Functional Conservation of the Promoter Regions of Vertebrate Tyrosinase Genes

The Fourth Annual Meeting of the Dermatology Forum for Basic Research and Treatment

Shigeru Sato ; Mika Tanaka ; Hirohito Miura ; Kazuho Ikeo ; Takashi Gojobori ; Takuji Takeuchi ; Hiroaki Yamamoto

Others  :  http://www.nature.com/jidsp/journal/v6/n1/pdf/5640019a.pdf
PID  :  5260

来源: CEUR

【 摘 要 】

Tyrosinase is the key enzyme for synthesizing melanin pigments, which primarily determine mammalian skin coloration. Considering the important roles of pigments in the evolution and the adaptation of vertebrates, phylogenetic changes in the coding and ¯anking regulatory sequences of the tyrosinase gene are particularly intriguing. We have now cloned cDNA encoding tyrosinase from Japanese quail and snapping turtle. These nonmammalian cDNA are highly homologous to those of the mouse and human tyrosinases, whereas the 5¢ ¯anking sequences are far less conserved except for a few short sequence motifs. Nevertheless, we demonstrate that the 5¢ ¯anking sequences from the quail or turtle tyrosinase genes are capable of directing the expression of a fused mouse tyrosinase cDNA when introduced into cultured mouse albino melanocytes. This experimental method, which reveals the functional conservation of regulatory sequences in one cell type (the melanocyte), may be utilized to evaluate phylogenetic differences in mechanisms controlling speci®c gene expression in many other types of cells. We also provide evidence that the 5¢ ¯anking sequences from these nonmammalian genes are functional in vivo by producing transgenic mice. Phylogenetic changes of vertebrate tyrosinase promoters and the possible involvement of conserved sequence motifs in melanocyte- speci®c expression of tyrosinase are discussed. [First Paragraph]