Oxidative stress rapidly stabilizes promoter-proximal paused Pol II across the human genome

Kyle A Nilson; Christine K Lawson; Nicholas J Mullen; Christopher B Ball; Benjamin M Spector; Jeffery L Meier; David H Price

doi:10.1093/nar/gkx724

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Oxidative stress rapidly stabilizes promoter-proximal paused Pol II across the human genome

Journal article

Open access

Peer reviewed

Oxidative stress rapidly stabilizes promoter-proximal paused Pol II across the human genome

Kyle A Nilson, Christine K Lawson, Nicholas J Mullen, Christopher B Ball, Benjamin M Spector, Jeffery L Meier and David H Price

Nucleic acids research, Vol.45(19), pp.11088-11105

11/02/2017

DOI: 10.1093/nar/gkx724

PMCID: PMC5737879

PMID: 28977633

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Abstract

Oxidative stress has pervasive effects on cells but how they respond transcriptionally upon the initial insult is incompletely understood. We developed a nuclear walk-on assay that semi-globally quantifies nascent transcripts in promoter-proximal paused RNA polymerase II (Pol II). Using this assay in conjunction with ChIP-Seq, in vitro transcription, and a chromatin retention assay, we show that within a minute, hydrogen peroxide causes accumulation of Pol II near promoters and enhancers that can best be explained by a rapid decrease in termination. Some of the accumulated polymerases slowly move or 'creep' downstream. This second effect is correlated with and probably results from loss of NELF association and function. Notably, both effects were independent of DNA damage and ADP-ribosylation. Our results demonstrate the unexpected speed at which a global transcriptional response can occur. The findings provide strong support for the residence time of paused Pol II elongation complexes being much shorter than estimated from previous studies.

Transcriptional Elongation Factors - metabolism

Transcription, Genetic - drug effects

Oxidants - pharmacology

Oxidative Stress

RNA Interference

Humans

Hydrogen Peroxide - pharmacology

Transcriptional Elongation Factors - genetics

HeLa Cells

RNA Polymerase II - metabolism

Promoter Regions, Genetic - genetics

Genome, Human - genetics

Details

Title: Subtitle: Oxidative stress rapidly stabilizes promoter-proximal paused Pol II across the human genome
Creators: Kyle A Nilson - Molecular and Cellular Biology Program, University of Iowa, Iowa City, IA 52242, USA
Christine K Lawson - Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA
Nicholas J Mullen - Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA
Christopher B Ball - Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA
Benjamin M Spector - Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA
Jeffery L Meier - Department of Internal Medicine, University of Iowa and Veterans Affairs Health Care System, Iowa City, IA 52242, USA
David H Price - Molecular and Cellular Biology Program, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Nucleic acids research, Vol.45(19), pp.11088-11105
Publisher: England
DOI: 10.1093/nar/gkx724
PMID: 28977633
PMCID: PMC5737879
ISSN: 0305-1048
eISSN: 1362-4962
Grant note: R01 GM113935 / NIGMS NIH HHS R01 GM035500 / NIGMS NIH HHS
Language: English
Date published: 11/02/2017
Academic Unit: Epidemiology; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9984024545502771

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