It is important to understand how the organization of the genome meets the specialized requirements of an organism as complex as the mammal. The goal of this proposal is to study the relationship of DNA sequence organization and function in the mammalian genome. The human myosin heavy chain genes and interspersed repetitive DNA sequences will be studied, particularly as their positions and expression relate to structural gene expression. The myosin heavy chain (MHC) genes code for proteins that are responsible for motility in muscle and nonmuscle systems. The MHC proteins from both systems have very similar function and structure, yet their genes are quite divergent. Nonmuscle MHC genes will be isolated and chromosomally mapped. The organization and sequence of nonmuscle MHC genes will be compared with muscle-specific MHC genes that have been isolated and partially characterized (Leinwand et al. 1983 a & b). A somatic cell genetic approach will be carried out to analyze factors that regulate tissue and developmental-specific expression of muscle and nonmuscle MHC genes. The organization of specific repetitive DNA sequence families in the MHC multigene complex(es) will be determined as well as the muscle-specific expression of any repetitive sequences tested. While analyzing the organization and function of repetitive DNA sequences within the vicinity of the MHC genes, the investigation of the organization and expression of the repetitive sequences scattered throughout the genome will be continued. The interrelationships of repetitive DNA sequences and the muscle and nonmuscle myosin heavy chain genes will provide a better understanding of the link between genomic organization and function.
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