A unique role of cohesin-SA1 in gene regulation and development.
EMBO J, 2012/5/02;31(9):2090-102.
Remeseiro S[1], Cuadrado A, Gómez-López G, Pisano DG, Losada A
Affiliations
PMID: 22415368DOI: 10.1038/emboj.2012.60
Impact factor: 14.012
Abstract
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.
MeSH terms
Animals; Cell Cycle Proteins; Chromosomal Proteins, Non-Histone; De Lange Syndrome; Embryo, Mammalian; Embryonic Development; Fibroblasts; Gene Expression Regulation; Mice; Mice, Knockout; Protein Subunits; Proto-Oncogene Proteins c-myc; Cohesins
More resources
Full text:
Europe PubMed Central; PubMed Central
EndNote: Download