Τίτλος:
Continuous transcription initiation guarantees robust repair of all transcribed genes and regulatory regions
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Inhibition of transcription caused by DNA damage-impaired RNA polymerase II (Pol II) elongation conceals a local increase in de novo transcription, slowly progressing from Transcription Start Sites (TSSs) to gene ends. Although associated with accelerated repair of Pol II-encountered lesions and limited mutagenesis, it is still unclear how this mechanism is maintained during genotoxic stress-recovery. Here we uncover a widespread gain in chromatin accessibility and preservation of the active H3K27ac mark after UV-irradiation. The concomitant increase in Pol II escape from promoter-proximal pause (PPP) sites of most active genes, PROMPTs and enhancer RNAs favors unrestrained initiation, as evidenced by the synthesis of nascent RNAs including start RNAs. Accordingly, drug-inhibition of PPP-release replenishes levels of pre-initiating Pol II at TSSs after UV. Our data show that such continuous engagement of Pol II molecules ensures maximal transcription-driven repair throughout expressed genes and regulatory loci. Importantly, revealing this unanticipated regulatory layer of UV-response provides physiological relevant traction to the emerging concept that Pol II initiation rate is determined by pause-release dynamics. © 2020, The Author(s).
Συγγραφείς:
Liakos, A.
Konstantopoulos, D.
Lavigne, M.D.
Fousteri, M.
Περιοδικό:
Nature Communications
Εκδότης:
Institute of Geographic Sciences and Natural Resources Research
Λέξεις-κλειδιά:
messenger RNA; RNA polymerase II; RNA; RNA polymerase II, DNA; gene; genetic analysis; genotoxicity; pigment, Article; controlled study; DNA damage; DNA damage response; DNA template; excision repair; gene expression; gene locus; histone modification; human; nucleosome; promoter region; RNA synthesis; transcription elongation; transcription initiation; transcription initiation site; ultraviolet irradiation; chromatin; DNA damage; DNA repair; gene expression regulation; genetic transcription; genetics; metabolism; regulatory sequence; transcription initiation site, Chromatin; DNA Damage; DNA Repair; Gene Expression Regulation; Humans; Promoter Regions, Genetic; Regulatory Sequences, Nucleic Acid; RNA; RNA Polymerase II; Transcription Initiation Site; Transcription, Genetic
DOI:
10.1038/s41467-020-14566-9
