Continuous transcription initiation guarantees robust repair of all transcribed genes and regulatory regions
| Autor: | Matthieu D. Lavigne, Maria Fousteri, Dimitris Konstantopoulos, Anastasios Liakos |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
DNA Repair Transcription Genetic Molecular biology DNA repair Science General Physics and Astronomy RNA polymerase II Regulatory Sequences Nucleic Acid Article General Biochemistry Genetics and Molecular Biology Transcriptome 03 medical and health sciences 0302 clinical medicine Transcription (biology) Humans Promoter Regions Genetic lcsh:Science Gene Regulation of gene expression Multidisciplinary biology DNA damage and repair General Chemistry Chromatin Cell biology 030104 developmental biology Gene Expression Regulation Regulatory sequence biology.protein RNA lcsh:Q RNA Polymerase II Transcription Initiation Site Transcription 030217 neurology & neurosurgery DNA Damage |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. A transcription-driven cellular response is activated upon UV stress. Here the authors reveal mechanistic insights into the regulatory process affecting transcription and chromatin dynamics, showing how maintaining Pol II firing safeguards the integrity of cells’ transcriptome |
| Databáze: | OpenAIRE |
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