부산대학교 도서관

Most individuals with oculocutaneous albinism type 1 (OCA1) are compound heterozygotes with different maternal and paternal mutations of the tyrosinase gene. Approximately 15% of OCA1 alleles have no identifiable mutation in the coding or proximal promoter region of the gene suggesting that mutations in other regions of the gene, such as distal regulatory regions, may account for these unidentified mutations. We and others have previously identified a distal region of the tyrosinase gene that has enhancer activity. We now report functional analysis of the sequences flanking the 5′ distal enhancer region previously identified (NCBI accession AY367052) and show additional sequences critical for full activation of reporter genes. Constructs with sequential deletion of the 5′ end of the published enhancer sequence (EPP2) produced a loss of enhancer activity, while the addition of contiguous sequence to the 5′ end of EPP2 resulted in a significant increase in enhancer activity. These studies allow us to further define the critical regulatory sequences in this region by defining suppressor and enhancer elements of the human tyrosinase gene. This work reveals the complexity of the tyrosinase distal enhancer, and suggests regions of this critical gene that could contain changes associated with OCA1. [ABSTRACT FROM AUTHOR]