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Cited by 107Genomics and Chromatin DynamicsNuclear Structure and FunctionChromosomal and Genetic Variations

Constrained release of lamina-associated enhancers and genes from the nuclear envelope during T-cell activation facilitates their association in chromosome compartments

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Robson, Michael I., de las Heras, Jose I., Czapiewski, Rafal, Sivakumar, Aishwarya, Kerr, Alastair R.W., Schirmer, Eric C.·2017·Genome Research
DOI 10.1101/gr.212308.116PMC PMC5495065

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Abstract

The 3D organization of the genome changes concomitantly with expression changes during hematopoiesis and immune activation. Studies have focused either on lamina-associated domains (LADs) or on topologically associated domains (TADs), defined by preferential local chromatin interactions, and chromosome compartments, defined as higher-order interactions between TADs sharing functionally similar states. However, few studies have investigated how these affect one another. To address this, we mapped LADs using Lamin B1–DamID during Jurkat T-cell activation, finding significant genome reorganization at the nuclear periphery dominated by release of loci frequently important for T-cell function. To assess how these changes at the nuclear periphery influence wider genome organization, our DamID data sets were contrasted with TADs and compartments. Features of specific repositioning events were then tested by fluorescence in situ hybridization during T-cell activation. First, considerable overlap between TADs and LADs was observed with the TAD repositioning as a unit. Second, A1 and A2 subcompartments are segregated in 3D space through differences in proximity to LADs along chromosomes. Third, genes and a putative enhancer in LADs that were released from the periphery during T-cell activation became preferentially associated with A2 subcompartments and were constrained to the relative proximity of the lamina. Thus, lamina associations influence internal nuclear organization, and changes in LADs during T-cell activation may provide an important additional mode of gene regulation.

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  • Many LADs remain generally invariant across cell types and conditions, while others can move away from the nuclear periphery, for example, upon T cell differentiation.

    “Whilst many LADs remain generally invariant across cell types and conditions, others can move away from the nuclear periphery, for example, upon T cell differentiation [463].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [463]

    The introductory passage describes constitutive LADs as unchanging and facultative LADs as moving to or from the periphery during differentiation. The Results section, “Important T-cell genes are released from the periphery,” reports that 2.5% of the genome shifted from peripheral to interior association in Jurkat T cells, but this was during T-cell activation, not T-cell differentiation. The paper explicitly distinguishes activation from differentiation. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Relocation of LADs away from the nuclear periphery is associated with activation of the respective regulatory elements and their increased proximity.

    “This relocation is associated with the activation of the respective regulatory elements and their increased proximity [463].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [463]

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Cited by

Sorted by citations

Authors
Robson, M. I., de las Heras, J. I., Czapiewski, R., Sivakumar, A., Kerr, A. R. W., & Schirmer, E. C.
Affiliations
Wellcome Centre for Cell Biology (GB)
ORCID
Venue
Genome Research
Publisher
Cold Spring Harbor Laboratory
Published
2017-04-19
Volume
27
Issue
7
Pages
1126-1138
ISSN
  • 1088-9051 (ISSN-L)
  • 1549-5469
DOI
10.1101/gr.212308.116
PMC
PMC5495065
OpenAlex
W2952935229
Cited by
107
References
11
Citations by year
2026: 2 · 2025: 13 · 2024: 10 · 2023: 11 · 2022: 17 · 2021: 13 · 2020: 14 · 2019: 13 · 2018: 11 · 2017: 2 · 2015: 1
Type
posted content
Language
en
Open access
Locations
  • Genome Research (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc)
Funders
  • Wellcome Trust PhD
  • Wellcome Trust (095209, 092076)
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 › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
lamina-associated domains, T cell activation, nuclear lamina, topologically associating domains, 3D genome organization, gene expression regulation, Jurkat cells, nuclear periphery
MeSH terms
Chromosomes, Human, Enhancer Elements, Genetic, Humans, Lymphocyte Activation, Neoplasm Proteins, Nuclear Envelope, T-Lymphocytes, Jurkat Cells, Lamin Type B

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