1. Cell Biology
  2. Chromosomes and Gene Expression

H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis

  1. Andrey Poleshko
  2. Cheryl L Smith
  3. Son C Nguyen
  4. Priya Sivaramakrishnan
  5. Karen G Wong
  6. John Isaac Murray
  7. Melike Lakadamyali
  8. Eric F Joyce
  9. Raj Jain  Is a corresponding author
  10. Jonathan A Epstein  Is a corresponding author
  1. University of Pennsylvania, United States
https://doi.org/10.7554/eLife.49278
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  1. Andrey Poleshko
  2. Cheryl L Smith
  3. Son C Nguyen
  4. Priya Sivaramakrishnan
  5. Karen G Wong
  6. John Isaac Murray
  7. Melike Lakadamyali
  8. Eric F Joyce
  9. Raj Jain
  10. Jonathan A Epstein
(2019)
H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis
eLife 8:e49278.
https://doi.org/10.7554/eLife.49278
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Abstract

Cell-type-specific 3D organization of the genome is unrecognizable during mitosis. It remains unclear how essential positional information is transmitted through cell division such that a daughter cell recapitulates the spatial genome organization of the parent. Lamina-associated domains (LADs) are regions of repressive heterochromatin positioned at the nuclear periphery that vary by cell type and contribute to cell-specific gene expression and identity. Here we show that histone 3 lysine 9 dimethylation (H3K9me2) is an evolutionarily conserved, specific mark of nuclear peripheral heterochromatin and that it is retained through mitosis. During mitosis, phosphorylation of histone 3 serine 10 temporarily shields the H3K9me2 mark allowing for dissociation of chromatin from the nuclear lamina. Using high-resolution 3D immuno-oligoFISH, we demonstrate that H3K9me2-enriched genomic regions, which are positioned at the nuclear lamina in interphase cells prior to mitosis, re-associate with the forming nuclear lamina before mitotic exit. The H3K9me2 modification of peripheral heterochromatin ensures that positional information is safeguarded through cell division such that individual LADs are re-established at the nuclear periphery in daughter nuclei. Thus, H3K9me2 acts as a 3D architectural mitotic guidepost. Our data establish a mechanism for epigenetic memory and inheritance of spatial organization of the genome.

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All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Andrey Poleshko

    Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Cheryl L Smith

    Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Son C Nguyen

    Department of Genetics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Priya Sivaramakrishnan

    Department of Genetics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8717-8287

  5. Karen G Wong

    Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. John Isaac Murray

    Department of Genetics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4026-584X

  7. Melike Lakadamyali

    Department of Physiology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Eric F Joyce

    Department of Genetics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0418-2804

  9. Raj Jain

    Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, United States
    For correspondence
    jainr@pennmedicine.upenn.edu
    Competing interests
    The authors declare that no competing interests exist.

  10. Jonathan A Epstein

    Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, United States
    For correspondence
    epsteinj@pennmedicine.upenn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8637-4465

Funding

National Institutes of Health (R35 HL140018)

  • Jonathan A Epstein

National Institutes of Health (DP2-HL147123)

  • Raj Jain

National Institutes of Health (R35 GM127093)

  • John Isaac Murray

Cotswold Foundation

  • Jonathan A Epstein

WW Smith Endowed Chair

  • Jonathan A Epstein

Burroughs Welcome Career Award for Medical Scientists and the Gilead Research Scholars Program

  • Raj Jain

National Science Foundation (CMMI-1548571)

  • Raj Jain
  • Jonathan A Epstein

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

Copyright

© 2019, Poleshko et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Andrey Poleshko
  2. Cheryl L Smith
  3. Son C Nguyen
  4. Priya Sivaramakrishnan
  5. Karen G Wong
  6. John Isaac Murray
  7. Melike Lakadamyali
  8. Eric F Joyce
  9. Raj Jain
  10. Jonathan A Epstein
(2019)
H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis
eLife 8:e49278.
https://doi.org/10.7554/eLife.49278

Share this article

https://doi.org/10.7554/eLife.49278

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