Cohesin acetyltransferase Esco2 is a cell viability factor and is required for cohesion in pericentric heterochromatin

EMBO J. 2012 Jan 4;31(1):71-82. doi: 10.1038/emboj.2011.381. Epub 2011 Nov 18.

Abstract

Sister chromatid cohesion, mediated by cohesin and regulated by Sororin, is essential for chromosome segregation. In mammalian cells, cohesion establishment and Sororin recruitment to chromatin-bound cohesin depends on the acetyltransferases Esco1 and Esco2. Mutations in Esco2 cause Roberts syndrome, a developmental disease in which mitotic chromosomes have a 'railroad' track morphology. Here, we show that Esco2 deficiency leads to termination of mouse development at pre- and post-implantation stages, indicating that Esco2 functions non-redundantly with Esco1. Esco2 is transiently expressed during S-phase when it localizes to pericentric heterochromatin (PCH). In interphase, Esco2 depletion leads to a reduction in cohesin acetylation and Sororin recruitment to chromatin. In early mitosis, Esco2 deficiency causes changes in the chromosomal localization of cohesin and its protector Sgo1. Our results suggest that Esco2 is needed for cohesin acetylation in PCH and that this modification is required for the proper distribution of cohesin on mitotic chromosomes and for centromeric cohesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / metabolism*
  • Animals
  • Cell Cycle Proteins / metabolism*
  • Cell Survival*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • HeLa Cells
  • Heterochromatin / metabolism*
  • Humans
  • Mice
  • S Phase
  • Transfection

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Heterochromatin
  • cohesins
  • Acetyltransferases
  • establishment of cohesion 1 homolog 2, mouse