117323 20230519145359.0 doi 10.1038/s41467-021-24808-z sideral 125754 ART-2021-125754 eng Garcia, Patricia Disruption of NIPBL/Scc2 in Cornelia de Lange Syndrome provokes cohesin genome-wide redistribution with an impact in the transcriptome 2021 Access copy available to the general public Unrestricted 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. info:eu-repo/grantAgreement/ES/DGA/B32-17R info:eu-repo/grantAgreement/ES/FIS/PI19-01860 info:eu-repo/grantAgreement/ES/ISCIII/CA18-00045 info:eu-repo/grantAgreement/ES/ISCIII/PI19-01860 info:eu-repo/grantAgreement/ES/MICIU/PTA2018-016371-I info:eu-repo/grantAgreement/ES/MINECO/BFU2013-43132-P info:eu-repo/grantAgreement/ES/MINECO/BFU2016-77975-R info:eu-repo/grantAgreement/ES/MINECO/BFU2016-79841 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 17.694 2021 MULTIDISCIPLINARY SCIENCES 6 / 74 = 0.081 2021 Q1 T1 4.846 2021 Chemistry (miscellaneous) 2021 Q1 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2021 Q1 23.2 2021 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Fernandez-Hernandez, Rita Cuadrado, Ana Coca, Ignacio Gomez, Antonio Maqueda, Maria Latorre-Pellicer, Ana Universidad de Zaragoza (orcid)0000-0002-4703-6620 Puisac, Beatriz Ramos, Feliciano J. Universidad de Zaragoza (orcid)0000-0002-5732-2209 Sandoval, Juan Esteller, Manel Mosquera, Jose Luis Rodriguez, Jairo Pié, J. Universidad de Zaragoza (orcid)0000-0003-3203-6254 Losada, Ana Queralt, Ethel 1012 410 Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Fisiología 1011 670 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Pediatría 12 (2021), 4551 [15 pp.] Nature communications 2041-1723 3594454 http://zaguan.unizar.es/record/117323/files/texto_completo.pdf Versión publicada 2124894 http://zaguan.unizar.es/record/117323/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:117323 articulos driver 2023-05-18-13:36:25 ARTICLE