Abstract
The DNA damage sensor XPC is involved in nucleotide excision repair. Here we show that in the absence of damage, XPC co-localizes with RNA polymerase II (Pol II) and active post-translational histone modifications marks on a subset of class II promoters in human fibroblasts. XPC depletion triggers specific gene down-expression due to a drop in the deposition of histone H3K9 acetylation mark and pre-initiation complex formation. XPC interacts with the histone acetyltransferase KAT2A and specifically triggers the recruitment of the KAT2A-containing ATAC complex to the promoters of down-expressed genes. We show that a strong E2F1 signature characterizes the XPC/KAT2A-bound promoters and that XPC interacts with E2F1 and promotes its binding to its DNA element. Our data reveal that the DNA repair factor XPC is also an RNA polymerase II cofactor recruiting the ATAC coactivator complex to promoters by interacting with the DNA binding transcription factor E2F1.
Highlights
The DNA damage sensor XPC is involved in nucleotide excision repair
We observed a correlation at 6 h post all-trans retinoic acid (ATRA) treatment between RARß2 mRNA induction and recruitment of the transcriptional machinery, together with the nucleotide excision repair (NER) factors (XPC, XPA, and XPG) at the RARß2 promoter in both Xeroderma pigmentosum (XP)-CWT and XP-CMUT cells (Fig. 1b and Supplementary Figure 1A)
We performed chromatin immunoprecipitation (ChIP) followed by highthroughput DNA sequencing (ChIP-seq) in both XP-CWT and XPCDEL cells that were treated during 6 h with ATRA using antibodies directed against green fluorescent protein (GFP) and polymerase II (Pol II)
Summary
The DNA damage sensor XPC is involved in nucleotide excision repair. Here we show that in the absence of damage, XPC co-localizes with RNA polymerase II (Pol II) and active posttranslational histone modifications marks on a subset of class II promoters in human fibroblasts. A link between DNA repair and transcription was first established after the discovery of a nucleotide excision repair (NER) sub-pathway removing DNA lesions located on the actively transcribed strand blocking elongating RNA polymerase II (Pol II) called the transcription coupled repair (TCR)[1]. This was followed by the characterization of the basal transcription TFIIH as a NER factor involved both in TCR and in global genome repair (GGR), eliminating DNA damage from the entire genome[2,3]. The involvement of XPC in transcription is established, its mechanistic role remains largely elusive as well as its transcriptional partners in the pre-initiation complex
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