Selective regulation of the atrial natriuretic peptide gene by individual components of the activator protein-1 complex.
We used the human atrial natriuretic peptide (hANP) gene as a model to investigate the causal relationship between immediate early gene expression and the subsequent activation of the embryonic gene repertoire in cardiac hypertrophy. Using transient transfection analysis, we found that overexpression of individual Jun family members, alone or in combination, displayed unique activity that varied as a function of the promoter and the nature of the transfected myocyte populations under examination. In neonatal cardiac ventriculocytes, both c-jun and to a lesser extent, JunB stimulated hANP promoter activity (approximately 7- and 3- fold, respectively). When cotransfected together, a synergistic activation was observed (approximately 16-fold activation), a finding that stands in contrast to the behavior of JunB (i.e. neutral or inhibitory) with other 12-O- tetradeconoylphorbol 13-acetate response element-dependent promoters. In atriocytes, on the other hand, JunB did not itself activate the hANP promoter, and it antagonized c-jun- mediated transcription. JunD, a third member of this gene family, was devoid of activity in these transfected cultures. These findings suggest that the hANP gene promoter exhibits a broad range of responses to the individual products of the jun gene family. The response in any single situation is a function of the relative concentrations and subunit composition of the prevailing activator protein-1 complexes.
Kovacic-Milivojevic
B
B
Department of Medicine, University of California, San Francisco, California 94143-0540, USA.
Wong
V S
VS
Gardner
D G
DG
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis* / Q000235:genetics; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
D018808:Transcription Factor AP-1; D009320:Atrial Natriuretic Factor