RT Journal Article
SR Electronic
T1 Intra-Nuclear Tensile Strain Mediates Reorganization of Epigenetically Marked Chromatin During Cardiac Development and Disease
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 455600
DO 10.1101/455600
A1 Benjamin Seelbinder
A1 Soham Ghosh
A1 Alycia G. Berman
A1 Stephanie E. Schneider
A1 Craig J. Goergen
A1 Sarah Calve
A1 Corey P. Neu
YR 2019
UL http://biorxiv.org/content/early/2019/08/11/455600.abstract
AB 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.