Fig. 4: Population-specific 923 enhancer: IVL promoter/intron alleles and eQTLs impact regulatory activity.
From: Selective sweep for an enhancer involucrin allele identifies skin barrier adaptation out of Africa
a Schematic of population-specific human 923 enhancer (red), IVL promoter (light blue), 1st exon, and intron (dark blue) alleles with IVL eQTLs. Positions of variants not to scale. Colored boxed variants are associated with relatively lower IVL expression levels to human reference. Positively selected iSAFE SNPs for CEU in orange. b Luciferase assays of population-specific alleles for the IVL promoter/intron + respective enhancer reveals that the CEU promoter/intron allele has the highest regulatory activity (Proliferating: p = 0.003 vs. JPT/CHB; p = 0.025 vs. YRI; Differentiated: p = 0.008 vs. JPT/CHB; p = 0.001 vs. YRI). The addition of the enhancer confers higher reporter expression with more activity in CEU (p = 0.003) and YRI (p = 0.024) than JPT/CHB and especially in differentiated cells for CEU vs. JPT/CHB (p = 0.047). Mean ± SEM of n independent experiments (n = 3, IVL promoter/intron) and (n = 4, 923 enhancer + IVL promoter/intron), one-way ANOVA followed by Tukey’s HSD. c Position weight matrices (PWM) for candidate transcription factor binding motifs in reference and alternate alleles at rs1974141, rs4845327, rs1854779, & rs7517189 associated with population-specific regulatory activity. Strand sequence with SNP included for comparison to PWM.
