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 journalArticle

80 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
Externally publishedYes

Keywords

  • CELLCYCLE
  • DEVBIO
  • DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'A Role for Mammalian Sin3 in Permanent Gene Silencing'. Together they form a unique fingerprint.

  • Cite this

    van Oevelen, C., Wang, J., Asp, P., Yan, Q., Kaelin, W. G., Kluger, Y., & Dynlacht, B. D. (2008). A Role for Mammalian Sin3 in Permanent Gene Silencing. Molecular Cell, 32(3), 359-370. https://doi.org/10.1016/j.molcel.2008.10.015