REGULATION OF THE HUMAN INOSINE MONOPHOSPHATE DEHYDROGENASE TYPE-I GENE - UTILIZATION OF ALTERNATIVE PROMOTERS

Catalysis of guanine nucleotide formation from IMP in the de novo puri ne synthetic pathway is carried out by two isoforms of the enzyme inos ine monophosphate dehydrogenase (IMPDH) that are catalytically indisti nguishable but are encoded by separate genes, In order to assess the p otential for cell type-specific expression of IMPDH activity, we have characterized the IMPDH type I gene and identified three major RNA tra nscripts that are differentially expressed from three different promot ers, A 4.O-kilobase pair (kb) mRNA containing 1.3 kb of 5'-untranslate d region is expressed in activated peripheral blood lymphocytes and to a far lesser extent in cultured tumor cell lines, The Pi promoter tha t regulates the transcription of this mRNA has a high degree of sequen ce identity to an Alu repetitive sequence, A transcript of 2.7 kb is f ound in a subset of the tumor cell lines examined, whereas a 2.5-kb mR NA species is universally expressed and is the prevalent mRNA in most cell lines and tissues. The relative strengths of the three promoter r egions and the effects of variable extents of 5'-flanking sequence on the P3 promoter differ in Jurkat T, as compared with Raji B lymphoid c ell lines, demonstrating a complex cell type-specific transcriptional regulation of IMPDH type I gene expression.