Genomic structure, chromosomal mapping, and muscle-specific expression of a PH domain-associated intronless gene, cded/lior

The aim of our study was to isolate novel gene(s) involved in cell differen tiation and embryonic liver development. Mouse cded/lior was identified fro m subtraction hybridization of embryonic liver cDNA libraries as well as an adult mouse liver genomic DNA library. The full open reading frame of cded /lior encodes a 131-amino acid protein with 71.88% overall similarity to th e PH domain of rat PLC-gamma 1. A gapped search with the C-terminal region of CDED/LIOR revealed a 36-41% similarity to several proteins related to si gnal transduction and cell replication, such as ORC1 and KSR. Northern blot analysis of adult mouse tissues shows a strong 2.6-kb transcript restricte d to heart and skeletal muscle. RT-PCR utilizing cded/lior-specific primers demonstrates cded/lior mRNAs in heart, brain, and liver tissue throughout mid-embryonic mouse gestation. cded/lior maps to the distal end of mouse Ch romosome (Chr) 2. Analysis of the genomic structure for cded/lior demonstra ted a single exon gene that is not an alternatively spliced isoform of PLC- gamma 1. Analysis of the cned/ lior promoter region revealed a high CC-cont ent, high ratio of CpG/GpC, multiple CC-boxes, the lack of a TATA box, CTF/ NFI element, and two MyoD-MCK binding sites. These characteristics are also found in several genes important in the regulation of cell growth or DNA s ynthesis, such as transforming growth factor-beta 1, c-Ha-ras, nerve growth factor, epidermal growth factor receptor, and DNA polymerase beta. These r esults suggest that cded/lior is a mesoderm/muscle-specific transcript that may be involved in the mesodermal inductive and regulatory interactions re quired for liver formation and embryonic development.