Defective transcription initiation causes postnatal growth failure in a mouse model of nucleotide excision repair (NER) progeria.

ABSTRACT: Nucleotide excision repair (NER) defects are associated with cancer, developmental disorders and neurodegeneration. However, with the exception of cancer, the links between defects in NER and developmental abnormalities are not well understood. Here, we show that the ERCC1-XPF NER endonuclease assembles on active promoters in vivo and facilitates chromatin modifications for transcription during mammalian development. We find that Ercc1(-/-) mice demonstrate striking physiological, metabolic and gene expression parallels with Taf10(-/-) animals carrying a liver-specific transcription factor II D (TFIID) defect in transcription initiation. Promoter occupancy studies combined with expression profiling in the liver and in vitro differentiation cell assays reveal that ERCC1-XPF interacts with T

SUBMITTER: Kamileri I 

PROVIDER: S-EPMC3286994 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature