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Nat Cell Biol. 2017 May;19(5):421-432. doi: 10.1038/ncb3499. Epub 2017 Apr 3.

ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes.

Author information

1
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Nikolaou Plastira 100, 70013 Heraklion, Crete, Greece.
2
Department of Biology, University of Crete, Vassilika Vouton, GR71409 Heraklion, Crete, Greece.
3
Division of Molecular Oncology, Biomedical Sciences Research Center 'Alexander Fleming', GR 16672 Vari, Greece.

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.

PMID:
28368372
DOI:
10.1038/ncb3499
[Indexed for MEDLINE]

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