Characterization of promoter elements required for cardiac chamber-specific expression.
Salmon cardiac natriuretic peptide (sCP, an A-type natriuretic peptide) is an excellent model for the study of cardiac chamber-specific gene expression because it is uniquely specific to the heart and its promoter drives gene expression effectively in mammalian cardiac atrial but not in ventricular cells. We have now prepared hybrid luciferase constructs containing specific sequences from both sCP and BNP 5' promoters. According to our results the simple addition of a short rat BNP proximal promoter fragment to the inert 846 nucleotide sCP proximal promoter increases 100 times the basal activity of the sCP promoter in rat ventricular cardiomyocytes, and also conveys inducibility by mechanical load and endothelin-1. Thus, a small rBNP promoter fragment can transform the prototypical A-type natriuretic peptide regulation of sCP to B-type regulation, a result which argues against a major role of repressors causing the low expression level of A-type peptides in ventricular cardiomyocytes.
Majalahti
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T
Department of Physiology, Institute of Biomedicine, Biocenter Oulu, University of Oulu, Oulu, Finland.
Tokola
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H
Ruskoaho
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H
Vuolteenaho
O
O
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D024202:Electrophoretic Mobility Shift Assay; D019332:Endothelin-1 / Q000494:pharmacology; D029941:Fish Proteins / Q000235:genetics; D050980:GATA Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D045265:Natriuretic Peptides / Q000235:genetics; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D013314:Stress, Mechanical; D018808:Transcription Factor AP-1 / Q000378:metabolism; D024363:Transcription Initiation Site
D019332:Endothelin-1; D029941:Fish Proteins; D050980:GATA Transcription Factors; D045265:Natriuretic Peptides; D018808:Transcription Factor AP-1; C403482:cardiac natriuretic peptide, Salmo salar; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain