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Updated: Jan 25, 2026

Enhancing Tumor Content through Tumor Macrodissection
Published on: February 12, 2022
Tumor suppressor SMARCB1 suppresses super-enhancers to govern hESC lineage determination
Lee F Langer1,2, James M Ward1,3, Trevor K Archer1
1Laboratory of Epigenetics and Stem Cell Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, United States.
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.
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