Scientists have longed to use “The Force” – provided by intracellular entities known as midichlorians – to help around the lab; now, an epigenetic alliance reports that an intracellular fibroblast component – Histone H1.0 – uses The Force and orchestrates cell mechanics when facing Sith-like evils such as physical/chemical stressors. The force is strong with histone H1.0!
Jedi-like researchers led by Thomas M. Vondriska (University of California) applied epigenetic “mind tricks” to understand that altered extracellular forces impacted nuclear flexibility and chromatin compaction in fibroblasts, chromatin compaction affected mechanical stability and fibroblast activation,and that stress-induced fibroblast activation prompted cytoskeletal/extracellular matrix-associated gene expression through an epigenetic mechanism. To reveal how communication between extracellular stress and chromatin structure regulates cell mechanics, a Force-ful study into the participation of histone H1.0 (which promotes chromatin folding) in fibroblast responses to stress describes a role for linker histones in orchestrating cell mechanics by coupling force generation, nuclear organization, and gene transcription.
Let’s hear more from Hu and colleagues on how The Force is strong with histone H1.0 when fibroblasts face stress:
- Fibroblasts require tuned histone H1.0 levels and chromatin compaction to respond to cell stress
- Chromatin regulation by histone H1.0 affects cell mechanical behaviors, including contractile force generation, cytoskeletal regulation, motility, and extracellular matrix deposition
- Increasing histone H1.0 levels recapitulates chromatin organization, gene expression, and mechanical cell behaviors in the absence of altered cellular tension or stress
- Decreasing histone H1.0 levels prevents stress-induced fibroblast contraction, proliferation, and migration by reducing chromatin condensation and inducing the expression of cytoskeleton-, force generation-, extracellular matrix-, and cellular motility-associated genes
- Histone H1.0 may work directly by changing nuclear stiffness (which then impacts cell stiffness) in parallel with the effects of histone H1.0 in controlling the transcription of genes associated with altering cellular rigidity
- Histone H1.0 levels influence the global and gene-specific, stress-induced deposition of H3K27 acetylation
- Histone H1.0 depletion blocks stress-induced H3K27 acetylation alterations at fibrosis-associated genes
- Depletion of histone H1.0 in vivo prevents pathologic fibroblast activation (fibrosis – the excess deposition of extracellular matrix proteins and tissue stiffening) in cardiac muscle via a reduction in histone H1.0 chromatin binding and fiber compaction
These findings reveal that The Force is strong with histone H1.0, which regulates fibroblast stress responses by coupling chromatin organization with cell mechanics. Furthermore, these data support a model in which the perturbation of normal chromatin architecture regulates the cellular response to stress through this all-important linker histone.
For more on how histone H1.0 uses The Force to respond to stress, see Nature Cardiovascular Research, April 2024.