ISOLATION AND CHARACTERIZATION OF THE HUMAN CARDIAC TROPONIN-I GENE (TNNI3)

Troponin I (TnI) is a constituent protein of the troponin complex loca ted on the thin filament of striated muscle that provides a calcium-se nsitive switch for striated muscle contraction. Unlike other contracti le proteins, the cardiac isoform of troponin I (TnIc) is expressed onl y in cardiac muscle and therefore offers a model for cardiac-specific expression. It is also subject to developmental regulation with increa sed expression occurring at the time of birth, Here we describe the is olation and characterization of the human TnIc gene (HGMW-approved sym bol TNNI3) and its promoter. The gene comprises eight exons contained within 6.2 kb of genomic DNA. The proximal promoter and 1.1-kb 5'-flan king region were sequenced, and several putative cis-acting elements t hat are conserved between the human and tile mouse TnIc genes were ide ntified. In addition, multiple copies of a 37-bp chromosome 19-specifi c mini-satellite sequence were identified within this region. Followin g transfection, 2300 bp of 5' sequence is active in both cardiac myocy tes and skeletal muscle cells but is inactive in fibroblasts, indicati ng that it can drive expression but is insufficient to confer cardiac specificity. (C) 1996 Academic Press, Inc.