Mutations of the tyrosinase gene produce oculocutaneous albinism type 1 (OCA1). Most affected individuals are compound heterozygotes with different maternal and paternal mutations, but a substantial number of presumed tyrosinase alleles in these individuals have no identifiable mutation in the coding or proximal promoter region of the gene. This suggests that mutations in other regions of the gene, such as regulatory regions that are removed from the direct proximity of the coding sequence, may account for these currently unidentifiable mutations. The mouse tyrosinase gene has a distal enhancer or locus control region (LCR) that provides position-independent stimulation of gene expression, and a homologous regulatory region (HR) of the human gene could be the site of some of these mutations. We report a region 9 kb upstream of the human tyrosinase transcriptional start site that may be involved in regulation of this gene. Analysis of this region shows DNase I hypersensitivity in a cell lineage-specific pattern, a pattern indicative of regulatory regions of a gene. This region also has significant enhancer function when reporter vectors containing it are transfected into either human or mouse melanocyte cell lines, and elimination of specific sequences with homology to the mouse core enhancer in this region extinguishes the enhancer function. We believe that this region of homology contains sequences critical in the regulation of the human tyrosinase gene and is a candidate for the location of OCA1 mutations.
- Oculocutaneous albinism