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.