Role of the pre-initiation complex in Mediator recruitment and dynamics

  1. Elisabeth R Knoll
  2. Z Iris Zhu
  3. Debasish Sarkar
  4. David Landsman
  5. Randall H Morse  Is a corresponding author
  1. University at Albany School of Public Health, United States
  2. National Center for Biotechnology Information, National Library of Medicine, National Institute of Health, United States
  3. New York State Department of Health, United States

Abstract

The Mediator complex stimulates the cooperative assembly of a pre-initiation complex (PIC) and recruitment of RNA Polymerase II (Pol II) for gene activation. The core Mediator complex is organized into head, middle, and tail modules, and in budding yeast (Saccharomyces cerevisiae), Mediator recruitment has generally been ascribed to sequence-specific activators engaging the tail module triad of Med2-Med3-Med15 at upstream activating sequences (UASs). We show that yeast lacking Med2-Med3-Med15 are viable and that Mediator and PolII are recruited to promoters genome-wide in these cells, albeit at reduced levels. To test whether Mediator might alternatively be recruited via interactions with the PIC, we examined Mediator association genome-wide after depleting PIC components. We found that depletion of Taf1, Rpb3, and TBP profoundly affected Mediator association at active gene promoters, with TBP being critical for transit of Mediator from UAS to promoter, while Pol II and Taf1 stabilize Mediator association at proximal promoters.

Data availability

Data from ChIP-seq and RNA-seq experiments have been deposited at the NCBI Short Read Archive under project number PRJNA413080.

The following data sets were generated

Article and author information

Author details

  1. Elisabeth R Knoll

    Department of Biomedical Sciences, University at Albany School of Public Health, Albany, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1083-6472
  2. Z Iris Zhu

    Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institute of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Debasish Sarkar

    Wadsworth Center, New York State Department of Health, Albany, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. David Landsman

    Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institute of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9819-6675
  5. Randall H Morse

    Department of Biomedical Sciences, University at Albany School of Public Health, Albany, United States
    For correspondence
    randall.morse@health.ny.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0000-8718

Funding

National Science Foundation (MCB1516839)

  • Elisabeth R Knoll
  • Debasish Sarkar
  • Randall H Morse

National Institutes of Health (Intramural program)

  • Z Iris Zhu
  • David Landsman

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Alan G Hinnebusch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States

Publication history

  1. Received: June 28, 2018
  2. Accepted: December 12, 2018
  3. Accepted Manuscript published: December 12, 2018 (version 1)
  4. Version of Record published: January 7, 2019 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Elisabeth R Knoll
  2. Z Iris Zhu
  3. Debasish Sarkar
  4. David Landsman
  5. Randall H Morse
(2018)
Role of the pre-initiation complex in Mediator recruitment and dynamics
eLife 7:e39633.
https://doi.org/10.7554/eLife.39633

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