Structural characterization of the human fast skeletal muscle troponin I gene (TNNI2)

Three troponin I genes have been identified in vertebrates that encode the isoforms expressed in adult cardiac muscle (TNNI3), slow skeletal muscle (T NNI1) and fast skeletal muscle (TNNI2), respectively. While the organizatio n and regulation of human cardiac and slow skeletal muscle genes have been investigated in detail, the fast skeletal troponin I gene has to date only been examined in birds. Here, we describe the structure and complete sequen ce of the human fast skeletal muscle troponin I gene (TNNI2) and identify p utative regulatory elements within both the 5' flanking region and the firs t intron. In particular, a region containing MEF-2, E-box, CCAC and CAGG el ements was identified in intron 1 that closely resembles the fast internal regulatory element (FIRE) of the quail intronic enhancer. We have previousl y shown that the fast skeletal muscle troponin I gene is located at 11p15.5 and noted potential close linkage with the fast skeletal muscle troponin T gene (TNNT3). Here, we have isolated two independent human PAC genomic clo nes that contain either TNNI2 or TNNT3 and demonstrate by interphase FISH m apping that they are less than 100 kb apart in the genome. The results demo nstrate that the human TNNI2 gene is closely related to its avian counterpa rts with conserved elements within both the putative promoter and first int ron. Our data further confirm close physical linkage of TNNI2 and TNNI3 on 11p15.5. (C) 2000 Elsevier Science B.V. All rights reserved.