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The peripheral clock regulates human pigmentation.

Jonathan A Hardman1, Desmond J Tobin2, Iain S Haslam3

  • 1The Centre for Dermatology Research, Institute of Inflammation and Repair, University of Manchester, Manchester, UK; Doctoral Training Centre in Integrative Systems Biology, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK.

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The study reveals that the molecular clock, specifically genes BMAL1 and PER1, directly controls human hair follicle pigmentation. Disrupting these clock genes boosts melanin production, suggesting new therapeutic targets for pigmentation disorders.

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Area of Science:

  • Molecular Biology
  • Dermatology
  • Chronobiology

Background:

  • Pigmentation regulation is understood, but cell-autonomous controls of hair follicle (HF) pigmentation cycling are unclear.
  • Human HFs and melanocytes express clock genes, and core clock genes (PER1, BMAL1) influence HF cycling.

Purpose of the Study:

  • To investigate if peripheral clock activity influences human HF pigmentation.
  • To elucidate the role of the molecular clock in regulating melanogenesis within HFs and skin.

Main Methods:

  • Silencing of BMAL1 or PER1 genes in human HFs and isolated melanocytes.
  • Analysis of melanin content, tyrosinase expression and activity, melanocyte markers (gp100), and melanocyte morphology.
  • Investigated downstream effects on microphthalmia-associated transcription factor (MITF) phosphorylation.

Main Results:

  • Silencing BMAL1 or PER1 significantly increased melanin content in human HFs and skin.
  • Key melanogenesis markers (tyrosinase, TYRP1/2, gp100) and melanocyte activity were upregulated.
  • BMAL1/PER1 silencing directly enhanced melanocyte tyrosinase activity and TYRP1/2 expression in vitro.

Conclusions:

  • The molecular clock acts as a cell-autonomous regulator of human pigmentation.
  • BMAL1 and PER1 silencing stimulate melanogenesis via MITF phosphorylation.
  • The molecular clock presents a potential therapeutic target for modulating human pigmentation.