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Cited by 44Genomics and Chromatin DynamicsNuclear Structure and FunctionChromatin Remodeling and Cancer

The nuclear periphery is a scaffold for tissue-specific enhancers

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Smith, Cheryl L, Poleshko, Andrey, Epstein, Jonathan A·2021·Nucleic Acids Research
DOI 10.1093/nar/gkab392PMC PMC8216274
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Abstract

Nuclear architecture influences gene regulation and cell identity by controlling the three-dimensional organization of genes and their distal regulatory sequences, which may be far apart in linear space. The genome is functionally and spatially segregated in the eukaryotic nucleus with transcriptionally active regions in the nuclear interior separated from repressive regions, including those at the nuclear periphery. Here, we describe the identification of a novel type of nuclear peripheral chromatin domain that is enriched for tissue-specific transcriptional enhancers. Like other chromatin at the nuclear periphery, these regions are marked by H3K9me2. But unlike the nuclear peripheral Lamina-Associated Domains (LADs), these novel, enhancer-rich domains have limited Lamin B interaction. We therefore refer to them as H3K9me2-Only Domains (KODs). In mouse embryonic stem cells, KODs are found in Hi-C-defined A compartments and feature relatively accessible chromatin. KODs are characterized by low gene expression and enhancers located in these domains bear the histone marks of an inactive or poised state. These results indicate that KODs organize a subset of inactive, tissue-specific enhancers at the nuclear periphery. We hypothesize that KODs may play a role in facilitating and perhaps constraining the enhancer-promoter interactions underlying spatiotemporal regulation of gene expression programs in differentiation and development.

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  • Some A compartment regions consisting of H3K9me2-marked chromatin localise at the nuclear periphery.

    “some A compartment regions consisting of H3K9me2-marked chromatin were also found to localise at the nuclear periphery [464].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [464]

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Cited by

Sorted by citations

Authors
Smith, C. L., Poleshko, A., & Epstein, J. A.
Affiliations
University of Pennsylvania (US)
Corresponding author
Epstein, Jonathan A
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2021-05-22
Volume
49
Issue
11
Pages
6181-6195
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkab392
PMC
PMC8216274
OpenAlex
W3165276636
Cited by
44
References
8
Citations by year
2026: 4 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 15 · 2021: 3
FWCI
2.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (R35 HL140018)
  • Cotswold Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
nuclear periphery, tissue-specific enhancers, lamin B, H3K9me2, chromatin accessibility, enhancer-promoter interactions, mouse embryonic stem cells, nuclear organization, 3D genome organization
MeSH terms
Animals, Cell Line, Cell Nucleus, Chromatin, Enhancer Elements, Genetic, Histones, Organ Specificity, Transcription, Genetic, Lamin Type B, Histone Code, Mice, Embryonic Stem Cells

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