Members of the HNF-3/forkhead Family of Transcription Factors Exhibit Distinct Cellular Expression Patterns in Lung and Regulate the Surfactant Protein B Promoter
| Autor: | R. S. Peterson, Derek E. Clevidence, A. Porcella, D. G. Overdier, Honggang Ye, K. E. Paulson, Robert H. Costa |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Aging Proteolipids Recombinant Fusion Proteins Molecular Sequence Data Gene Expression Bronchi Biology digestive system Epithelium Rats Sprague-Dawley Embryonic and Fetal Development Mice Forkhead Transcription Factors Gene expression Consensus sequence Animals Amino Acid Sequence Promoter Regions Genetic Lung Molecular Biology Gene Peptide sequence Transcription factor In Situ Hybridization Gene Library Mice Inbred BALB C Base Sequence Sequence Homology Amino Acid Nuclear Proteins Pulmonary Surfactants Promoter Cell Biology Molecular biology Rats Pulmonary Alveoli Gene Expression Regulation Liver Organ Specificity embryonic structures Sequence motif Transcription Factors Developmental Biology |
| Zdroj: | Developmental Biology. 166:195-209 |
| ISSN: | 0012-1606 |
| DOI: | 10.1006/dbio.1994.1307 |
| Popis: | The hepatocyte nuclear factor-3 (HNF-3)/forkhead (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-3 alpha and HNF-3 beta are normally coexpressed in the hepatocyte, their expression patterns in the lung are different. The HNF-3 alpha and HFH-4 genes are coexpressed in the bronchiolar epithelium (clara cells), whereas the HNF-3 beta 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-3 alpha and HFH-8 genes, respectively. We show that the SPB-f2 sequence is recognized by both HNF-3 alpha 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-3 alpha and HFH-8 proteins in a cell type-specific manner. |
| Databáze: | OpenAIRE |
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