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


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
    (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
    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


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)


© 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.


  • 8,538
    Page views
  • 1,438
  • 108

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Hamish W King
  2. Robert J Klose
The pioneer factor OCT4 requires BRG1 to functionally mature gene regulatory elements in mouse embryonic stem cells
eLife 6:e22631.
  1. Further reading

Further reading

    1. Cell Biology
    2. Stem Cells and Regenerative Medicine
    Huachao Huang, Yinshan Fang ... Jianwen Que
    Research Article

    Viral infection often causes severe damage to the lungs, leading to the appearance of ectopic basal cells (EBCs) and tuft cells in the lung parenchyma. Thus far the roles of these ectopic epithelial cells in alveolar regeneration remain controversial. Here, we confirm that the ectopic tuft cells are originated from EBCs in mouse models and COVID-19 lungs. The differentiation of tuft cells from EBCs is promoted by Wnt inhibition while suppressed by Notch inhibition. Although progenitor functions have been suggested in other organs, pulmonary tuft cells don't proliferate or give rise to other cell lineages. Consistent with previous reports, Trp63CreERT2 and KRT5-CreERT2 labeled ectopic EBCs do not exhibit alveolar regeneration potential. Intriguingly, when tamoxifen was administrated post viral infection, Trp63CreERT2 but not KRT5-CreERT2 labels islands of alveolar epithelial cells that are negative for EBC biomarkers. Furthermore, germline deletion of Trpm5 significantly increases the contribution of Trp63CreERT2 labeled cells to the alveolar epithelium. Although Trpm5 is known to regulate tuft cell development, complete ablation of tuft cell production fails to improve alveolar regeneration in Pou2f3-/- mice, implying that Trpm5 promotes alveolar epithelial regeneration through a mechanism independent of tuft cells.

    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine
    Xin Li, Noor Singh ... Kacy Lynn Gordon
    Research Advance

    The Caenorhabditis elegans adult hermaphrodite germline is surrounded by a thin tube formed by somatic sheath cells that support germ cells as they mature from the stem-like mitotic state through meiosis, gametogenesis, and ovulation. Recently, we discovered that the distal Sh1 sheath cells associate with mitotic germ cells as they exit the niche Gordon et al., 2020. Here, we report that these sheath-associated germ cells differentiate first in animals with temperature-sensitive mutations affecting germ cell state, and stem-like germ cells are maintained distal to the Sh1 boundary. We analyze several markers of the distal sheath, which is best visualized with endogenously tagged membrane proteins, as overexpressed fluorescent proteins fail to localize to distal membrane processes and can cause gonad morphology defects. However, such reagents with highly variable expression can be used to determine the relative positions of the two Sh1 cells, one of which often extends further distal than the other.