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Cited by 427Chromatin Remodeling and CancerGenomics and Chromatin DynamicsEpigenetics and DNA Methylation

The SWI/SNF chromatin remodelling complex is required for maintenance of lineage specific enhancers

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Alver, Burak H., Kim, Kimberly H., Lu, Ping, Wang, Xiaofeng, Manchester, Haley E., Wang, Weishan, Haswell, Jeffrey R., Park, Peter J. +1 more·2017·Nature Communications
DOI 10.1038/ncomms14648PMC PMC5343482
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Abstract

Genes encoding subunits of SWI/SNF (BAF) chromatin remodelling complexes are collectively altered in over 20% of human malignancies, but the mechanisms by which these complexes alter chromatin to modulate transcription and cell fate are poorly understood. Utilizing mouse embryonic fibroblast and cancer cell line models, here we show via ChIP-seq and biochemical assays that SWI/SNF complexes are preferentially targeted to distal lineage specific enhancers and interact with p300 to modulate histone H3 lysine 27 acetylation. We identify a greater requirement for SWI/SNF at typical enhancers than at most super-enhancers and at enhancers in untranscribed regions than in transcribed regions. Our data further demonstrate that SWI/SNF-dependent distal enhancers are essential for controlling expression of genes linked to developmental processes. Our findings thus establish SWI/SNF complexes as regulators of the enhancer landscape and provide insight into the roles of SWI/SNF in cellular fate control.

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  • SWI/SNF recruits the chromatin activators P300 and CBP, which mediate acetylation of histone H3 lysine 27 through their intrinsic histone acetyltransferase activity.

    “SWI/SNF recruits the chromatin activators P300 and CBP, which mediate the acetylation of histone H3 lysine 27 through their intrinsic histone acetyltransferase (HAT) activity [59–62].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [62]

    The Results section ('SWI/SNF is required for p300 activity at enhancers'; page not provided) says SWI/SNF recruits p300 to enhancer loci and regulates H3K27 acetylation through interaction with this histone acetyltransferase. It does not establish that SWI/SNF also recruits CBP, so the claim's inclusion of CBP is unsupported by the cited Results passages. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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References 49 · Cited by 427

Research works printed but not linked: 37

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Authors
Alver, B. H., Kim, K. H., Lu, P., Wang, X., Manchester, H. E., Wang, W., Haswell, J. R., Park, P. J., & Roberts, C. W. M.
Affiliations
  • Harvard University (US)
  • Boston Children's Hospital (US)
Corresponding author
  • Park, Peter J.
  • Roberts, Charles W. M.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2017-03-06
Volume
8
Issue
1
Pages
14648-14648
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms14648
PMC
PMC5343482
OpenAlex
W2591968025
Cited by
427
References
49
Citations by year
2026: 35 · 2025: 43 · 2024: 65 · 2023: 65 · 2022: 47 · 2021: 61 · 2020: 55 · 2019: 27 · 2018: 20 · 2017: 9
FWCI
12.40
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Rally Foundation
  • Garrett B. Smith Foundation
  • St. Baldrick's Foundation
  • American Lebanese Syrian Associated Charities
  • National Institutes of Health
  • National Cancer Institute (K99CA197640, R01CA172152, R01CA113794)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
SWI/SNF complex, distal enhancers, super-enhancers, P300, histone H3 lysine 27 acetylation, enhancer landscape, developmental gene expression, chromatin regulation
MeSH terms
Acetylation, Animals, Cells, Cultured, Chromatin, Chromosomal Proteins, Non-Histone, Enhancer Elements, Genetic, Histones, Humans, Lysine, Mice, Transgenic, Protein Binding, Transcription Factors, Mice, Knockout, Chromatin Assembly and Disassembly, Cell Line, Tumor

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