1. Chromosomes and Gene Expression
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Tumor suppressor SMARCB1 suppresses super-enhancers to govern hESC lineage determination

  1. Lee F Langer
  2. James M Ward
  3. Trevor K Archer  Is a corresponding author
  1. National Institute of Environmental Health Sciences, National Institutes of Health, United States
Research Article
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Cite this article as: eLife 2019;8:e45672 doi: 10.7554/eLife.45672

Abstract

The SWI/SNF complex is a critical regulator of pluripotency in human embryonic stem cells (hESCs), and individual subunits have varied and specific roles during development and in diseases. The core subunit SMARCB1 is required for early embryonic survival, and mutations can give rise to atypical teratoid/rhabdoid tumors (AT/RTs) in the pediatric central nervous system. We report that in contrast to other studied systems, SMARCB1 represses bivalent genes in hESCs and antagonizes chromatin accessibility at super-enhancers. Moreover, and consistent with its established role as a CNS tumor suppressor, we find that SMARCB1 is essential for neural induction but dispensable for mesodermal or endodermal differentiation. Mechanistically, we demonstrate that SMARCB1 is essential for hESC super-enhancer silencing in neural differentiation conditions. This genomic assessment of hESC chromatin regulation by SMARCB1 reveals a novel positive regulatory function at super-enhancers and a unique lineage-specific role in regulating hESC differentiation.

Article and author information

Author details

  1. Lee F Langer

    Laboratory of Epigenetics and Stem Cell Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. James M Ward

    Laboratory of Epigenetics and Stem Cell Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Trevor K Archer

    Laboratory of Epigenetics and Stem Cell Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, United States
    For correspondence
    archer1@niehs.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7651-3644

Funding

National Institute of Environmental Health Sciences (Z01 ES071006-18)

  • Trevor K Archer

National Institute of General Medical Sciences (GM120018)

  • Lee F Langer

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

Reviewing Editor

  1. Michael R Green, Howard Hughes Medical Institute, University of Massachusetts Medical School, United States

Publication history

  1. Received: January 31, 2019
  2. Accepted: April 29, 2019
  3. Accepted Manuscript published: April 29, 2019 (version 1)

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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