1. Computational and Systems Biology
  2. Chromosomes and Gene Expression
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Transcription mediated insulation and interference direct gene cluster expression switches

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Cite this article as: eLife 2014;3:e03635 doi: 10.7554/eLife.03635

Abstract

In yeast, many tandemly arranged genes show peak expression in different phases of the metabolic cycle (YMC) or in different carbon sources, indicative of regulation by a bi-modal switch, but it is not clear how these switches are controlled. Using native elongating transcript analysis (NET-seq), we show that transcription itself is a component of bi-modal switches, facilitating reciprocal expression in gene clusters. HMS2, encoding a growth-regulated transcription factor, switches between sense- or antisense-dominant states that also coordinate up- and down-regulation of transcription at neighbouring genes. Engineering HMS2 reveals alternative mono-, di- or tri-cistronic and antisense transcription units (TUs), using different promoter and terminator combinations, that underlie state-switching. Promoters or terminators are excluded from functional TUs by read-through transcriptional interference, while antisense TUs insulate downstream genes from interference. We propose that the balance of transcriptional insulation and interference at gene clusters facilitates gene expression switches during intracellular and extracellular environmental change.

Article and author information

Author details

  1. Tania Nguyen

    University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  2. Harry Fischl

    University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  3. Françoise S Howe

    University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  4. Ronja Woloszczuk

    University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  5. Ana Serra Barros

    University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  6. Zhenyu Xu

    European Molecular Biology Laboratory, Heidelberg, Germany
    Competing interests
    No competing interests declared.
  7. David Brown

    University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  8. Struan C Murray

    University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  9. Simon Haenni

    University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  10. James M Halstead

    University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  11. Leigh O'Connor

    University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  12. Gergana Shipkovenska

    University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  13. Lars M Steinmeetz

    European Molecular Biology Laboratory, Heidelberg, Germany
    Competing interests
    No competing interests declared.
  14. Jane Mellor

    University of Oxford, Oxford, United Kingdom
    For correspondence
    jane.mellor@bioch.ox.ac.uk
    Competing interests
    Jane Mellor, I am an advisor to Oxford Biodynamics Ltd and Sibelius Ltd and sit on the board of Chronos Therapeutics. OBD provided funding for this work but like all the funders, had no say in the design or outcome of the research and do not benefit in any way from this research.

Reviewing Editor

  1. Joaquin M Espinosa, Howard Hughes Medical Institute, University of Colorado, United States

Publication history

  1. Received: June 8, 2014
  2. Accepted: November 17, 2014
  3. Accepted Manuscript published: November 19, 2014 (version 1)
  4. Version of Record published: December 24, 2014 (version 2)

Copyright

© 2014, Nguyen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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