A genome-wide genetic screen uncovers novel determinants of human pigmentation
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PROVIDER: PRJNA1076455 | ENA |
REPOSITORIES: ENA
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Project description:A genome-wide genetic screen uncovers novel determinants of human pigmentation
| PRJNA942912 | ENA
Project description:To study the differentially expressed genes in lightly and darkly pigmented human skin melanocytes, we isolated melanocytes from light and dark skin samples and performed RNA-seq using Illumina platform.
2024-02-17 | GSE255752 | GEO
Project description:To study the differentially expressed genes in lightly and darkly pigmented human skin melanocytes, we isolated melanocytes from light and dark skin samples and performed RNA-seq using Illumina platform.
2023-08-11 | GSE227015 | GEO
Project description: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.
| S-EPMC10901463 | biostudies-literature
Project description:Skin color is highly variable in Africans, yet little is known about the underlying molecular mechanism. We identified 1,157 candidate variants influencing skin pigmentation in indigenous Africans by genome-wide association studies and scans of natural selection based on differentiation in allele frequencies between lightly pigmented southern African Khoesan populations and other darkly pigmented African populations. We applied massively parallel reporter and chromosome conformation capture assays to identify novel regulatory variants and their target genes related to skin pigmentation in melanocytic cells. We identified 165 SNPs showing strong differential regulatory activities between alleles. Combining CRISPR-mediated genome editing, transcriptome profiling and melanin assays, we identified causal regulatory variants impacting pigmentation near MFSD12/HMG20B, MITF, OCA2, and DDB1/CYB561A3/TMEM138. We identified CYB561A3 as a novel gene regulating pigmentation by impacting genes involved in oxidative phosphorylation and melanogenesis. Our results broaden our understanding of the genetic basis of human skin color diversity and human adaptation. To test the role of candidate enhancers and variants in skin pigmentation, we performed CRISPR inhibition or knockout of enhancers containing the functional variants identified by MPRA in melanocytic cells. Then, we performed gene expression profiling analysis using data obtained from RNA-seq of these CRISPR-edited cells. We also performed RNA-seq using CYB561A3-koncout MNT1 cells or CYB561A3-overexpressing MNT1 cells
2022-09-15 | GSE213142 | GEO
Project description:Skin color is highly variable in Africans, yet little is known about the underlying molecular mechanism. Here we applied massively parallel reporter assays to screen 1,157 candidate variants influencing skin pigmentation in Africans and identified 165 single-nucleotide polymorphisms showing differential regulatory activities between alleles. We combine Hi-C, genome editing and melanin assays to identify regulatory elements for MFSD12, HMG20B, OCA2, MITF, LEF1, TRPS1, BLOC1S6 and CYB561A3 that impact melanin levels in vitro and modulate human skin color. We found that independent mutations in an OCA2 enhancer contribute to the evolution of human skin color diversity and detect signals of local adaptation at enhancers of MITF, LEF1 and TRPS1, which may contribute to the light skin color of Khoesan-speaking populations from Southern Africa. Additionally, we identified CYB561A3 as a novel pigmentation regulator that impacts genes involved in oxidative phosphorylation and melanogenesis. These results provide insights into the mechanisms underlying human skin color diversity and adaptive evolution.
2023-08-11 | GSE240717 | GEO
Project description:Resistance to the first approved BCL-2 inhibitor venetoclax is emerging in lymphoid malignancies. The study aimed to identify the genetic determinants of such resistance. From genome-scale screens we determined the genes influencing the sensitivity to BCL-2 inhibition. The present set of data is related to expression changes (assessed by RNA sequencing) observed in the resistant OCI-Ly1 lymphoma cell line as well as those resulting from genetic perturbation (using CRISPR-Cas9) targeting the genes highlighted in our genome-scale screen.
