The human red colour (RHC) trait is caused by increased pheomelanin (red-yellow) and reduced eumelanin (black-brown) pigment in skin and hair due to reduced melanocortin 1 receptor (MC1R) function. MC1R coding variants that give rise to RHC phenotypes are also a well-defined risk factor for melanoma; however, the mechanism remains unclear why decreased MC1R signalling in these variants alters pigmentation and increases melanoma susceptibility.
Matthew Berns, a member of the NIH Oxford-Cambridge Scholars Program, and colleagues in the Goding lab worked with the NIH to better understand the gene regulatory network (GRN) associated with the RHC trait by using single-cell RNA sequencing to compare melanocytes with both active and suppressed MC1R signalling. Their study elucidated a gene signature (MiGS) containing many genes which have been poorly studied in the context of melanocyte and melanoma biology. This included Tbx3, which they show can bind and regulate genes associated with pigmentation and cancer progression. Therefore, genes comprising the MiGS merit further investigation to further the understanding of by whichGRNs regulate melanocyte function and disease progression.
More information can be found in the full paper in Pigment Cell & Melanoma Research.