The HDAC-Associated Sin3B Protein Represses DREAM Complex Targets and Cooperates with APC/C to Promote Quiescence

Cell Rep. 2018 Dec 4;25(10):2797-2807.e8. doi: 10.1016/j.celrep.2018.11.024.

Abstract

The mammalian DREAM complex is responsible for the transcriptional repression of hundreds of cell-cycle-related genes in quiescence. How the DREAM complex recruits chromatin-modifying entities to aid in its repression remains unknown. Using unbiased proteomics analysis, we have uncovered a robust association between the chromatin-associated Sin3B protein and the DREAM complex. We have determined that genetic inactivation of Sin3B results in the de-repression of DREAM target genes during quiescence but is insufficient to allow quiescent cells to resume proliferation. However, inactivation of APC/CCDH1 was sufficient for Sin3B-/- cells, but not parental cells, to re-enter the cell cycle. These studies identify Sin3B as a transcriptional corepressor associated with the DREAM complex in quiescence and reveals a functional cooperation between E2F target repression and APC/CCDH1 in the negative regulation of cell-cycle progression.

Keywords: DREAM; E2F; Sin3; cell cycle; quiescence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome / metabolism*
  • Cell Cycle*
  • Histone Deacetylases / metabolism*
  • Humans
  • Multiprotein Complexes / metabolism*
  • Protein Binding
  • Repressor Proteins / metabolism*
  • Transcription, Genetic

Substances

  • Multiprotein Complexes
  • Repressor Proteins
  • SIN3B protein, human
  • Anaphase-Promoting Complex-Cyclosome
  • Histone Deacetylases