|Budget Amount *help
¥6,200,000 (Direct Cost : ¥6,200,000)
Fiscal Year 1995 : ¥1,500,000 (Direct Cost : ¥1,500,000)
Fiscal Year 1994 : ¥4,700,000 (Direct Cost : ¥4,700,000)
When taken up in the cells, environmental pollutants usually represented by 2,3,7,8 tetrachlorodibenzodioxin exert various adverse biologicl effects such as teratogenesis, tumour promotion, immuno-decifiency, and epidermal dysplasia, in addition to induction of drug-metabolizing enzymes. These effects are considered to be mediated by Ah receptor (AhR). we cloned cDNA for AhR and deduced its primary structure from sequence analysis, which turned out to be a receptor-type transcription factor with novel bHLH and PAS domains at its N-terminus. The PAS is designated as a conserved sequence among Drosophila Per, Arnt (Ah receptor nuclear translocator) and Drosophila Sim.
Immunochemical analysis revealed that AhR andarnt form a complex to bind the XRE sequence, an inducible enhancer sequence to in response to ducers. The AhR/Arnt complex enhanced in vitro transcription of CYP1A1 gene in cooperation with Sp1, mimicking the transcription of the gene in the DNA transfer experiments. The two transcription factors interacted with each other on their cognate DNA elements to enhance the transcription. cDNA clones of novel members of the b/HLH/PAS family were isolated from cDNA libraries of mouse embryos and their expressions were investigated by the RNA blot hybridization and whole mount in situ hybridization. They were expressed specifically in the limited tissues of the developing embryos, suggesting the functional roles in the development. One of the clones is mSim, a mouse counterpart of the human gene which is suggested to be a causative gene for Down Syndrome.