2019-09-25 | GSE128563 | GEO
Project description:Skin color is highly variable in Africans, yet little is known about the underlying molecular mechanism. We identified 1,157 candidate variants influencing skin pigmentation in indigenous Africans by genome-wide association studies and scans of natural selection based on differentiation in allele frequencies between lightly pigmented southern African Khoesan populations and other darkly pigmented African populations. We applied massively parallel reporter and chromosome conformation capture assays to identify novel regulatory variants and their target genes related to skin pigmentation in melanocytic cells. We identified 165 SNPs showing strong differential regulatory activities between alleles. Combining CRISPR-mediated genome editing, transcriptome profiling and melanin assays, we identified causal regulatory variants impacting pigmentation near MFSD12/HMG20B, MITF, OCA2, and DDB1/CYB561A3/TMEM138. We identified CYB561A3 as a novel gene regulating pigmentation by impacting genes involved in oxidative phosphorylation and melanogenesis. Our results broaden our understanding of the genetic basis of human skin color diversity and human adaptation. To identify candidate enhancers and regulatory regions in skin pigmentation, we performed CUT&RUN and ATAC assays in two melanocytic cell lines (MNT-1 and WM88). We used the darkly pigmented MNT-1 cell line because it is widely used for studying skin pigmentation and it has a transcription pattern similar to normal melanocytes. We used the WM88 cell line because the cells are lightly pigmented and may have a different trans-environment (e.g., different levels of transcription factors and open chromatin regions) compared with MNT-1 cells. To identify regulatory regions in MNT-1 cells, we conducted CUT&RUN assays using antibodies against H3K4me3, H3K27ac, MITF and SOX10. We further performed ATAC-seq in both MNT-1 and WM88 cells to identify open chromatin regions.
2023-08-31 | GSE240716 | GEO
Project description:Purple carrots can accumulate large quantities of anthocyanins in their roots. Depending on the genetic background, anthocyanin pigmentation can be expressed in the entire root, or it can display tissue specific-patterns, confined to the root phloem or xylem tissues. Within the phloem, the tissue usually contributing most of the overall anthocyanin concentration in the carrot root, purple pigmentation can be found in the outer phloem (OP) (also called cortex) and inner phloem (IP) tissues, or it can be confined exclusively to the OP. The latter is a fairly-common phenotype in many purple carrot cultivars. In this work, the genetic control underlying tissue-specific anthocyanin pigmentation in the carrot root OP and IP tissues was investigated by means of linkage mapping, transcriptome (RNA-seq), phylogenetic, and gene expression (RT-qPCR) analyses in two genetic backgrounds; an F2 mapping population (3242) and the inbred line B7262. Genetic mapping of the ‘root outer phloem anthocyanin pigmentation’ (ROPAP) and inner phloem pigmentation (RIPAP) revealed co-localization of ROPAP with the P1 and P3 genomic regions previously known to condition pigmentation in different genetic stocks, whereas RIPAP co-localized with P3 only. Transcriptome analysis of purple OP (POP) vs. non-purple IP (NPIP) tissues, along with linkage and phylogenetic data, allowed an initial identification of 28 candidate genes, 19 of which were further evaluated by RT-qPCR in independent root samples of 3242 and B7262, revealing 15 genes consistently upregulated in the POP in both genetic backgrounds, and two genes upregulated in the POP in specific backgrounds. These include seven transcription factors (4 MYBs, 1 bHLH, 1 MADS-box, 1 ERF), seven anthocyanin structural genes, and two genes involved in cellular transport. Altogether, our results point at DcMYB7, DcMYB113, and a MADS-box (DCAR_010757) as the main candidate genes conditioning ROPAP in 3242, whereas DcMYB7 and MADS-box condition RIPAP in this background. In 7262, which roots present purple pigmentation only in the outer phloem, DcMYB113 conditions ROPAP
2021-10-27 | GSE181611 | GEO
Project description:Genetic screen of the yeast environmental stress response dynamics uncovers a succession of regulatory phases
| PRJNA525648 | ENA