1. Inici
  2. Publicacions
  3. Disruption of NIPBL/Scc2 in Cornelia de Lange Syndrome provokes cohesin genome-wide redistribution with an impact in the transcriptome

Disruption of NIPBL/Scc2 in Cornelia de Lange Syndrome provokes cohesin genome-wide redistribution with an impact in the transcriptome

Data de publicació: Data Ahead of Print:

Autors de IIS La Fe

Autors aliens a IIS La Fe

  • Garcia, P
  • Fernandez-Hernandez, R
  • Cuadrado, A
  • Coca, I
  • Gomez, A
  • Maqueda, M
  • Latorre-Pellicer, A
  • Puisac, B
  • Ramos, FJ
  • Esteller, M
  • Mosquera, JL
  • Rodriguez, J
  • Pie, J
  • Losada, A
  • Queralt, E

Grups d'Investigació

Abstract

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. Patients with Cornelia de Lange Syndrome (CdLS) often have mutations in cohesin and its regulators; however, the molecular mechanism driving CdLS phenotypes is not well established. Here the authors reveal system skeletal organization genes are downregulated and show that cohesin and its loader Nipbl have altered and decreased genome-wide localization.

Dades de la publicació

ISSN/ISSNe:
2041-1723, 2041-1723

NATURE COMMUNICATIONS  NATURE PUBLISHING GROUP

Tipus:
Article
Pàgines:
4551-4551
PubMed:
34315879
Factor d'Impacte:
4,846 SCImago ℠
Quartil:
Q1 SCImago ℠

Cites Rebudes en Web of Science: 18

Documents

  • No hi ha documents

Mètriques

Filiacions mostrar / ocultar

Keywords

  • SISTER-CHROMATID COHESION; GENE-EXPRESSION; DNA; MUTATIONS; CTCF; COMPLEX; DOMAINS; BINDING; SCC2; ESTABLISHMENT

Campos d'Estudi

Finançament

CIBERER
fellowship "Personal Tecnico de Apoyo" - Spanish Ministry of Science, Innovation and Universities
Gobierno de Aragon
Instituto Carlos III, State Agency (European Regional Development Fund, ERDF)
MaratoTV3
Spanish Ministry of Economy, Industry and Competitiveness
Spanish Ministry of Health ISCIII-FIS

Projectes associats

RED TEMATICA DE INVESTIGACION COOPERATIVA EN CANCER (RTICC)

Investigador Principal: MIGUEL ÁNGEL SANZ ALONSO

RD12/0036/0014 . INSTITUTO DE SALUD CARLOS III . 2013

INTEGRATIVE (EPI)GENOMIC AND DRUG TARGET ANALYSIS FOR IDENTIFICATION/VALIDATION OF CLINICALLY VALUABLE BIOMARKERS TO IMPROVE THE POOR OUTCOME OF NON-SMALL CELL LUNG CANCER PATIENTS.

Investigador Principal: JUAN SANDOVAL DEL AMOR

CP13/00055 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2015

ADQUISICIÓN DE UNA PLATAFORMA BIG DATA PARA EL ANÁLISIS Y LA GESTIÓN DE DATOS MULTI-ÓMICOS Y CLÍNICOS ORIENTADA A LA MEDICINA DE PRECISIÓN.

Investigador Principal: JOSÉ VICENTE CASTELL RIPOLL

FUFE15-EE-3906 . MINISTERIO DE ECONOMIA Y COMPETITIVIDAD . 2016

IMPLANTACIÓN DE LA MEDICINA PERSONALIZADA EN ONCOLOGÍA PEDIÁTRICA: FARMACOGENÉTICA, EPIGENÉTICA, METABOLÓMICA Y LOS SISTEMAS DE INFORMACIÓN.

Investigador Principal: MARÍA JOSÉ HERRERO CERVERA

MJH-CIS-2016-01 . FUNDACION MUTUA MADRILEÑA . 2016

VALIDACIÓN/IDENTIFICACIÓN DE BIOMARCADORES EPIGENÓMICOS PARA DIAGNOSTICO PRECOZ Y RESPUESTA A FÁRMACO PARA MEJORAR EL MALA EVOLUCIÓN DE PACIENTES CON CÁNCER DE PULMÓN CÉLULA NO PEQUEÑA.

Investigador Principal: JUAN SANDOVAL DEL AMOR

PI16/00295 . INSTITUTO DE SALUD CARLOS III . 2017

Validation/Identification of clinically valuable epigenomic biomarkers for early diagnosis to improve the current poor outcome of non-small cell lung cancer patients.

Investigador Principal: JUAN SANDOVAL DEL AMOR

2017_0367_CRC_GECP_SANDOVAL . FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2017

Desarrollo de un kit epigenético para el diagnóstico no invasivo para el cáncer de pulmón.

Investigador Principal: JUAN SANDOVAL DEL AMOR

APOTIP/2019/A/004 . CONSELLERIA DE EDUCACION . 2019

Epigenetic signature for early detection in lung cancer: a clinical research with medical device and grhl2: key gene in EMT in resistance to egfr tysosine-kinase inhibitors in LC patients.

Investigador Principal: JUAN SANDOVAL DEL AMOR

PI19/00572 . INSTITUTO DE SALUD CARLOS III . 2020

PULMONOINVA. Desarrollo y valorización de un kit epigenético para el diagnóstico precoz no invasivo del cáncer de pulmón en broncoaspirados y otros fluidos

Investigador Principal: JUAN SANDOVAL DEL AMOR

INNVA1/2020/71 . AGENCIA VALENCIANA DE LA INNOVACION (AVI) . 2020

Contrato PFIS 2020. Ester Alemany Cosme

Investigador Principal: JUAN SANDOVAL DEL AMOR

FI20/00136 . INSTITUTO DE SALUD CARLOS III . 2021

Plataforma ISCIII de Dinamización e Innovación de las capacidades industriales del SNS y su transferencia efectiva al sector productivo (ITEMAS)

Investigador Principal: SILVIA SÁNCHEZ SALVO

PT20/00105 . INSTITUTO DE SALUD CARLOS III . 2021

Compartir la publicació