Regulation of the Clara cell secretory protein/uteroglobin promoter in lung.
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.
Nord
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Department of Medical Nutrition, Karolinska Institute, NOVUM, Huddinge University Hospital, SE-141 86 Huddinge, Sweden. magnus.nord@mednut.ki.se
Cassel
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Braun
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Suske
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D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051541:Hepatocyte Nuclear Factor 3-alpha; D006801:Humans; D008168:Lung / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020545:Respiratory Mucosa / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D013045:Species Specificity; D000074482:Thyroid Nuclear Factor 1; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D014598:Uteroglobin
D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; C497250:Ddit3 protein, mouse; C496499:FOXA1 protein, human; C496500:Foxa1 protein, mouse; D051541:Hepatocyte Nuclear Factor 3-alpha; C000614412:NKX2-1 protein, human; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; C556389:SCGB1A1 protein, human; C556390:Scgb1a1 protein, mouse; C556391:Scgb1a1 protein, rat; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D051742:Transcription Factor CHOP; D014598:Uteroglobin