Epigenetic regulators and skin pigmentation
The epidermis provides the body essential protection from external stressors. The epidermis is composed of epidermal stem cells (EpSCs) that continuously fuel the production of several layers of differentiated cells that perform protective functions. Solar UV irradiation is a key environmental stressor. UV irradiation, particularly its UV component, induces DNA damage in EpSCs and excessive exposure to UV is a well-known cause of skin cancer. To avert UV-induced damage, EpSCs express paracrine factors that activate melanocytes to transfer melanin to EpSCs. The pigmentation provides the protective function as melanin absorbs UV photons while reducing UV penetration. However, the molecular mechanisms of UV-mediated changes in gene expression in EpSCs that promote the production of melanogenetic factors, eventually inducing epidermal pigmentation, are largely unknown. Chromatin regulators are potential candidates to mediate UV-induced transcriptional changes in the epidermis. Indeed, the activities of many chromatin regulators are known to be sensitive to environmental agents and can thereby serve as sensors through which these environmental agents alter gene expression. Polycomb repressive complex 2 (PRC2) and PRC1 are critical epigenetic chromatin regulators that function together to establish Polycomb-mediated gene repression. Therefore, we will focus on dissecting the role of PRCs in regulating the key transcriptional network in the EpSCs that controls proper McSCs function and skin pigmentation upon UV irradiation. Our goal will ultimately help us to develop therapeutic strategies to treat skin pigmentation disorders like Vitiligo and Melasma.