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Biochim Biophys Acta. 2013 Dec;1832(12):2097-102. doi: 10.1016/j.bbadis.2013.07.020. Epub 2013 Aug 3.

Reduction of Nipbl impairs cohesin loading locally and affects transcription but not cohesion-dependent functions in a mouse model of Cornelia de Lange Syndrome.

Author information

1
Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain.

Abstract

Cornelia de Lange Syndrome (CdLS) is a genetic disorder linked to mutations in cohesin and its regulators. To date, it is unclear which function of cohesin is more relevant to the pathology of the syndrome. A mouse heterozygous for the gene encoding the cohesin loader Nipbl recapitulates many features of CdLS. We have carefully examined Nipbl deficient cells and here report that they have robust cohesion all along the chromosome. DNA replication, DNA repair and chromosome segregation are carried out efficiently in these cells. While bulk cohesin loading is unperturbed, binding to certain promoters such as the Protocadherin genes in brain is notably affected and alters gene expression. These results provide further support for the idea that developmental defects in CdLS are caused by deregulated transcription and not by malfunction of cohesion-related processes.

KEYWORDS:

Cohesin; Cornelia de Lange Syndrome; Mouse model; Nibpl; Transcription

PMID:
23920377
PMCID:
PMC3825806
DOI:
10.1016/j.bbadis.2013.07.020
[Indexed for MEDLINE]
Free PMC Article
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