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H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis.

Andrey Poleshko | Cheryl L Smith | Son C Nguyen | Priya Sivaramakrishnan | Karen G Wong | John Isaac Murray | Melike Lakadamyali | Eric F Joyce | Rajan Jain | Jonathan A Epstein
eLife | 2019

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.

Pubmed ID: 31573510

Antibodies used in this publication

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM128903
  • Agency: Burroughs Wellcome Fund, International
    Id: Career Award for Medical Scientists
  • Agency: NIH HHS, United States
    Id: DP2-HL147123
  • Agency: National Science Foundation, International
    Id: CMMI-1548571
  • Agency: Gilead Sciences, International
    Id: Gilead Research Scholars Program
  • Agency: NHLBI NIH HHS, United States
    Id: DP2 HL147123
  • Agency: NIH HHS, United States
    Id: R35 HL140018
  • Agency: NHLBI NIH HHS, United States
    Id: R35 HL140018
  • Agency: NIH HHS, United States
    Id: R35 GM127093
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM127093

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MATLAB (tool)

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