A unique role of cohesin-SA1 in gene regulation and development

EMBO J. 2012 May 2;31(9):2090-102. doi: 10.1038/emboj.2012.60. Epub 2012 Mar 13.


Vertebrates have two cohesin complexes that consist of Smc1, Smc3, Rad21/Scc1 and either SA1 or SA2, but their functional specificity is unclear. Mouse embryos lacking SA1 show developmental delay and die before birth. Comparison of the genome-wide distribution of cohesin in wild-type and SA1-null cells reveals that SA1 is largely responsible for cohesin accumulation at promoters and at sites bound by the insulator protein CTCF. As a consequence, ablation of SA1 alters transcription of genes involved in biological processes related to Cornelia de Lange syndrome (CdLS), a genetic disorder linked to dysfunction of cohesin. We show that the presence of cohesin-SA1 at the promoter of myc and of protocadherin genes positively regulates their expression, a task that cannot be assumed by cohesin-SA2. Lack of SA1 also alters cohesin-binding pattern along some gene clusters and leads to dysregulation of genes within. We hypothesize that impaired cohesin-SA1 function in gene expression underlies the molecular aetiology of CdLS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / deficiency
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromosomal Proteins, Non-Histone / deficiency
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • De Lange Syndrome / genetics
  • Embryo, Mammalian
  • Embryonic Development*
  • Fibroblasts
  • Gene Expression Regulation*
  • Mice
  • Mice, Knockout
  • Protein Subunits / deficiency
  • Protein Subunits / genetics
  • Protein Subunits / metabolism*
  • Proto-Oncogene Proteins c-myc / genetics


  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Myc protein, mouse
  • Protein Subunits
  • Proto-Oncogene Proteins c-myc
  • cohesins