UVB Induces a Genome-Wide Acting Negative Regulatory Mechanism That Operates at the Level of Transcription Initiation in Human Cells

Ákos Gyenis, David Umlauf, Zsuzsanna Újfaludi, I. Boros, Tao Ye, Làszlò Tora

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Faithful transcription of DNA is constantly threatened by different endogenous and environmental genotoxic effects. Transcription coupled repair (TCR) has been described to stop transcription and quickly remove DNA lesions from the transcribed strand of active genes, permitting rapid resumption of blocked transcription. This repair mechanism has been well characterized in the past using individual target genes. Moreover, numerous efforts investigated the fate of blocked RNA polymerase II (Pol II) during DNA repair mechanisms and suggested that stopped Pol II complexes can either backtrack, be removed and degraded or bypass the lesions to allow TCR. We investigated the effect of a non-lethal dose of UVB on global DNA-bound Pol II distribution in human cells. We found that the used UVB dose did not induce Pol II degradation however surprisingly at about 93% of the promoters of all expressed genes Pol II occupancy was seriously reduced 2-4 hours following UVB irradiation. The presence of Pol II at these cleared promoters was restored 5-6 hours after irradiation, indicating that the negative regulation is very dynamic. We also identified a small set of genes (including several p53 regulated genes), where the UVB-induced Pol II clearing did not operate. Interestingly, at promoters, where Pol II promoter clearance occurs, TFIIH, but not TBP, follows the behavior of Pol II, suggesting that at these genes upon UVB treatment TFIIH is sequestered for DNA repair by the TCR machinery. In agreement, in cells where the TCR factor, the Cockayne Syndrome B protein, was depleted UVB did not induce Pol II and TFIIH clearance at promoters. Thus, our study reveals a UVB induced negative regulatory mechanism that targets Pol II transcription initiation on the large majority of transcribed gene promoters, and a small subset of genes, where Pol II escapes this negative regulation.

Original languageEnglish
Article numbere1004483
JournalPLoS Genetics
Volume10
Issue number7
DOIs
Publication statusPublished - 2014

Fingerprint

repair
genome
transcription (genetics)
Genome
gene
promoter regions
Genes
DNA
genes
cells
DNA Repair
DNA repair
lesion
lesions (animal)
DNA Polymerase II
Cockayne Syndrome
irradiation
equipment maintenance and repair
RNA Polymerase II
p53 Genes

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)
  • Medicine(all)

Cite this

UVB Induces a Genome-Wide Acting Negative Regulatory Mechanism That Operates at the Level of Transcription Initiation in Human Cells. / Gyenis, Ákos; Umlauf, David; Újfaludi, Zsuzsanna; Boros, I.; Ye, Tao; Tora, Làszlò.

In: PLoS Genetics, Vol. 10, No. 7, e1004483, 2014.

Research output: Contribution to journalArticle

Gyenis, Ákos ; Umlauf, David ; Újfaludi, Zsuzsanna ; Boros, I. ; Ye, Tao ; Tora, Làszlò. / UVB Induces a Genome-Wide Acting Negative Regulatory Mechanism That Operates at the Level of Transcription Initiation in Human Cells. In: PLoS Genetics. 2014 ; Vol. 10, No. 7.
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