Intra-Nuclear Tensile Strain Mediates Reorganization of Epigenetically Marked Chromatin During Cardiac Development and Disease
Seelbinder, B.; Ghosh, S.; Berman, A. G.; Schneider, S. E.; Goergen, C. J.; Calve, S.; Neu, C. P.
Show 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.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Identification of epigenetic regulators of fibrotic transformation in cardiac fibroblasts through bulk and single-cell CRISPR screens 97%
- The pericardium forms as a distinct structure during heart formation 96%
- Reproducing extracellular matrix adverse remodelling of non-ST myocardialinfarction in a large animal model 96%
Similar papers in this journal
- A disrupted compartment boundary underlies abnormal cardiac patterning and congenital heart defects 97%
- An engineered human cardiac tissue model reveals contributions of systemic lupus erythematosus autoantibodies to myocardial injury 96%
- Targeted glycophagy ATG8 therapy reverses diabetic heart disease in mice and in human engineered cardiac tissues 96%
Similar papers in this journal
- A biomechanical switch regulates the transition towards homeostasis in esophageal epithelium 96%
- Mechano-osmotic signals control chromatin state and fate transitions in pluripotent stem cells 95%
- Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.