All Roads Go to the Nucleus: Integration of Signaling/Transcription Factor-Mediated and Epigenetic Regulatory Mechanisms in the Control of Skin Development and Regeneration

  • Vladimir A. BotchkarevEmail author
  • Andrey A. Sharov
  • Michael Y. Fessing
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)


Mammalian skin fulfills a large number of functions including protection of the organism against environmental (physical, chemical, biological) stressors, maintenance of body temperature and water balance, transmission of sensory information and psycho-social communications. To efficiently fulfill these complex functions, the skin develops as an organ that is capable of maintaining its structural integrity and shows a high degree of plasticity in response to changing environmental conditions. Skin development results in formation of the epidermis, dermis and cutaneous appendages. During postnatal life, the epithelial components of the skin, including the epidermis and hair follicles, regenerate, a process that involves the activation of dedicated pools of stem cells. After injury, epidermal and hair follicle stem cells contribute to skin regeneration by supplying their progenies to restore the skin epithelium. Skin development and regeneration are controlled by signaling/transcription factor-mediated and epigenetic mechanisms, which operate in concert to regulate gene expression. Signals received from the external environment are transmitted to the cell nucleus, which operates as a command center conferring responsiveness to extrinsic cues into distinct transcriptional outcomes. Here, we review the current state of research illustrating the critical cross-talk between signaling/transcription factor-mediated and epigenetic mechanisms which is required for execution of skin-specific programs of gene activation and silencing during development, regeneration and adaptation to environmental factors. Additional efforts are required to fully understand how the epigenome in cutaneous cells is re-organized during these processes. Future research in this direction will help to bridge the gap between our current knowledge of signaling/transcription factor-mediated and epigenetic mechanisms and potential applications of signaling and epigenetic modulators, which may provide new approaches for treatment of skin disorders and protection of skin against environmental stressors.


Hair Follicle Stem Cells Topologically Associating Domains (TADs) Epidermal Differentiation Complex (EDC) Lineage-specific Gene Expression Programs Chromosome Territories 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.





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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Vladimir A. Botchkarev
    • 1
    • 2
    Email author
  • Andrey A. Sharov
    • 2
  • Michael Y. Fessing
    • 1
  1. 1.Centre for Skin SciencesUniversity of BradfordBradfordUK
  2. 2.Department of DermatologyBoston University School of MedicineBostonUSA

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