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.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Oksenych V,Zhovmer A,Ziani S,Mari PO,Eberova J,Nardo T,Stefanini M,Giglia-Mari G,Egly JM,Coin F

doi

10.1371/journal.pgen.1003611

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

e1003611

issue

7

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-13-00345

journal_volume

9

pub_type

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