ERCC1–XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes
| Autor: | George A. Garinis, Michalis Aivaliotis, John Strouboulis, Georgia Chatzinikolaou, Anna Ioannidou, Giorgio L. Papadopoulos, Zivkos Apostolou, Theodore Kosteas, Tamara Aid-Pavlidis, Ismene Karakasilioti, Maria Tsekrekou |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
CCCTC-Binding Factor X-linked Nuclear Protein Mice 129 Strain DNA Repair Genotype Chromosomal Proteins Non-Histone Cell Cycle Proteins Mice Transgenic Insulator (genetics) Biology Histones Genomic Imprinting 03 medical and health sciences Animals Gene Silencing Promoter Regions Genetic Cells Cultured ATRX Genetics Cohesin Age Factors DNA Helicases Gene Expression Regulation Developmental Nuclear Proteins Cell Biology Fibroblasts Endonucleases Coculture Techniques Chromatin Cell biology DNA-Binding Proteins Mice Inbred C57BL Repressor Proteins Phenotype 030104 developmental biology Animals Newborn Chondroitin Sulfate Proteoglycans Liver CTCF DNA methylation Genomic imprinting DNA Damage Nucleotide excision repair |
| Zdroj: | Nature Cell Biology |
| ISSN: | 1465-7392 |
| DOI: | 10.1038/ncb3499 |
| Popis: | Inborn defects in DNA repair are associated with complex developmental disorders whose causal mechanisms are poorly understood. Using an in vivo biotinylation tagging approach in mice, we show that the nucleotide excision repair (NER) structure-specific endonuclease ERCC1-XPF complex interacts with the insulator binding protein CTCF, the cohesin subunits SMC1A and SMC3 and with MBD2; the factors co-localize with ATRX at the promoters and control regions (ICRs) of imprinted genes during postnatal hepatic development. Loss of Ercc1 or exposure to MMC triggers the localization of CTCF to heterochromatin, the dissociation of the CTCF-cohesin complex and ATRX from promoters and ICRs, altered histone marks and the aberrant developmental expression of imprinted genes without altering DNA methylation. We propose that ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders. |
| Databáze: | OpenAIRE |
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