THE MOUSE GAMMA-GLUTAMYL-TRANSPEPTIDASE GENE IS TRANSCRIBED FROM AT LEAST 5 SEPARATE PROMOTERS

The mouse gamma-glutamyl transpeptidase (gamma GT) gene encodes six di stinct mRNAs that differ in their 5'-untranslated regions but appear t o code for the same protein. To elucidate the mechanisms that generate these different mRNAs we determined the transcription start sites of gamma GT kidney mRNAs and investigated the ability of the 5'-flanking regions of mRNAs I, II, IV, V, and VI to direct transcription of chlor amphenicol acetyltransferase (CAT) reporter gene constructs in a mouse kidney cell line. Types I, II, and VI mRNAs show heterogenous start s ites, whereas types TV and V have more precise initiation sites. Only the type V 5'-flanking region contains a TATA-like element. The highes t 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 gamma GT mRNAs in kidney; therefor e, these CAT activities correlate well with the relative amount of eac h gamma GT mRNA. This study shows that the mouse gamma GT gene is tran scribed from at least five and possibly six different promoters. In ad dition, the gamma GT promoters show cell specificity because no signif icant CAT activity was detected when these constructs were introduced into NIH-3T3 fibroblasts.