The Peripheral Clock Regulates Human Pigmentation

The study investigated the role of peripheral clock genes, specifically BMAL1 and PER1, in regulating human hair follicle (HF) pigmentation. It was found that silencing these genes in human HFs led to an increase in melanin content, as well as an upregulation of various pigmentation markers such as tyrosinase activity, TYRP1 and TYRP2 mRNA levels, and gp100 protein expression. Additionally, silencing these genes in isolated melanocytes directly increased tyrosinase activity and TYRP1/2 expression. The mechanism behind this involves BMAL1 knockdown reducing PER1 transcription, while PER1 silencing induces phosphorylation of the microphthalmia-associated transcription factor, a key regulator of melanogenesis. These findings suggest that the molecular clock acts as a cell-autonomous modulator of human pigmentation, presenting potential targets for therapeutic strategies. The number of participants or samples was not specified in the summary provided.