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bioRxiv · 10.1101/455600

The Nucleus Mediates Mechanosensitive Reorganization of Epigenetically Marked Chromatin During Cardiac Maturation and Pathology

Seelbinder, B.·Ghosh, S.·Berman, A. G.·Schneider, S. E.·Goergen, C. J.·Calve, S.·Neu, C. P.
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Abstract

Environmental mechanical cues are critical to guide cell fate. Forces transmit to the nucleus through the Linker of Nucleo- and Cytoskeleton (LINC) complex and are thought to influence the organization of chromatin that is related to cell differentiation; however, the underlying mechanisms are unclear. Here, we investigated chromatin reorganization during murine cardiac development and found that cardiomyocytes establish a distinct architecture characterized by relocation of H3K9me3-modified chromatin from the nuclear interior to the periphery and co-localization to myofibrils. This effect was abrogated in stiff environments that inhibited cardiomyocyte contractility, or after LINC complex disruption, and resulted in the relocation of H3K27me3-modified chromatin instead. By generating high-resolution intra-nuclear strain maps during cardiomyocyte contraction, we discovered that the reorganization of H3K9me3-marked chromatin is influenced by tensile, but not compressive, nuclear strains. Our findings highlight a new role for nuclear mechanosensation in guiding cell fate through chromatin reorganization in response to environmental cues.

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Seelbinder, B., Ghosh, S., Berman, A. G., Schneider, S. E., Goergen, C. J., Calve, S., Neu, C. P.. 2018-10-29. The Nucleus Mediates Mechanosensitive Reorganization of Epigenetically Marked Chromatin During Cardiac Maturation and Pathology. https://doi.org/10.1101/455600

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