Genomics

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297

UVB induces a major genome-wide rearrangement of RNA polymerase II at transcribed human genes


ABSTRACT: Abstract Background: Faithful transcription of DNA is constantly threatened by different endogenous and environmental genotoxic effects. Transcription coupled repair has been described to 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. However, the precise mechanism by which RNA polymerase II (Pol II) transcription is affected following UV irradiation during the repair processes genome-wide is not well understood. Results: We investigated the effect of a non-lethal dose of UVB on global DNA-bound Pol II distribution in human cells. We find that about 90% of the promoters of expressed genes show reduced Pol II occupancy 2-4 hours following UVB irradiation, and that the presence of Pol II is restored to “normal”, or higher, levels 5-6 hours after irradiation. We also identified a smaller set of genes, where the presence of Pol II at the promoter regions does not decrease after UVB irradiation, but often increases throughout the entire transcription units. Interestingly, at promoters, where Pol II promoter clearance occurs, TFIIH but not TBP follows the behavior of Pol II suggesting that at these genes TFIIH may be sequestered for DNA repair upon UVB treatment. Conclusions: Thus, our study reveals a global negative regulatory mechanism that targets Pol II transcription initiation on the large majority of transcribed genes following sublethal UVB irradiation, and a small subset of genes (including regulators of repair, cell growth and survival), where Pol II escapes this negative regulation. Following genome-wide RNA Polymerase II redistribution over time upon UVB irradiation

ORGANISM(S): Homo sapiens  

SUBMITTER: Imre Boros   David Umlauf  Akos Gyenis  Tao Ye  Làszlò Tora  Zsuzsanna Ujfaludi  Ákos Gyenis 

PROVIDER: E-GEOD-52789 | ArrayExpress | 2014-07-25

SECONDARY ACCESSION(S): SRP033363GSE52789PRJNA230028

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

UVB induces a genome-wide acting negative regulatory mechanism that operates at the level of transcription initiation in human cells.

Gyenis Akos A   Umlauf David D   Ujfaludi Zsuzsanna Z   Boros Imre I   Ye Tao T   Tora Làszlò L  

PLoS genetics 20140724 7


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  ...[more]

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