title: A unique role of cohesin-SA1 in gene regulation and development.
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.
authors.affiliation: Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Remeseiro
authors.forename: Ana
authors.initials: A
authors.lastname: Cuadrado
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Gómez-López
authors.forename: David G
authors.initials: DG
authors.lastname: Pisano
authors.forename: Ana
authors.initials: A
authors.lastname: Losada
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D003635:De Lange Syndrome / Q000235:genetics; D004622:Embryo, Mammalian; D047108:Embryonic Development; D005347:Fibroblasts; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D021122:Protein Subunits / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D021122:Protein Subunits; D016271:Proto-Oncogene Proteins c-myc; D000097722:Cohesins; C489428:Myc protein, mouse