1. Stem Cells and Regenerative Medicine
  2. Chromosomes and Gene Expression
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The pioneer factor OCT4 requires BRG1 to functionally mature gene regulatory elements in mouse embryonic stem cells

  1. Hamish W King
  2. Robert J Klose  Is a corresponding author
  1. University of Oxford, United Kingdom
Research Article
  • Cited 82
  • Views 7,280
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Cite this article as: eLife 2017;6:e22631 doi: 10.7554/eLife.22631

Abstract

Pioneer transcription factors recognise and bind their target sequences in inaccessible chromatin to establish new transcriptional networks during development and cellular reprogramming. During this process, pioneer factors establish an accessible chromatin state to facilitate additional transcription factor binding, yet how different pioneer factors achieve this remains unclear. Here, we discover that the pluripotency-associated pioneer factor OCT4 binds chromatin to shape accessibility, transcription factor co-binding, and regulatory element function in mouse embryonic stem cells. Chromatin accessibility at OCT4-bound sites requires the chromatin remodeller BRG1, which is recruited to these sites by OCT4. BRG1 occupancy supports transcription factor binding and expression of the pluripotency-associated transcriptome. Furthermore, the requirement for BRG1 in shaping OCT4 binding reflects how these target sites are used during cellular reprogramming and early mouse development. Together this reveals a distinct requirement for a chromatin remodeller in shaping the activity of the pioneer factor OCT4 and regulating the pluripotency network.

Data availability

The following data sets were generated
The following previously published data sets were used
    1. ENCODE DCC
    (2014) A comparative encyclopedia of DNA elements in the mouse genome
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE49847).

Article and author information

Author details

  1. Hamish W King

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5972-8926
  2. Robert J Klose

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    For correspondence
    rob.klose@bioch.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8726-7888

Funding

Wellcome (098024/Z/11/Z)

  • Robert J Klose

European Research Council (681440)

  • Robert J Klose

Exeter College, University of Oxford (Monsanto Senior Research Fellowship)

  • Robert J Klose

Lister Institute of Preventive Medicine

  • Robert J Klose

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

Reviewing Editor

  1. Irwin Davidson, Institut de Génétique et de Biologie Moléculaire et Cellulaire, France

Publication history

  1. Received: October 26, 2016
  2. Accepted: March 9, 2017
  3. Accepted Manuscript published: March 13, 2017 (version 1)
  4. Accepted Manuscript updated: March 15, 2017 (version 2)
  5. Version of Record published: April 21, 2017 (version 3)

Copyright

© 2017, King & Klose

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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