The mammalian Sin3 proteins are required for muscle development and sarcomere specification.
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 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.
Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
Chris
C
van Oevelen
Christopher
C
Bowman
Jessica
J
Pellegrino
Patrik
P
Asp
Jemmie
J
Cheng
Fabio
F
Parisi
Mariann
M
Micsinai
Yuval
Y
Kluger
Alphonse
A
Chu
Alexandre
A
Blais
Gregory
G
David
Brian D
BD
Dynlacht
D000818:Animals; D002460:Cell Line; D017353:Gene Deletion; D051379:Mice; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012518:Sarcomeres / Q000502:physiology* / Q000648:ultrastructure; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D015996:Survival Rate
D020033:Protein Isoforms; D012097:Repressor Proteins; C099683:SIN3A transcription factor; C115812:Sin3b protein, mouse; D056264:Sin3 Histone Deacetylase and Corepressor Complex