Control of transcriptional pausing by biased thermal fluctuations on repetitive genomic sequences

Masahiko Imashimizu, Ariel Afek, Hiroki Takahashi, Lucyna Lubkowska, David B. Lukatsky

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

In the process of transcription elongation, RNA polymerase (RNAP) pauses at highly nonrandom positions across genomic DNA, broadly regulating transcription; however, molecular mechanisms responsible for the recognition of such pausing positions remain poorly understood. Here, using a combination of statistical mechanical modeling and high-throughput sequencing and biochemical data, we evaluate the effect of thermal fluctuations on the regulation of RNAP pausing. We demonstrate that diffusive backtracking of RNAP, which is biased by repetitive DNA sequence elements, causes transcriptional pausing. This effect stems from the increased microscopic heterogeneity of an elongation complex, and thus is entropydominated. This report shows a linkage between repetitive sequence elements encoded in the genome and regulation of RNAP pausing driven by thermal fluctuations.

Original languageEnglish
Pages (from-to)E7409-E7417
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number47
DOIs
StatePublished - 22 Nov 2016

Keywords

  • Backtracking
  • Nonconsensus protein-DNA binding
  • RNA polymerase
  • Repetitive DNA sequence elements
  • Thermal fluctuations

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