Histone deacetylase 3 is required for centromeric H3K4 deacetylation and sister chromatid cohesion

Genes Dev. 2008 Oct 1;22(19):2639-44. doi: 10.1101/gad.484108.

Abstract

We describe here the role of histone deacetylase 3 (HDAC3) in sister chromatid cohesion and the deacetylation of histone H3 Lys 4 (H3K4) at the centromere. HDAC3 knockdown induced spindle assembly checkpoint activation and sister chromatid dissociation. The depletion of Polo-like kinase 1 (Plk1) or Aurora B restored cohesion in HDAC3-depleted cells. HDAC3 was also required for Shugoshin localization at centromeres. Finally, we show that HDAC3 depletion results in the acetylation of centromeric H3K4, correlated with a loss of dimethylation at the same position. These findings provide a functional link between sister chromatid cohesion and the mitotic "histone code".

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Aurora Kinase B
  • Aurora Kinases
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Centromere / metabolism*
  • HeLa Cells
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Histones / chemistry*
  • Histones / metabolism*
  • Humans
  • Lysine / chemistry
  • Mitosis
  • Phosphorylation
  • Polo-Like Kinase 1
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • RNA, Small Interfering / genetics
  • Sister Chromatid Exchange / physiology*
  • Transfection

Substances

  • Cell Cycle Proteins
  • Histone Deacetylase Inhibitors
  • Histones
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • SGO1 protein, human
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases
  • Histone Deacetylases
  • histone deacetylase 3
  • Lysine