A role for mammalian Sin3 in permanent gene silencing.
The multisubunit Sin3 corepressor complex regulates gene transcription through deacetylation of nucleosomes. However, the full range of Sin3 activities and targets is not well understood. Here, we have investigated genome-wide binding of mouse Sin3 and RBP2 as well as histone modifications and nucleosome positioning as a function of myogenic differentiation. Remarkably, we find that Sin3 complexes spread immediately downstream of the transcription start site on repressed and transcribed genes during differentiation. We show that RBP2 is part of a Sin3 complex and that on a subset of E2F4 target genes, the coordinated activity of Sin3 and RBP2 leads to deacetylation, demethylation, and repositioning of nucleosomes. Our work provides evidence for coordinated binding of Sin3, chromatin modifications, and chromatin remodeling within discrete regulatory regions, suggesting a model in which spreading of Sin3 binding is ultimately linked to permanent gene silencing on a subset of E2F4 target genes.
van Oevelen
Chris
C
New York University School of Medicine, NYU Cancer Institute, 522 1st Avenue, New York, NY 10016, USA.
Wang
Jinhua
J
Asp
Patrik
P
Yan
Qin
Q
Kaelin
William G
WG
Kluger
Yuval
Y
Dynlacht
Brian David
BD
D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D004261:DNA Replication; D050704:E2F4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D032446:Myoblasts / Q000166:cytology / Q000502:physiology*; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D050704:E2F4 Transcription Factor; C493763:E2f4 protein, mouse; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex