Mount Sinai Study: UV Exposure Produces Epigenetic Changes to Induce Skin Pigmentation

A new study out of Mount Sinai in New York has found that UV exposure produces epigenetic changes in the epidermis to induce skin pigmentation.
 
The paper, UV-induced reduction in Polycomb repression promotes epidermal pigmentation” was published on Sept. 1 in the journal Developmental Cell. The author is Elena Ezhkova, PhD, professor of cell, developmental and regenerative biology, and dermatology in the Black Family Stem Cell Institute at the Icahn School of Medicine at Mount Sinai, New York, and other coauthors. 
 
The sun's ultraviolet (UV) exposure causes DNA damage in epidermal cells and is a leading cause of skin cancers. To protect from the damaging effects of UV exposure, epidermal cells become pigmented by melanocytes, pigment producing cells. Taken up by epidermal cells, the melanin pigment absorbs UV light and reduces DNA damage. However, the molecular mechanisms of interaction between epidermal cells and melanocyte are not well understood.
 
The researchers found that UV causes a reduction in the expression of subunits of the Polycomb complex, a key transcriptional repressor, in epidermal cells. They discovered that reduced Polycomb levels in the epidermis led to an increased number of melanocytes and subsequent epidermal pigmentation—without UV exposure. They identified that the extracellular matrix protein type II collagen is a Polycomb target gene that is upregulated in UV-exposed epidermal cells and that is sufficient to drive pigmentation production in melanocytes and induce epidermal pigmentation. 
 
UV treatments are currently being used to treat patients with skin hypopigmentation conditions such as vitiligo. Mount Sinai researchers have found that epidermal application of the EZH2-specific inhibitors to the skin results in skin pigmentation without harmful UV exposure. Polycomb/Ezh2 inhibitors are currently being developed, with some progressing to clinical trials and an FDA approval. While the use of EZH2-specific inhibitors for treating hypopigmentation diseases will require studies in the future, this is an interesting new avenue of investigation, said the scientists behind the study.
 
“We are very excited about our findings, especially in the context of skin diseases such as pigmentation disorders as well as melanoma, aggressive skin cancer,” Mount Sinai's Dr. Ezhkova said about the research.  “Exposure to UV is a leading cause of melanoma. It is thought that a combination of factors, including genetic mutations in melanocytes, causes melanoma, but many of these factors are still unknown. Our studies show that UV-induced epigenetic changes in epidermal cells can alter behavior of melanocytes opening an interesting avenue of investigation if these changes in epidermal cells interact with oncogenic mutations in melanocytes to lead to melanoma formation”.

The research was supported by the National Institutes of Health. The Albert Einstein College of Medicine, RIKEN Center for Integrative Medical Sciences in Japan, the Ben-Gurion University of the Negev in Israel, and the University of Kentucky College of Medicine contributed to the study.