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A genome-wide genetic screen uncovers determinants of human pigmentation

Bajpai, Vivek K ; Swigut, Tomek ; Mohammed, Jaaved ; Naqvi, Sahin ; Arreola, Martin ; Tycko, Josh ; Kim, Tayne C ; Pritchard, Jonathan K ; Bassik, Michael C ; Wysocka, Joanna

Science (American Association for the Advancement of Science), 2023-08, Vol.381 (6658), p.eade6289-eade6289 [Periódico revisado por pares]

United States: The American Association for the Advancement of Science

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Título:
A genome-wide genetic screen uncovers determinants of human pigmentation
Autor: Bajpai, Vivek K ; Swigut, Tomek ; Mohammed, Jaaved ; Naqvi, Sahin ; Arreola, Martin ; Tycko, Josh ; Kim, Tayne C ; Pritchard, Jonathan K ; Bassik, Michael C ; Wysocka, Joanna
Assuntos: Adaptation ; Adaptor Proteins, Signal Transducing - genetics ; Adaptor Proteins, Signal Transducing - metabolism ; Animals ; Cell Line, Tumor ; Cell lines ; Color ; CRISPR ; Deletion ; Deoxyribonucleic acid ; DNA ; DNA damage ; Endosomes - metabolism ; Flow cytometry ; Gene regulation ; Genes ; Genetic screening ; Genetics ; Genome-Wide Association Study ; Genomes ; Hair ; Human populations ; Humans ; Kruppel-Like Factor 6 - genetics ; Kruppel-Like Factor 6 - metabolism ; Light ; Light levels ; Light scattering ; Maturation ; Melanin ; Melanins - biosynthesis ; Melanins - genetics ; Melanocytes ; Melanocytes - metabolism ; Melanosomes ; Melanosomes - metabolism ; Mice ; Optical properties ; Perturbation ; pH effects ; Physicochemical properties ; Pigmentation ; Polymers ; Population studies ; Populations ; Protein transport ; Refractivity ; RNA processing ; RNA transport ; Scattering ; Skin ; Skin pigmentation ; Skin Pigmentation - genetics ; Synthesis ; Transcription factors ; Variation
É parte de: Science (American Association for the Advancement of Science), 2023-08, Vol.381 (6658), p.eade6289-eade6289
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
These authors contributed equally
Author contributions: V.K.B. conceived of and designed the study, performed experiments, analyzed data including bioinformatic analyses of CRISPR screen, and wrote the manuscript with input from all co-authors; V.K.B. performed FACS experiments with help from M.A. and T.C.K.; T.C.K. did blinded melanosome counting of TEM images; J.T. and M.B. provided advice and technical support with CRISPR screening; J.M. and S.N. performed evolutionary adaptation and heritability analyses, respectively; J.K.P. provided advice on evolutionary selection and heritability analyses; T.S. performed RNA-seq analyses and provided advice on data analyses and experimental design; J.W. conceptualized and supervised the project and cowrote the manuscript with V.K.B.
Descrição: 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.
Editor: United States: The American Association for the Advancement of Science
Idioma: Inglês

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A genome-wide genetic screen uncovers determinants of human pigmentation

Bajpai, Vivek K ; Swigut, Tomek ; Mohammed, Jaaved ; Naqvi, Sahin ; Arreola, Martin ; Tycko, Josh ; Kim, Tayne C ; Pritchard, Jonathan K ; Bassik, Michael C ; Wysocka, Joanna

United States: The American Association for the Advancement of Science

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