XPC is an RNA polymerase II cofactor recruiting ATAC to promoters by interacting with E2F1

• DOI: 10.1038/s41467-018-05010-0
• Publication Date: 2018-06-28T15:02:14Z
• Authors: B. Bidon; I. Iltis; M. Semer; Z. Nagy; A. Larnicol; A. Cribier; M. Benkirane; F. Coin; J-M. Egly; N. Le May
• Keywords: Xeroderma Pigmentosum; 0303 health sciences; DNA Repair; [SDV]Life Sciences [q-bio]; Science; Q; Primary Cell Culture; Acetylation; Fibroblasts; Article; DNA-Binding Proteins; Histones; 03 medical and health sciences; [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]; Humans; [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology; RNA Polymerase II; Promoter Regions, Genetic; Protein Processing, Post-Translational; E2F1 Transcription Factor; DNA Damage; HeLa Cells; Histone Acetyltransferases; Protein Binding

AbstractThe 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.