The xeroderma pigmentosum factors XPG and XPF are DNA repair endonucleases; however, various roles in transcription have also been proposed. Le May et al. investigated further by knocking down xeroderma pigmentosum factors in HeLa cells and studying the effects on the induction of the RARB gene (which is induced by retinoic acid) and on various molecular features at the RARB locus. They found that XPG and XPF are required for optimal RARB transcription by a complex mechanism involving single-strand DNA break generation, DNA demethylation, CTCF transcription factor recruitment and chromosomal looping to bring the promoter and terminator sequences into proximity.