Epigenetic control in skin development, homeostasis and injury repair

Abstract

Cell‐type‐ and cell‐state‐specific patterns of covalent modifications on DNA and histone tails form global epigenetic profiles that enable spatiotemporal regulation of gene expression. These epigenetic profiles arise from coordinated activities of transcription factors and epigenetic modifiers, which result in cell‐type‐specific outputs in response to dynamic environmental conditions and signalling pathways. Recent mouse genetic and functional studies have highlighted the physiological significance of global DNA and histone epigenetic modifications in skin. Importantly, specific epigenetic profiles are emerging for adult skin stem cells that are associated with their cell fate plasticity and proper activity in tissue regeneration. We can now begin to draw a more comprehensive picture of how epigenetic modifiers orchestrate their cell‐intrinsic role with microenvironmental cues for proper skin development, homeostasis and wound repair. The field is ripe to begin to implement these findings from the laboratory into skin therapies.

A review of epigenetic regulation in wound healing: Implications for the future of wound care

“…DNA methylation involves a post‐replication addition of a methyl group to the C5 position of cytosine to form 5‐methylthytocyne, the process of which is co‐ordinated by DNA methyltransferases (DNMTs) 12,13 . This process regulates gene expression by inhibiting transcription factor binding to DNA or by interacting with methyl‐DNA‐binding proteins that target repressive chromatin remodeling complexes to the methylated genomic regions, 12 and is reversible through the activity of 10 to 11 translocation (TET) proteins 13 . There are, however, instances where DNA methylation contributes to gene activation, 14,15 including through blocking of upstream repressor sequences 16 .…”

Understanding skin morphogenesis across developmental, regenerative and evolutionary levels

“…Wound‐induced regeneration is thought to be controlled by a complex signalling and epigenetic mechanism . In this issue, Garza's and Tumbar's groups discuss the roles of non‐coding double‐stranded RNAs and epigenetic reprogramming, respectively, in enabling such regenerative behaviour. The review article by Chuong et al discusses the emerging evidence that in addition to molecular signals, regenerative responses in skin wounds are also profoundly controlled by mechanical cues.…”

“…Powerful insights on morphogenesis can be learned from emerging model organisms, whose skin has distinct anatomical or physiological features. In this issue, several works show how research on African spiny mice, African striped mice, pigs and dogs can advance the understanding of skin morphogenesis and regeneration. Interestingly, the degree to which different mammalian species can activate wound‐induced neogenesis programs can vary substantially.…”

Epigenetic treatment of dermatologic disorders

“…Thus, reshaping the microbiome (Gilbert et al, ) by modifying the genetic diversity of the various commensal bacterial compositions towards a healthier state, especially on skin (Blume‐Peytavi et al, ; Knight et al, ; McCoy et al, ; Rocha & Bagatin, ; Vollmer, West, & Lephart, ), and/or harnessing them to produce bioactive therapeutic products, including those influencing gene expression, present opportunities for therapeutic intervention (Bueso, Lehouritis, & Tangney, ; Dietert & Dietert, ; Eisenstein, ; O'Neill & Gallo, ). Indeed, therapeutic epigenetic regulation—nongenetic influences on gene expression (changes in phenotype that do not involve alterations in the genomic DNA sequence)—loosely defined as environmentally induced biological processes that silence, activate, and/or modulate gene expression pathways is increasingly garnering clinical recognition (Berson, Nativio, Berger, & Bonini, ; Cock, ; Feinberg, ; Jadotte, ; Kang, Chovatiya, & Tumbar, ; Mervis & McGee, ; Yamatsugu, Kawashima, & Kanai, ).…”

“…Indeed, therapeutic epigenetic regulation-nongenetic influences on gene expression (changes in phenotype that do not involve alterations in the genomic DNA sequence)-loosely defined as environmentally induced biological processes that silence, activate, and/or modulate gene expression pathways is increasingly garnering clinical recognition (Berson, Nativio, Berger, & Bonini, 2018;Cock, 2018;Feinberg, 2018;Jadotte, 2019;Kang, Chovatiya, & Tumbar, 2019;Mervis & McGee, 2019;Yamatsugu, Kawashima, & Kanai, 2018).…”