UV-induced reduction in Polycomb repression promotes epidermal pigmentation

Dev Cell. 2021 Sep 27;56(18):2547-2561.e8. doi: 10.1016/j.devcel.2021.08.006. Epub 2021 Sep 1.

Abstract

Ultraviolet (UV) radiation is a prime environmental stressor that our epidermis is exposed to on a daily basis. To avert UV-induced damage, epidermal stem cells (EpSCs) become pigmented via a process of heterotypic interaction between melanocytes and EpSCs; however, the molecular mechanisms of this interaction are not well understood. In this study, we show that the function of a key chromatin regulator, the Polycomb complex, was reduced upon UV exposure in human and mouse epidermis. Genetic ablation of key Polycomb subunits in murine EpSCs, mimicking depletion upon UV exposure, results in an increased number of epidermal melanocytes and subsequent epidermal pigmentation. Genome-wide transcriptional and chromatin studies show that Polycomb regulates the expression of UV-responsive genes and identifies type II collagen (COL2A1) as a critical secreted regulator of melanogenesis and epidermal pigmentation. Together, our findings show how UV exposure induces Polycomb-mediated changes in EpSCs to affect melanocyte behavior and promote epidermal pigmentation.

Keywords: Polycomb; UV; epidermis; melanocyte; pigmentation; stem cell; type II collagen.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Epidermal Cells / cytology*
  • Epidermis / metabolism*
  • Epidermis / pathology
  • Keratinocytes / metabolism
  • Melanocytes / metabolism*
  • Mice, Transgenic
  • Pigmentation / physiology
  • Skin Pigmentation / physiology
  • Stem Cells / cytology*
  • Ultraviolet Rays / adverse effects