Figure 2. The human blond-associated region contains a functional hair enhancer.

(a) A 17.1 kb region bounded by SNPs rs444647 and rs661114 defines the candidate interval for blondness². Within this region, a large block of mammalian sequence conservation overlaps peak marker rs12821256. Five human fragments were cloned upstream of a lacZ reporter gene and tested for in vivo enhancer activity in transgenic mice. (b–f) Representative transgenic embryos generated by pronuclear microinjection of different lacZ constructs, processed at E16.5 to reveal lacZ gene activity (blue staining). Scale bar, 1 mm. (b) H1. (c) H2. (d) H3. (e) HFE (for hair follicle enhancer). (f) H2b. Of the three clones spanning the entire interval, only the 6.7 kb clone, H2, produced consistent lacZ expression in skin and kidney (arrow). Analysis of two subclones from H2 separated HFE skin (e) and H2b kidney (f, arrow) enhancers. (g,h) 6 µm crosssections through E16.5 dorsal skin from (g) H2 and (h) HFE transgenic embryos counterstained with nuclear fast red. Strong lacZ expression is visible in the basal epithelium and developing hair follicles. Scale bar, 30 µm.