Characterization of human cardiac myosin heavy chain genes.

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Abstract
We have isolated and analyzed the structure of the genes coding for the .alpha. and .beta. forms of the human cardiac myosin heavy chain (MYHC). Detailed analysis of four overlapping MYHC genomic clones shows that the .alpha.-MYHC and .beta.-MYHC genes constitute a total length of 51 kilobases and are tandemly linked. The .beta.-MYHC-encoding gene, predominantly expressed in the normal human ventricle and also in slow-twitch skeletal muscle, is located 4.5 kilobases upstream of the .alpha.-MYHC-encoding gene, which is predominantly expressed in the normal human ventricle and also in slow-twitch skeletal muscle, is located 4.5 kilobases upstream of the .alpha.-MYHC-encoding gene, which is predominantly expressed in normal human atrium. We have determined the nucleotide sequences of the .beta. form of the MYHC gene, which is 100% homologous to the cardiac MYHC cDNA clone (pHMC3). It is unlikely that the divergence of a few nucleotide sequences from the cardiac .beta.-MYHC cDNA clone (pMHC3) reported in a MYHC cDNA clone (pSMHCZ) from skeletal muscle is due to a splicing mechanism. This finding suggests that the same .beta. form of the cardiac MYHC gene is expressed in both ventricular and slow-twitch skeletal muscle. The promoter regions of both .alpha.- and .beta.-MYHC genes, as well as the first four coding regions in the respective genes, have also been sequenced. The sequences in the 5''-flanking region of the .alpha.- and .beta.-MYHC-encoding genes diverge extensively from one another, suggesting that expression of the .alpha.- and .beta.-MYHC genes is independently regulated.