Members of the HNF-3/forkhead Family of Transcription Factors Exhibit Distinct Cellular Expression Patterns in Lung and Regulate the Surfactant Protein B Promoter

• Published in: Developmental biology Vol. 166; no. 1; pp. 195 - 209
• Main Authors: Clevidence, Derek E., Overdier, David G., Peterson, Richard S., Porcella, Anna, Ye, Honggang, Paulson, K.Eric, Costa, Robert H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-1994
• Subjects: Aging - metabolism; Amino Acid Sequence; amino acid sequences; Animals; Base Sequence; Bronchi - metabolism; cells; clara cells; complementary DNA; DNA-binding proteins; Embryonic and Fetal Development; Epithelium - metabolism; Forkhead Transcription Factors; genbank/l13201; genbank/l13204; genbank/l35949; Gene Expression; Gene Expression Regulation; Gene Library; genes; genetic activation; In Situ Hybridization; Liver - metabolism; Lung - cytology; Lung - metabolism; lungs; Male; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Nuclear Proteins - biosynthesis; Nuclear Proteins - metabolism; Organ Specificity; promoter regions; Promoter Regions, Genetic; Proteolipids - biosynthesis; Pulmonary Alveoli - metabolism; Pulmonary Surfactants - biosynthesis; Rats; Rats, Sprague-Dawley; Recombinant Fusion Proteins; sequence alignment; Sequence Homology, Amino Acid; smooth muscle cells; transcription (genetics); Transcription Factors - biosynthesis; Transcription Factors - metabolism
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1006/dbio.1994.1307

The hepatocyte nuclear factor 3 (HNF-3)/fork head (fkh) proteins consist of an extensive family of tissue-specific and developmental gene regulators which share homology within the winged helix DNA binding motif. We report on the isolation of a new family member, HNF-3/forkhead homolog 8 (HFH-8), from lung cDNA libraries and the derivation of the complete amino acid sequences for the HFH-8 protein as well as previously identified HFH-1 and HFH-4 proteins. The HFH proteins contain several sequence motifs found in activation domains of other transcription factors and HNF-3/fkh family members. In situ hybridization with the HNF-3, HFH-4, and HFH-8 probes in adult lung demonstrate that the HNF-3/fkh cellular expression patterns are regionally specified. Whereas HNF-3α and HNF-3β are normally coexpressed in the hepatocyte, their expression patterns in the lung are different. The HNF-3α and HFH-4 genes are coexpressed in the bronchiolar epithelium (clara cells), whereas the HNF-3β probe exhibits prominent hybridization with the smooth muscle surrounding arterioles and bronchioles. In contrast, HFH-8 probes labeled the type II pneumocyte cells lining the respiratory surfaces of terminal bronchioles and alveolar sac. We have identified an HNF-3 consensus DNA binding sequence in the proximal surfactant protein B (SPB) promoter region (SPB-f2, -78 to -88). SPB gene transcription is restricted to bronchiolar and alveolar epithelium which colocalizes with the expression pattern of the HNF-3α and HFH-8 genes, respectively. We show that the SPB-f2 sequence is recognized by both HNF-3α and HFH-8 proteins and that these cDNA expression vectors activate the SPB promoter in cotransfection assays through the HNF-3 consensus sequence. Our results suggest that SPB promoter activity is regulated by HNF-3α and HFH-8 proteins in a cell type-specific manner.