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A unique role of cohesin‐SA1 in gene regulation and development
Author(s) -
Remeseiro Silvia,
Cuadrado Ana,
GómezLópez Gonzalo,
Pisano David G,
Losada Ana
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.60
Subject(s) - biology , cohesin , genetics , gene , regulation of gene expression , computational biology , microbiology and biotechnology , meiosis
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.