THE HUMAN PROSTATE-SPECIFIC TRANSGLUTAMINASE GENE (TGM4) - GENOMIC ORGANIZATION, TISSUE-SPECIFIC EXPRESSION, AND PROMOTER CHARACTERIZATION

Human prostate-specific transglutaminase (hTG(P)) is a cross-linking e nzyme secreted by the prostate. In this study, we performed dot blot a nalysis of 50 normal human tissues to demonstrate unambiguously the pr ostate-specific expression of hTG(P). Furthermore, we elucidated the g enomic organization of the TGM4 gene, the gene encoding hTG(P). The st ructure of this gene displays striking similarity to that of other tra nsglutaminase (TGase) genes. The TGM4 gene spans approximately 35 kb o f genomic DNA and consists of 13 exons and 12 introns. The main transc ription initiation site is located 52 bp upstream of the translational start codon. A hTG(P) splice variant of intron 1 was detected. This s plice variant contains an in-frame antisense Alu element insertion. Th e TGM4 promoter was analyzed by sequencing and transfection experiment s. At positions -1276 to -563, the promoter harbors a cyclophilin pseu dogene with 94% similarity to the cyclophilin A cDNA. Deletion mapping of the TGM4 promoter in the transiently transfected human prostate ca ncer cell line PC346C showed comparable activity of 2.1-, 1.5-, and 0. 5-kb promoter fragments. (C) 1998 Academic Press