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H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis

By Andrey Poleshko, Cheryl L Smith, Son C. Nguyen, Priya Sivaramakrishnan, John Isaac Murray, Melike Lakadamyali, Eric F. Joyce, Rajan Jain, Jonathan A Epstein

Posted 21 Jun 2019
bioRxiv DOI: 10.1101/678987

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. Here we show that histone 3 lysine 9 dimethylation (H3K9me2) specifically marks peripheral heterochromatin and is retained through mitosis when phosphorylation of histone 3 serine 10 shields the H3K9me2 mark allowing for dissociation from the nuclear lamina. 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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