A genome-wide genetic screen uncovers determinants of human pigmentation.
Science
; 381(6658): eade6289, 2023 08 11.
Article
en En
| MEDLINE
| ID: mdl-37561850
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pigmentación de la Piel
/
Melanosomas
/
Proteínas Adaptadoras Transductoras de Señales
/
Factor 6 Similar a Kruppel
/
Melaninas
/
Melanocitos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos