Gene structure and minimal promoter of mouse rdh1.

Mouse rdh1 encodes retinol dehydrogenase type 1 (RDH1), a short-chain dehydrogenase, which recognizes as substrates all-trans-retinol, 9-cis-retinol, 5alpha-androstan-3,17-diol and 5alpha-androstan-3-ol-17-one. RDH1 is the most efficient known mouse short-chain dehydrogenase that catalyzes dehydrogenation of all-trans-retinol, and contributes to a reconstituted path of all-trans-retinoic acid biosynthesis, when coexpressed in reporter cells with any one of three retinal dehydrogenases. Rdh1 shows widespread, if not ubiquitous, mRNA expression in the mouse beginning no later than embryo day 7. Here we report genomic organization, chromosomal localization and analysis of a minimum promoter of mouse rdh1. Rdh1 consists of four exons and three introns and spans approximately 14412 bp. Rdh1 is a single copy gene that maps to chromosome 10D3 with rdh5-9, but no known disorder maps precisely to rdh1. Rdh1 has three transcription start sites in kidney and one start site in liver. The rdh1 5'-region between -424 and +43 induces transcription maximally in COS7, mouse kidney RAG, and mouse liver NMu3Li cells. This section has no TATA box, but has a CCAAT box beginning 65 bp upstream of the major transcription start site, which is required for transcription of transfected reporter constructs. An AP1 binding site at -119 also activates transfected reporter constructs, and mediates 2-O-tetradecanoylphorbol-13-acetate (TPA) induced transcription. All-trans-retinoic acid antagonizes the TPA affect; however, no RARE or RXRE was found in the proximal promoter region, consistent with indirect regulation by all-trans-retinoic acid.