Abstract
Clara cell secretory protein/uteroglobin (CCSP/UG) is specifically expressed in the conducting airway epithelium of the lung in a differentiation-dependent manner. The proximal promoter region of the rodent CCSP/UG gene directs Clara cell specificity. Previously, it was shown that the forkhead transcription factors HNF-3 alpha and beta and the homeodomain factor TTF-1 are important transcription factors acting through this region, suggesting that they contribute to cell specificity of the CCSP/UG gene. Members of the C/EBP family of transcription factors can also interact with elements of the proximal rat and mouse CCSP/UG promoters. The onset of C/EBP alpha expression in Clara cells correlates with the strong increase of CCSP/UG expression. Thus, C/EBP alpha may play a crucial role for differentiation-dependent CCSP/UG expression. Transfection studies demonstrate that C/EBP alpha and TTF-1 can synergistically activate the murine CCSP/UG promoter. Altogether, these results suggest that C/EBP alpha, TTF-1, and HNF-3 determine the Clara cell-specific, differentiation-dependent expression of the CCSP/UG gene in murine lung. The relative importance of these three transcription factors, however, differs in rabbits and humans.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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CCAAT-Enhancer-Binding Proteins / genetics
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CCAAT-Enhancer-Binding Proteins / metabolism
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Cell Differentiation / genetics*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation, Developmental / physiology*
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Hepatocyte Nuclear Factor 3-alpha
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Humans
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Lung / cytology
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Lung / embryology*
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Lung / metabolism*
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Mice
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Promoter Regions, Genetic / physiology
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Proteins / genetics*
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Proteins / metabolism
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RNA, Messenger / metabolism
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Rabbits
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Respiratory Mucosa / cytology
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Respiratory Mucosa / embryology*
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Respiratory Mucosa / metabolism*
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Species Specificity
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Thyroid Nuclear Factor 1
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Transcription Factor CHOP
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription, Genetic / physiology
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Uteroglobin*
Substances
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CCAAT-Enhancer-Binding Proteins
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DDIT3 protein, human
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DNA-Binding Proteins
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Ddit3 protein, mouse
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FOXA1 protein, human
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Foxa1 protein, mouse
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Hepatocyte Nuclear Factor 3-alpha
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NKX2-1 protein, human
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Nkx2-1 protein, mouse
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Nuclear Proteins
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Proteins
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RNA, Messenger
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SCGB1A1 protein, human
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Scgb1a1 protein, mouse
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Scgb1a1 protein, rat
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Thyroid Nuclear Factor 1
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Transcription Factors
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Transcription Factor CHOP
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Uteroglobin