CHARACTERIZATION OF THE GENE FOR THE MOUSE PROSTAGLANDIN-E RECEPTOR SUBTYPE EP2 - TISSUE-SPECIFIC INITIATION OF TRANSCRIPTION IN THE MACROPHAGE AND THE UTERUS

Genomic DNA clones for the mouse prostaglandin (PG) E receptor subtype EP2 were isolated and characterized. The mouse EP2 gene is composed o f 2 exons and 1 intron, and spans 16 kb. The intron which is approx. 1 2 kb in length is located at the end of the sixth transmembrane domain , as with other prostanoid receptor genes. Based on this structure, tr anscripts were analysed in endotoxin-treated macrophages and pseudopre gnant uteri, in which abundant expression of EP2 mRNA was observed. Se quence analysis of cDNA clones from these origins and Northern hybridi zation of these RNAs revealed that the uterine EP2 mRNA (U-type) has a longer 5'-untranslated region than the macrophage EP2 transcript (M-t ype). The major transcription initiation sites for M-type and U-type E P2 are located 124 and 769 bp upstream of the translation start site, respectively. The M-type was expressed in various tissues, whereas the U-type was found only in the uterus. The 2 kb segment containing the immediate 5'-flanking and 5'-noncoding regions contain three consensus sequences for the NF-IL6 binding site, one consensus sequence for the NF-kappa B binding site, four AP-2 consensus sequences, one AP-4 cons ensus sequence, one potential cAMP response element, and one potential progesterone response element. These results suggest that EP2 gene ex pression in the macrophage and uterus is under the control of distinct mechanisms involving alternative promoters.