Transcriptional regulation of S100A1 and expression during mouse heart development

S100A1, a member of the large EF-hand family of Ca2+-binding proteins, is m ainly expressed in the mammalian heart. To assess the underlying mechanisms for cell- and tissue-specific expression we isolated and characterized the mouse S100A1 gene. The gene displays a high degree of homology to the huma n and rat genes, especially in the exonic sequences. In its promoter region and the first intron, we identified regulatory elements characteristic for cardiac and slow skeletal muscle restricted genes. Transfection assays wit h luciferase constructs containing different parts of the S100A1 gene demon strated the active expression in primary mouse cardiomyocytes and that its 5'-upstream region containing a putative cardiac enhancer showed a greatly increased activity. Furthermore, we investigated the expression of the S100 A1 mRNA during embryonic mouse development, using in situ hybridization. S1 00A1 transcripts were first detected in the primitive heart at embryonic da y (E) 8, with equal levels in the atrium and ventricle. During development up to E17.5 we detected a shift in the S100A1 expression pattern with lower levels in atrial and high levels in ventricular myocardium. The regulatory elements identified in the mouse S100A1 promoter correspond well with the observed expression pattern and suggest that S100A1 has an important functi on during heart muscle development. (C) 2000 Elsevier Science B.V. All righ ts reserved.