A genome-wide genetic screen uncovers determinants of human pigmentation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37561850.
- Also identified by DOI 10.1126/science.ade6289 and PMC identifier 10901463.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Skin color, one of the most diverse human traits, is determined by the quantity, type, and distribution of melanin. In this study, we leveraged the light-scattering properties of melanin to conduct a genome-wide screen for regulators of melanogenesis. We identified 169 functionally diverse genes that converge on melanosome biogenesis, endosomal transport, and gene regulation, of which 135 represented previously unknown associations with pigmentation. In agreement with their melanin-promoting function, the majority of screen hits were up-regulated in melanocytes from darkly pigmented individuals. We further unraveled functions of KLF6 as a transcription factor that regulates melanosome maturation and pigmentation in vivo, and of the endosomal trafficking protein COMMD3 in modulating melanosomal pH. Our study reveals a plethora of melanin-promoting genes, with broad implications for human variation, cell biology, and medicine.
Medical subject headings
- Melanins
- Melanocytes
- Melanosomes
- Skin Pigmentation
- Adaptor Proteins, Signal Transducing
- Kruppel-Like Factor 6