PRIMARY STRUCTURE OF HEPATOCYTE NUCLEAR FACTOR FORKHEAD HOMOLOG-4 ANDCHARACTERIZATION OF GENE-EXPRESSION IN THE DEVELOPING RESPIRATORY ANDREPRODUCTIVE EPITHELIUM/

Members of the winged helix/forkhead family of transcription factors a re believed to play a role in cell-specific gene expression, A cDNA en coding a member of this family of proteins, termed hepatocyte nuclear factor/forkhead homologue 4 (HFH-4), has been isolated from rat lung a nd rat testis cDNA libraries. This cDNA contains an open reading frame of 421 amino acids with a conserved DNA binding domain and several po tential transactivating regions, During murine lung development, a sin gle species of HFH-4-specific transcript (2.4 kb long) is first detect ed precisely at the start of the late pseudoglandular stage (embryonic day 14.5) and, by in situ hybridization, is specifically localized to the proximal pulmonary epithelium. The unique temporal and spatial pa ttern of HFH-4 gene expression in the developing lung defines this pro tein as a marker for the initiation of bronchial epithelial cell diffe rentiation and suggests that it may play an important role in cell fat e determination during lung development, In addition to expression in the pulmonary epithelium, RNA blot analysis reveals 2.4 kb HFH-4 trans cripts in the testis and oviduct, By using mice with genetic defects i n spermatogenesis, HFH-4 expression in the testis is found to be assoc iated with the appearance of haploid germ cells and in situ hybridizat ion studies indicate that HFH-4 expression is confined to stages I-W o f spermatogenesis, This pattern of HFH-4 gene expression during the ea rly stages of differentiation of haploid germ cells suggests that HFH- 4 may play a role in regulating stage-specific: gene expression and ce ll-fate determination during lung development and in spermatogenesis,