BET family members Bdf1/2 modulate global transcription initiation and elongation in Saccharomyces cerevisiae

  1. Rafal Donczew  Is a corresponding author
  2. Steven Hahn  Is a corresponding author
  1. Fred Hutchinson Cancer Research Center, United States

Abstract

Human bromodomain-containing BET family members are promising targets for therapy of cancer and immunoinflammatory diseases, but their mechanisms of action and functional redundancies are poorly understood. Bdf1/2, yeast homologues of the human BET factors, were previously proposed to target transcription factor TFIID to acetylated histone H4, analogous to bromodomains that are present within the largest subunit of metazoan TFIID. We investigated the genome-wide roles of Bdf1/2 and found that their important contributions to transcription extend beyond TFIID function, as transcription of many genes is more sensitive to Bdf1/2 than to TFIID depletion. Bdf1/2 co-occupy the majority of yeast promoters and affect preinitiation complex formation through recruitment of TFIID, Mediator and basal transcription factors to chromatin. Surprisingly, we discovered that hypersensitivity of genes to Bdf1/2 depletion results from combined defects in transcription initiation and early elongation, a striking functional similarity to human BET proteins, most notably Brd4. Our results establish Bdf1/2 as critical for yeast transcription and provide important mechanistic insights into the function of BET proteins in all eukaryotes.

Data availability

The datasets generated during this study are available at Gene Expression Omnibus under accession GSE171067.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Rafal Donczew

    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
    For correspondence
    rdonczew@fredhutch.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9729-4153
  2. Steven Hahn

    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
    For correspondence
    shahn@fhcrc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7240-2533

Funding

National Institute of General Medical Sciences (RO1GM053451)

  • Steven Hahn

National Institute of General Medical Sciences (RO1GM075114)

  • Steven Hahn

National Institute of General Medical Sciences (R35GM140823)

  • Steven Hahn

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

Reviewing Editor

  1. Tim Formosa, University of Utah School of Medicine, United States

Version history

  1. Received: April 21, 2021
  2. Accepted: June 16, 2021
  3. Accepted Manuscript published: June 17, 2021 (version 1)
  4. Version of Record published: July 8, 2021 (version 2)

Copyright

© 2021, Donczew & Hahn

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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  1. Rafal Donczew
  2. Steven Hahn
(2021)
BET family members Bdf1/2 modulate global transcription initiation and elongation in Saccharomyces cerevisiae
eLife 10:e69619.
https://doi.org/10.7554/eLife.69619

Share this article

https://doi.org/10.7554/eLife.69619

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