A novel role for the Aurora B kinase in epigenetic marking of silent chromatin in differentiated postmitotic cells

EMBO J. 2007 Nov 14;26(22):4657-69. doi: 10.1038/sj.emboj.7601875. Epub 2007 Oct 18.

Abstract

Combinatorial modifications of the core histones have the potential to fine-tune the epigenetic regulation of chromatin states. The Aurora B kinase is responsible for generating the double histone H3 modification tri-methylated K9/phosphorylated S10 (H3K9me3/S10ph), which has been implicated in chromosome condensation during mitosis. In this study, we have identified a novel role for Aurora B in epigenetic marking of silent chromatin during cell differentiation. We find that phosphorylation of H3 S10 by Aurora B generates high levels of the double H3K9me3/S10ph modification in differentiated postmitotic cells and also results in delocalisation of HP1beta away from heterochromatin in terminally differentiated plasma cells. Microarray analysis of the H3K9me3/S10ph modification shows a striking increase in the modification across repressed genes during differentiation of mesenchymal stem cells. Our results provide evidence that the Aurora B kinase has a role in marking silent chromatin independently of the cell cycle and suggest that targeting of Aurora B-mediated phosphorylation of H3 S10 to repressed genes could be a mechanism for epigenetic silencing of gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinase B
  • Aurora Kinases
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Cell Differentiation
  • Cell Line
  • Cells, Cultured
  • Epigenesis, Genetic
  • Gene Silencing*
  • Heterochromatin / genetics*
  • Histones / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred Strains
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation
  • Plasma Cells / cytology
  • Plasma Cells / metabolism
  • Protein-Serine-Threonine Kinases / metabolism*
  • Spleen / cytology

Substances

  • Heterochromatin
  • Histones
  • Aurkb protein, mouse
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases