Histone H1.0 couples cellular mechanical behaviors to chromatin structure.

Autor: Hu S; Department of Anesthesiology & Perioperative Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA USA., Chapski DJ; Department of Anesthesiology & Perioperative Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA USA., Gehred ND; Department of Anesthesiology & Perioperative Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA USA., Kimball TH; Department of Anesthesiology & Perioperative Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA USA., Gromova T; Department of Anesthesiology & Perioperative Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA USA., Flores A; Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA USA., Rowat AC; Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA USA., Chen J; Department of Medicine, Division of Cardiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA USA., Packard RRS; Department of Medicine, Division of Cardiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA USA.; Department of Physiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA USA., Olszewski E; Department of Bioengineering, University of Washington, Seattle, WA USA., Davis J; Department of Bioengineering, University of Washington, Seattle, WA USA., Rau CD; Department of Genetics and McAllister Heart Institute, University of North Carolina, Chapel Hill, NC USA., McKinsey TA; Department of Medicine, Division of Cardiology and Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, CO USA., Rosa-Garrido M; Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL USA., Vondriska TM; Department of Anesthesiology & Perioperative Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA USA.; Department of Medicine, Division of Cardiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA USA.; Department of Physiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA USA.
Jazyk: angličtina
Zdroj: Nature cardiovascular research [Nat Cardiovasc Res] 2024; Vol. 3 (4), pp. 441-459. Date of Electronic Publication: 2024 Apr 10.
DOI: 10.1038/s44161-024-00460-w
Abstrakt: Tuning of genome structure and function is accomplished by chromatin-binding proteins, which determine the transcriptome and phenotype of the cell. Here we investigate how communication between extracellular stress and chromatin structure may regulate cellular mechanical behaviors. We demonstrate that histone H1.0, which compacts nucleosomes into higher-order chromatin fibers, controls genome organization and cellular stress response. We show that histone H1.0 has privileged expression in fibroblasts across tissue types and that its expression is necessary and sufficient to induce myofibroblast activation. Depletion of histone H1.0 prevents cytokine-induced fibroblast contraction, proliferation and migration via inhibition of a transcriptome comprising extracellular matrix, cytoskeletal and contractile genes, through a process that involves locus-specific H3K27 acetylation. Transient depletion of histone H1.0 in vivo prevents fibrosis in cardiac muscle. These findings identify an unexpected role of linker histones to orchestrate cellular mechanical behaviors, directly coupling force generation, nuclear organization and gene transcription.
Competing Interests: Competing interestsThe authors declare no competing interests.
(© The Author(s) 2024.)
Databáze: MEDLINE
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