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Phenotypic Consequences of Promoter-Mediated Transcriptional Noise

  • William J. Blake
  • , Gábor Balázsi
  • , Michael A. Kohanski
  • , Farren J. Isaacs
  • , Kevin F. Murphy
  • , Yina Kuang
  • , Charles R. Cantor
  • , David R. Walt
  • , James J. Collins
  • Boston University
  • Harvard University
  • Tufts University

Research output: Contribution to journalArticlepeer-review

510 Scopus citations

Abstract

A more complete understanding of the causes and effects of cell-cell variability in gene expression is needed to elucidate whether the resulting phenotypes are disadvantageous or confer some adaptive advantage. Here we show that increased variability in gene expression, affected by the sequence of the TATA box, can be beneficial after an acute change in environmental conditions. We rationally introduce mutations within the TATA region of an engineered Saccharomyces cerevisiae GAL1 promoter and measure promoter responses that can be characterized as being either highly variable and rapid or steady and slow. We computationally illustrate how a stable transcription scaffold can result in "bursts" of gene expression, enabling rapid individual cell responses in the transient and increased cell-cell variability at steady state. We experimentally verify computational predictions that the rapid response and increased cell-cell variability enabled by TATA-containing promoters confer a clear benefit in the face of an acute environmental stress.

Original languageEnglish
Pages (from-to)853-865
Number of pages13
JournalMolecular Cell
Volume24
Issue number6
DOIs
StatePublished - Dec 28 2006

Keywords

  • DNA

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