2026-07-21T14:57:27Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/132602024-11-28T18:14:28Zcom_20.500.12105_2173com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19597col_20.500.12105_16962col_20.500.12105_16975
Repisalud
author
Garcia, Patricia
author
Fernandez-Hernandez, Rita
author
Cuadrado, Ana
author
Coca, Ignacio
author
Gomez, Antonio
author
Maqueda, Maria
author
Latorre-Pellicer, Ana
author
Puisac, Beatriz
author
Ramos, Feliciano J
author
Sandoval, Juan
author
Esteller, Manel
author
Mosquera, Jose Luis
author
Rodriguez, Jairo
author
Pié, J
author
Queralt, Ethel
author
Losada, Ana
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fundación La Marató TV3
funder
Government of Catalonia (España)
funder
Instituto de Salud Carlos III
2021-07-30T11:43:19Z
2021-07-30T11:43:19Z
2021-07-27
Nat Commun. 2021 ;12(1):4551.
10.1038/s41467-021-24808-z
2041-1723
Nature communications
34315879
http://hdl.handle.net/20.500.12105/13260
Cornelia de Lange syndrome (CdLS) is a rare disease affecting multiple organs and systems during development. Mutations in the cohesin loader, NIPBL/Scc2, were first described and are the most frequent in clinically diagnosed CdLS patients. The molecular mechanisms driving CdLS phenotypes are not understood. In addition to its canonical role in sister chromatid cohesion, cohesin is implicated in the spatial organization of the genome. Here, we investigate the transcriptome of CdLS patient-derived primary fibroblasts and observe the downregulation of genes involved in development and system skeletal organization, providing a link to the developmental alterations and limb abnormalities characteristic of CdLS patients. Genome-wide distribution studies demonstrate a global reduction of NIPBL at the NIPBL-associated high GC content regions in CdLS-derived cells. In addition, cohesin accumulates at NIPBL-occupied sites at CpG islands potentially due to reduced cohesin translocation along chromosomes, and fewer cohesin peaks colocalize with CTCF.
eng
Cornelia de Lange Syndrome
Transcriptome
NIPBL/Scc2
Disruption of NIPBL/Scc2 in Cornelia de Lange Syndrome provokes cohesin genome-wide redistribution with an impact in the transcriptome.
journal article
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