. Massively parallel sequencing of Sin3A- and Sin3B-bound genomic loci revealed a subset of target genes directly involved in sarcomere function that are positively regulated by Sin3A and Sin3B proteins. Both proteins were coordinately recruited to a substantial number of genes. Interestingly, depletion of Sin3B led to compensatory increases in Sin3A recruitment at certain target loci, but Sin3B was never found to compensate for Sin3A loss. Thus, our analyses describe a novel transcriptional role for Sin3A and Sin3B proteins associated with maintenance of differentiated muscle cells.

Original languageEnglish (US)
Pages (from-to)5686-5697
Number of pages12
JournalMolecular and cellular biology
Volume30
Issue number24
DOIs
StatePublished - Feb 15 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Van Oevelen, C., Bowman, C., Pellegrino, J., Asp, P., Cheng, J., Parisi, F., Micsinai, M., Kluger, Y., Chu, A., Blais, A., David, G., & Dynlacht, B. D. (2010). The mammalian Sin3 proteins are required for muscle development and sarcomere specification. Molecular and cellular biology, 30(24), 5686-5697. https://doi.org/10.1128/MCB.00975-10