In FY90, the Genetic Pharmacology Unit concentrated on the molecular regulation of neurotransmitter and transmitter receptor genes. Two model systems were studied: 1) Regulation of POMC gene transcription: Studies done in FY90 were based on earlier findings in this laboratory about several exonuclease stop sites in the 1Kb 5' flanking region of the mouse POMC gene suggesting the presence of a number of potential sites for DNA-protein interaction. Two of these have been characterized in detail. One located between -119 and -106 bp upstream from transcription start site is homologous to the transcription factor AP-2 thought to be involved in signal transduction, and the other located between -137 and -131 has 70% homology to, but is distinct from, AP-1. 2) Regulation of striatal dopamine receptor genes: This project was initiated in FY90. For the D-2 receptor, a full length cDNA clone was characterized and the 5' region sequenced. Screening a rat genomic library has yielded several candidate clones that are currently being characterized. Similarly for the D-1 receptor, screening a human genomic library with the recently cloned rat D-1 receptor cDNA that is coupled to adenylate cyclase has yielded 13 candidate clones. Current studies focus on characterizing the promoter region of these genes and study their transcriptional regulation.
