TY - JOUR TI - H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis AU - Poleshko, Andrey AU - Smith, Cheryl L AU - Nguyen, Son C AU - Sivaramakrishnan, Priya AU - Wong, Karen G AU - Murray, John Isaac AU - Lakadamyali, Melike AU - Joyce, Eric F AU - Jain, Rajan AU - Epstein, Jonathan A A2 - Aguilera, Andrés A2 - Tyler, Jessica K A2 - Belmont, Andrew S VL - 8 PY - 2019 DA - 2019/10/01 SP - e49278 C1 - eLife 2019;8:e49278 DO - 10.7554/eLife.49278 UR - https://doi.org/10.7554/eLife.49278 AB - 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. KW - nuclear architecture KW - H3K9me2 KW - mitosis KW - genome organization KW - peripheral heterochromatin KW - nuclear lamina JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -