The mouse γ-glutamyl transpeptidase gene is transcribed from at least five separate promoters

The mouse γ-glutamyl transpeptidase (γGT) gene encodes six distinct mRNAs that differ in their 5'-untranslated regions but appear to code for the same protein. To elucidate the mechanisms that generate these different mRNAs we determined the transcription start sites of γGT kidney mRNAs and investigated the ability of the 5'-flanking regions of mRNAs I, II, IV, V, and VI to direct transcription of chloramphenicol acetyltransferase (CAT) reporter gene constructs in a mouse kidney cell line. Types I, II, and VI mRNAs show heterogenous start sites, whereas types IV and V have more precise initiation sites. Only the V 5'-flanking region contains a TATA-like element. The highest CAT activities were observed with 416 base pairs of type II and 240 base pairs of type IV flanking regions. We have also shown that types II and IV represent the predominant γGT mRNAs in kidney; therefore, these CAT activities correlate well with the relative amount of each γGT mRNA. This study shows that the mouse γGT gene is transcribed from at least five and possibly six different promoters. In addition, the γGT promoters show cell specificity because no significant CAT activity was detected when these constructs were introduced into NIH-3T3 fibroblasts.