A unique role of cohesin-SA1 in gene regulation and development.
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 c...
| Autores: | , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2012 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/17658 |
| Acceso en línea: | http://hdl.handle.net/20.500.12105/17658 |
| Access Level: | acceso abierto |
| Palabra clave: | Embryonic Development Gene Expression Regulation Animals Cell Cycle Proteins Chromosomal Proteins, Non-Histone De Lange Syndrome Embryo, Mammalian Fibroblasts Mice Mice, Knockout Protein Subunits Proto-Oncogene Proteins c-myc Cohesins |
| Sumario: | 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. |
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