Open AccessThe Mammalian Sin3 Proteins Are Required for Muscle Development and Sarcomere Specification
Author(s) -
Chris van Oevelen,
Christopher J. Bowman,
Jessica Pellegrino,
Patrik Asp,
Jing Cheng,
Fulvio Parisi,
Mariann Micsinai,
Yuval Kluger,
Alphonse Chu,
Alexandre Blais,
David Gourichon,
Brian David Dynlacht
Publication year - 2010
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00975-10
Subject(s) - myogenesis , sarcomere , biology , microbiology and biotechnology , gene isoform , gene , myocyte , genetics
The highly related mammalian Sin3A and Sin3B proteins provide a versatile platform for chromatin-modifying 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 isoformsin vivo and from primary myotubesin 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.