Journal Article

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

Pisano, David G, Cuadrado, Ana, Gómez‐López, Gonzalo, Remeseiro, Silvia, Losada, Ana

2012

Overview

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. Loss of the cohesin subunit SA1 causes developmental defects and transcriptional deregulation resembling familial cohesin dysfunction disorders such as CdLS. SA1‐containing complexes are enriched at insulator and promoter regions, suggesting gene expression control specifically by SA1‐, not SA2‐cohesin.

• Publisher: Nature Publishing Group UK,John Wiley & Sons, Ltd,Springer Nature B.V,Nature Publishing Group
• Subject: Animals / CdLS / Cell Cycle Proteins - deficiency / Cell Cycle Proteins - genetics / Cell Cycle Proteins - metabolism / ChIP‐sequencing / Chromosomal Proteins, Non-Histone - deficiency / Chromosomal Proteins, Non-Histone - genetics / Chromosomal Proteins, Non-Histone - metabolism / Chromosomes / Cohesins / De Lange Syndrome - genetics / EMBO06 / EMBO09 / Embryo, Mammalian / Embryonic Development / Embryos / Etiology / Fibroblasts / Gene Expression Regulation / Genes / Mice / Mice, Knockout / Molecular biology / mouse model / Protein Subunits - deficiency / Protein Subunits - genetics / Protein Subunits - metabolism / Proto-Oncogene Proteins c-myc - genetics / transcription / Vertebrates