Genomic organization and expression of the rat TRPM-2 (clusterin) gene, a gene implicated in apoptosis

Abstract

We describe the genomic structure of the rat TRPM-2 gene. This gene is induced de novo during the regression of the prostate and other hormone-dependent tissues after hormone ablation and plays an important role in apoptosis, or active cell death. TRPM-2 is a single copy gene, organized into nine exons, ranging in size from 47 base pairs (exon I) to 412 base pairs (exon IV), spanning a region of 13,750 base pairs. Comparison with sequences registered in the data bases shows that it has extensive homology to SGP-2, a gene that is expressed constitutively in the testis, although the sequences diverge dramatically in the 5'-untranslated region of the mRNA (coded for by exon I in TRPM-2), raising the possibility of alternative exon I usage in SGP-2. Primer extension, S1 nuclease protection, and extensive polymerase chain reaction analysis suggest that the TRPM-2 transcript from the prostate and the SGP-2 transcript from the testis are in fact identical and only contain the exon I sequence identified in the TRPM-2 genomic clone. Analysis of the promoter region of the TRPM-2 gene demonstrates that the putative control region contains several potential regulatory elements that may regulate the complex tissue-specific control of a gene which must be constitutively expressed in some tissues but repressed in others until induced during active cell death.