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Nat Struct Mol Biol. 2014 Jan;21(1):88-94. doi: 10.1038/nsmb.2723. Epub 2013 Dec 8.

Transcription-generated torsional stress destabilizes nucleosomes.

Author information

1
1] Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, USA.
2
1] Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Abstract

As RNA polymerase II (Pol II) transcribes a gene, it encounters an array of well-ordered nucleosomes. How it traverses through this array in vivo remains unresolved. One model proposes that torsional stress generated during transcription destabilizes nucleosomes ahead of Pol II. Here, we describe a method for high-resolution mapping of underwound DNA, using next-generation sequencing, and show that torsion is correlated with gene expression in Drosophila melanogaster cells. Accumulation of torsional stress, through topoisomerase inhibition, results in increased Pol II at transcription start sites. Whereas topoisomerase I inhibition results in increased nascent RNA transcripts, topoisomerase II inhibition causes little change. Despite the different effects on Pol II elongation, topoisomerase inhibition results in increased nucleosome turnover and salt solubility within gene bodies, thus suggesting that the elongation-independent effects of torsional stress on nucleosome dynamics contributes to the destabilization of nucleosomes.

PMID:
24317489
PMCID:
PMC3947361
DOI:
10.1038/nsmb.2723
[Indexed for MEDLINE]
Free PMC Article

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