A Role for Mammalian Sin3 in Permanent Gene Silencing

Chris van Oevelen, Jinhua Wang, Patrik Asp, Qin Yan, William G. Kaelin, Yuval Kluger, Brian David Dynlacht

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)359-370
Number of pages12
JournalMolecular Cell
Volume32
Issue number3
DOIs
StatePublished - Nov 7 2008

Bibliographical note

Funding Information:
We are grateful to members of the Dynlacht lab and to G. David for comments on the manuscript and helpful suggestions during the course of this study. We thank A. Bhattacharjee and G. Das for assistance with experiments. This work was supported by National Institutes of Health (NIH) grant CA077245 (to B.D.D.), NIH grant CA076120 (to W.G.K.), Susan Komen Postdoctoral Fellowship (to C.v.O.), and Department of Defense Breast Cancer Research Program Concept Award W81XWH-07-1-0581 (to Q.Y.). W.G.K. is an Investigator of the Howard Hughes Medical Institute.

Keywords

  • CELLCYCLE
  • DEVBIO
  • DNA

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