Control of transcription initiation by biased thermal fluctuations on repetitive genomic sequences

Masahiko Imashimizu, Yuji Tokunaga, Ariel Afek, Hiroki Takahashi, Nobuo Shimamoto, David B. Lukatsky

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

In the process of transcription initiation by RNA polymerase, promoter DNA sequences affect multiple reaction pathways determining the productivity of transcription. However, the question of how the molecular mechanism of transcription initiation depends on the sequence properties of promoter DNA remains poorly understood. Here, combining the statistical mechanical approach with high-throughput sequencing results, we characterize abortive transcription and pausing during transcription initiation by Escherichia coli RNA polymerase at a genome-wide level. Our results suggest that initially transcribed sequences, when enriched with thymine bases, contain the signal for inducing abortive transcription, whereas certain repetitive sequence elements embedded in promoter regions constitute the signal for inducing pausing. Both signals decrease the productivity of transcription initiation. Based on solution NMR and in vitro transcription measurements, we suggest that repetitive sequence elements within the promoter DNA modulate the nonlocal base pair stability of its double-stranded form. This stability profoundly influences the reaction coordinates of the productive initiation via pausing.

Original languageEnglish
Article number1299
Pages (from-to)1-22
Number of pages22
JournalBiomolecules
Volume10
Issue number9
DOIs
StatePublished - 1 Sep 2020

Keywords

  • Abortive initiation
  • Nonlocal base pair stability
  • Pausing
  • Promoter sequences
  • RNA polymerase
  • Repetitive sequences
  • Thermal fluctuations

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Control of transcription initiation by biased thermal fluctuations on repetitive genomic sequences'. Together they form a unique fingerprint.

Cite this