title: ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes.
abstract: 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.
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Nikolaou Plastira 100, 70013 Heraklion, Crete, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Chatzinikolaou
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Nikolaou Plastira 100, 70013 Heraklion, Crete, Greece.|Department of Biology, University of Crete, Vassilika Vouton, GR71409 Heraklion, Crete, Greece.
authors.forename: Zivkos
authors.initials: Z
authors.lastname: Apostolou
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Nikolaou Plastira 100, 70013 Heraklion, Crete, Greece.
authors.forename: Tamara
authors.initials: T
authors.lastname: Aid-Pavlidis
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Nikolaou Plastira 100, 70013 Heraklion, Crete, Greece.|Department of Biology, University of Crete, Vassilika Vouton, GR71409 Heraklion, Crete, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Ioannidou
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Nikolaou Plastira 100, 70013 Heraklion, Crete, Greece.
authors.forename: Ismene
authors.initials: I
authors.lastname: Karakasilioti
authors.affiliation: Department of Biology, University of Crete, Vassilika Vouton, GR71409 Heraklion, Crete, Greece.|Division of Molecular Oncology, Biomedical Sciences Research Center 'Alexander Fleming', GR 16672 Vari, Greece.
authors.forename: Giorgio L
authors.initials: GL
authors.lastname: Papadopoulos
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Nikolaou Plastira 100, 70013 Heraklion, Crete, Greece.
authors.forename: Michalis
authors.initials: M
authors.lastname: Aivaliotis
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Nikolaou Plastira 100, 70013 Heraklion, Crete, Greece.|Department of Biology, University of Crete, Vassilika Vouton, GR71409 Heraklion, Crete, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Tsekrekou
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Nikolaou Plastira 100, 70013 Heraklion, Crete, Greece.|Division of Molecular Oncology, Biomedical Sciences Research Center 'Alexander Fleming', GR 16672 Vari, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Strouboulis
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Nikolaou Plastira 100, 70013 Heraklion, Crete, Greece.
authors.forename: Theodore
authors.initials: T
authors.lastname: Kosteas
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Nikolaou Plastira 100, 70013 Heraklion, Crete, Greece.|Department of Biology, University of Crete, Vassilika Vouton, GR71409 Heraklion, Crete, Greece.
authors.forename: George A
authors.identifier: http://orcid.org/0000-0002-3200-5004
authors.initials: GA
authors.lastname: Garinis
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D018920:Coculture Techniques; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000201:enzymology; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D018392:Genomic Imprinting; D005838:Genotype; D006657:Histones / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D000075924:X-linked Nuclear Protein; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1
chemical_list: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D011508:Chondroitin Sulfate Proteoglycans; D002868:Chromosomal Proteins, Non-Histone; D004265:DNA Helicases; D004268:DNA-Binding Proteins; D004720:Endonucleases; D006657:Histones; D009687:Nuclear Proteins; D012097:Repressor Proteins; D000075924:X-linked Nuclear Protein; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1; C492317:SMC3 protein, mouse; C000619698:Ctcf protein, mouse; C489326:Mbd2 protein, mouse; C095888:xeroderma pigmentosum group F protein; C499360:Ercc1 protein, mouse; C490462:Atrx protein, mouse