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Cited by 270Genomics and Chromatin DynamicsPluripotent Stem Cells ResearchChromatin Remodeling and Cancer

The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells

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King, Hamish W, Klose, Robert J·2017·eLife
DOI 10.7554/elife.22631PMC PMC5400504
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Abstract

Pioneer transcription factors recognise and bind their target sequences in inaccessible chromatin to establish new transcriptional networks throughout development and cellular reprogramming. During this process, pioneer factors establish an accessible chromatin state to facilitate additional transcription factor binding, yet it remains unclear how different pioneer factors achieve this. 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 to support additional 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 promoting the activity of the pioneer factor OCT4 and regulating the pluripotency network.

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  • Pioneer factors have been shown to be dependent on chromatin remodelers during differentiation.

    “Moreover, pioneer factors have been shown to be dependent on chromatin remodelers during differentiation60.”

    From Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading (2017) · cites this paper as [60]

    The Discussion (page not available) states that OCT4 requires the chromatin remodeller BRG1 for chromatin accessibility and notes a similar dependency for GATA3. However, the direct experiments concern mouse embryonic stem cells; the Results section on reprogramming and development says only that developmental transitions may require OCT4 and BRG1. The source therefore does not establish a general dependency of pioneer factors on remodelers during differentiation. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Many pioneer factors recruit chromatin remodelers.

    “The mechanisms of pioneer factor action are still being established [37], but at least some of them (such as FOXA, OCT4 and SOX2/SOX11) have been shown to initiate chromatin opening by direct displacement of histones [38–41], whilst many others recruit chromatin remodelers [42–50].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [45]

    The Discussion (page unavailable) reports that OCT4 recruits BRG1 to its binding sites and suggests that many pioneer factors may rely on chromatin remodelling. It does not establish that many other pioneer factors recruit remodelers; it presents that broader mechanism as a possibility requiring further study. (LLM, conf=0.83)

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Authors
King, H. W., & Klose, R. J.
Affiliations
University of Oxford (GB)
Corresponding author
Klose, Robert J
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2017-03-13
Volume
6
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.22631
PMC
PMC5400504
OpenAlex
W2595380755
Cited by
270
References
86
Citations by year
2026: 27 · 2025: 24 · 2024: 32 · 2023: 38 · 2022: 34 · 2021: 34 · 2020: 25 · 2019: 26 · 2018: 28 · 2017: 2
FWCI
9.05
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
Funders
  • Wellcome (098024/Z/11/Z)
  • European Research Council (681440)
  • University of Oxford (Exeter College, University of Oxford, Monsanto Senior Research Fellowship)
  • Lister Institute of Preventive Medicine
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
Oct4, SMARCA4, pioneer transcription factors, chromatin accessibility, chromatin remodeling, mouse embryonic stem cells, pluripotency, gene regulatory elements, cellular reprogramming, early mouse development
MeSH terms
Animals, Cell Differentiation, Chromatin, DNA, DNA Helicases, Gene Expression Regulation, Nuclear Proteins, Protein Binding, Transcription Factors, Octamer Transcription Factor-3, Mice, Embryonic Stem Cells

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