title: Histone methyltransferase DOT1L drives recovery of gene expression after a genotoxic attack.
abstract: UV-induced DNA damage causes repression of RNA synthesis. Following the removal of DNA lesions, transcription recovery operates through a process that is not understood yet. Here we show that knocking-out of the histone methyltransferase DOT1L in mouse embryonic fibroblasts (MEF(DOT1L)) leads to a UV hypersensitivity coupled to a deficient recovery of transcription initiation after UV irradiation. However, DOT1L is not implicated in the removal of the UV-induced DNA damage by the nucleotide excision repair pathway. Using FRAP and ChIP experiments we established that DOT1L promotes the formation of the pre-initiation complex on the promoters of UV-repressed genes and the appearance of transcriptionally active chromatin marks. Treatment with Trichostatin A, relaxing chromatin, recovers both transcription initiation and UV-survival. Our data suggest that DOT1L secures an open chromatin structure in order to reactivate RNA Pol II transcription initiation after a genotoxic attack.
authors.affiliation: IGBMC, Department of Functional Genomics and Cancer, CNRS/INSERM/Université de Strasbourg, C. U. Strasbourg, France.
authors.forename: Valentyn
authors.initials: V
authors.lastname: Oksenych
authors.forename: Alexander
authors.initials: A
authors.lastname: Zhovmer
authors.forename: Salim
authors.initials: S
authors.lastname: Ziani
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Mari
authors.forename: Jitka
authors.initials: J
authors.lastname: Eberova
authors.forename: Tiziana
authors.initials: T
authors.lastname: Nardo
authors.forename: Miria
authors.initials: M
authors.lastname: Stefanini
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Giglia-Mari
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Egly
authors.forename: Frédéric
authors.initials: F
authors.lastname: Coin
mesh_terms: D000818:Animals; D002843:Chromatin / Q000235:genetics* / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D011495:Histone-Lysine N-Methyltransferase; D006877:Hydroxamic Acids / Q000494:pharmacology; D006967:Hypersensitivity; D008780:Methyltransferases / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D012319:RNA Polymerase II / Q000378:metabolism; D015533:Transcriptional Activation; D014466:Ultraviolet Rays
chemical_list: D002843:Chromatin; D006877:Hydroxamic Acids; C012589:trichostatin A; C481527:Dot1l protein, mouse; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D012319:RNA Polymerase II