The human prostate-specific transglutaminase gene (TGM4): Genomic organization, tissue-specific expression, and promoter characterization

Human prostate-specific transglutaminase (hTGp) is a cross-linking enzyme secreted by the prostate. In this study, we performed dot blot analysis of 50 normal human tissues to demonstrate unambiguously the prostate-specific expression of hTGp. Furthermore, we elucidated the genomic organization of the TGM4 gene, the gene encoding hTGp. The structure of this gene displays striking similarity to that of other transglutaminase (TGase) genes. The TGM4 gene spans approximately 35 kb of genomic DNA and consists of 13 exons and 12 introns. The main transcription initiation site is located 52 bp upstream of the translational start codon. A hTGp splice variant of intron 1 was detected. This splice variant contains an in-frame antisense Alu element insertion. The TGM4 promoter was analyzed by sequencing and transfection experiments. At positions -1276 to -563, the promoter harbors a cyclophilin pseudogene with 94% similarity to the cyclophilin A cDNA. Deletion mapping of the TGM4 promoter in the transiently transfected human prostate cancer cell line PC346C showed comparable activity of 2.1-, 1.5-, and 0.5-kb promoter fragments.

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