H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis
- University of Pennsylvania, United States
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Priya Sivaramakrishnan
Jonathan A Epstein
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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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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