TitleInitiation of wound healing is regulated by the convergence of mechanical and epigenetic cues.
Publication TypeJournal Article
Year of Publication2022
AuthorsBhatt T, Dey R, Hegde A, Ketkar AAshok, Pulianmackal AJ, Deb AP, Rampalli S, Jamora C
JournalPLoS Biol
Volume20
Issue9
Paginatione3001777
Date Published2022 09
ISSN1545-7885
KeywordsBiomarkers, Caspase 8, Cues, Epigenesis, Genetic, Wound Healing
Abstract

Wound healing in the skin is a complex physiological process that is a product of a cell state transition from homeostasis to repair. Mechanical cues are increasingly being recognized as important regulators of cellular reprogramming, but the mechanism by which it is translated to changes in gene expression and ultimately cellular behavior remains largely a mystery. To probe the molecular underpinnings of this phenomenon further, we used the down-regulation of caspase-8 as a biomarker of a cell entering the wound healing program. We found that the wound-induced release of tension within the epidermis leads to the alteration of gene expression via the nuclear translocation of the DNA methyltransferase 3A (DNMT3a). This enzyme then methylates promoters of genes that are known to be down-regulated in response to wound stimuli as well as potentially novel players in the repair program. Overall, these findings illuminate the convergence of mechanical and epigenetic signaling modules that are important regulators of the transcriptome landscape required to initiate the tissue repair process in the differentiated layers of the epidermis.

DOI10.1371/journal.pbio.3001777
Alternate JournalPLoS Biol
PubMed ID36112666
PubMed Central IDPMC9522318

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