- •Transcriptional reprogramming upon stress signaling is mediated by chromatin dynamics regulated by epigenetics.
- •An epigenetic regulator, Mi-2β, plays a leading role in skin stress adaptation by organizing chromatin environment.
- •Stress signaling override the repressive activity of Mi-2β, thereby allowing skin repair to occur.
- •The emerging role of epigentic regulators in stress adaptation open new avenues for understanding human skin health and disease development.
The skin, which is constantly exposed to a wide variety of environmental insults, maintains its integrity by rapidly responding to external signals. In the epidermis, most genes are set in transcriptionally poised conditions to prepare for the prompt induction of stress responding genes. Local chromatin dynamics, supported by an interplay between epigenetic regulators and transcription factors, underlies transcriptional responses upon stress exposure. This review summarizes the epigenetic mechanism regulating gene expression and discusses how stress signaling provokes chromatin reprogramming in the epidermis. Epigenetic regulators play a leading role in chromatin remodeling during stress adaptation, and the timely release and restoration of these factors are indispensable for an appropriate skin repair. Evidence for the epigenetic regulation of physiological responses in the skin is accumulating. The epigenetic environment under continuous stress stimuli may lead to the acquisition of stress tolerance, but at the same time, may also induce pathological hypersensitivity. This review describes the current understanding of epigenetics and provides the potential of epigenetic regulation in skin disease development.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Journal of Dermatological Science
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Psoriasis: more than skin deep.Nat. Med. 2005; 11: 17-18
- Skin immune sentinels in health and disease.Nat. Rev. Immunol. 2009; 9: 679-691
- The epithelial immune microenvironment (EIME) in atopic dermatitis and psoriasis.Nat. Immunol. 2018; 19: 1286-1298
- Stretching the limits: from homeostasis to stem cell plasticity in wound healing and cancer.Nat. Rev. Genet. 2018; 19: 311-325
- Tissue-resident memory T cells.Immunity. 2014; 41: 886-897
- Tissue stem cells: architects of their niches.Cell Stem Cell. 2020; 27: 532-556
- Haematopoietic cell-fate decisions, chromatin regulation and ikaros.Nat. Rev. Immunol. 2002; 2: 162-174
- Chromatin dynamics during cellular reprogramming.Nature. 2013; 502: 462-471
- Histone variants on the move: substrates for chromatin dynamics.Nat. Rev. Mol. Cell Biol. 2017; 18: 115-126
- Stem cell lineage infidelity drives wound repair and cancer.Cell. 2017; 169 (636-650 e614)
- Inflammatory memory sensitizes skin epithelial stem cells to tissue damage.Nature. 2017; 550: 475-480
- Lineage-specific dynamic and pre-established enhancer-promoter contacts cooperate in terminal differentiation.Nat. Genet. 2017; 49: 1522-1528
- Harnessing of the nucleosome-remodeling-deacetylase complex controls lymphocyte development and prevents leukemogenesis.Nat. Immunol. 2011; 13: 86-94
- Chromatin history: our view from the bridge.Nat. Rev. Mol. Cell Biol. 2003; 4: 809-814
- The role of chromatin during transcription.Cell. 2007; 128: 707-719
- DNA methylation and histone modifications: teaming up to silence genes.Curr. Opin. Genet. Dev. 2005; 15: 490-495
- Reevaluating the roles of histone-modifying enzymes and their associated chromatin modifications in transcriptional regulation.Nat. Genet. 2020; 52: 1271-1281
- Histone methylation has dynamics distinct from those of histone acetylation in cell cycle reentry from quiescence.Mol. Cell. Biol. 2014; 34: 3968-3980
- Dynamic remodeling of histone modifications in response to osmotic stress in Saccharomyces cerevisiae.BMC Genomics. 2014; 15: 247
- Histone modifying enzymes: structures, mechanisms, and specificities.Biochim. Biophys. Acta. 2009; 1789: 58-68
- Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex.Nature. 1998; 395: 917-921
- A molecular dissection of the repression circuitry of Ikaros.J. Biol. Chem. 2002; 277: 27697-27705
- Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy.Nat. Genet. 2013; 45: 592-601
- The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities.Cell. 1998; 95: 279-289
- The nucleosome remodeling and deacetylase complex in development and disease.Transl. Res. 2015; 165: 36-47
- ISWI chromatin remodeling: one primary actor or a coordinated effort?.Curr. Opin. Struct. Biol. 2014; 24: 150-155
- Structure and subunit topology of the INO80 chromatin remodeler and its nucleosome complex.Cell. 2013; 154: 1207-1219
- The chromatin remodeler Mi-2beta is required for CD4 expression and T cell development.Immunity. 2004; 20: 719-733
- Chromatin dynamics: interplay between remodeling enzymes and histone modifications.Biochim. Biophys. Acta. 2014; 1839: 728-736
- Hdac1 and Hdac2 act redundantly to control p63 and p53 functions in epidermal progenitor cells.Dev. Cell. 2010; 19: 807-818
- p63 identifies keratinocyte stem cells.Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 3156-3161
- The histone methyltransferase Setd8 acts in concert with c-Myc and is required to maintain skin.EMBO J. 2012; 31: 616-629
- A novel ATAC-seq approach reveals lineage-specific reinforcement of the open chromatin landscape via cooperation between BAF and p63.Genome Biol. 2015; 16: 284
- The chromatin remodeler Mi-2beta is required for establishment of the basal epidermis and normal differentiation of its progeny.Development. 2007; 134: 1571-1582
- Functional interactions between Mi-2beta and AP1 complexes control response and recovery from skin barrier disruption.J. Exp. Med. 2020; 217
- Analysis of chromatin accessibility in human epidermis identifies putative barrier dysfunction-sensing enhancers.PLoS One. 2017; 12e0184500
- Oxidative stress signaling to chromatin in health and disease.Epigenomics. 2016; 8: 843-862
- Epigenetic switch from repressive to permissive chromatin in response to cold stress.Proc. Natl. Acad. Sci. U. S. A. 2018; 115: E5400-E5409
- Direct control of regulatory T cells by keratinocytes.Nat. Immunol. 2017; 18: 334-343
- Differential expression of the fos and jun family members c-fos, fosB, Fra-1, Fra-2, c-jun, junB and junD during human epidermal keratinocyte differentiation.Oncogene. 1995; 11: 2681-2687
- c-Jun is essential for organization of the epidermal leading edge.Dev. Cell. 2003; 4: 865-877
- JunB defines functional and structural integrity of the epidermo-pilosebaceous unit in the skin.Nat. Commun. 2018; 9: 3425
- EZH1 and EZH2 cogovern histone H3K27 trimethylation and are essential for hair follicle homeostasis and wound repair.Genes Dev. 2011; 25: 485-498
- Histone H3K27 demethylase JMJD3 in cooperation with NF-kappaB regulates keratinocyte wound healing.J. Invest. Dermatol. 2016; 136: 847-858
- The CDK4/6-EZH2 pathway is a potential therapeutic target for psoriasis.J. Clin. Invest. 2020; 130: 5765-5781
- Epigenetic reprogramming during wound healing: loss of polycomb-mediated silencing may enable upregulation of repair genes.EMBO Rep. 2009; 10: 881-886
- A nitric oxide-dependent cross-talk between class I and III histone deacetylases accelerates skin repair.J. Biol. Chem. 2013; 288: 11004-11012
- Cutaneous innate immune tolerance is mediated by epigenetic control of MAP2K3 by HDAC8/9.Sci. Immunol. 2021; 6
- Trained immunity: a tool for reducing susceptibility to and the severity of SARS-CoV-2 infection.Cell. 2020; 181: 969-977
- Distribution and storage of inflammatory memory in barrier tissues.Nat. Rev. Immunol. 2020; 20: 308-320
Sayaka Shibata received her M.D. in 2004 from the University of Tokyo, and Ph.D. in 2011 from Graduate School of Medicine and Faculty of Medicine, The University of Tokyo. She worked as a postdoctoral at the Katia Georgopoulos Laboratory in the Cutaneous Biology Research Center at Massachusetts General Hospital, Harvard Medical School, where she became fascinated by epigenetics. She is now an associate professor at Department of Dermatology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo. Her current research interest is epigenetics in skin inflammatory diseases.
Published online: June 25, 2021
Accepted: June 23, 2021
Received in revised form: June 23, 2021
Received: June 12, 2021
© 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.