Genomic organisation of the human cyclic AMP-specific phosphodiesterase PDE4C gene and its chromosomal localisation to 19p13.1, between RAB3A and JUND

PDE4C is one of four mammalian genes that encode multiple PDE4 cyclic AMP-s pecific phosphodiesterase isoforms that are inhibited by rolipram. Fluoresc ent in situ hybridisation localised PDE4C to the p13.1 region of human chro mosome 19. Overlapping cosmid clones spanning the human PDE4C gene were ide ntified and characterised. Analysis of this locus indicated that the PDE4C gene spans at least 38 kb, consists of at least 18 exons, and contains the marker D19S212 within an intron. Comparison of published human PDE4C cDNA s equences with those of the genomic DNA identified four alternatively splice d exons and the possibility that the PDE4C locus contains at least three al ternative promoters. PDE4C-containing cosmids also contained the genes for the growth regulatory transcription factor, JUND, and the mini guanine nucl eotide regulatory protein, RAB3A. The RAB3A gene was shown to consist of 5 exons spanning 7.9 kb, while the JUND gene was found to contain no introns. Analysis of cosmids containing PDE4C, JUND, and RAB3A showed that 27 kb se parate JUND and PDE4C, while only 3.7 kb separate PDE4C and RAB3A. The thre e genes share the same orientation of transcription and are arranged in the order cen-5'-JUND-PDE4C-RAB3A-3'-tel. CELL SIGNAL 11;10:735-742, 1999. (C) 1999 Elsevier Science Inc.