© 1993 Oxford University Press
RESEARCH-ARTICLE |
Five skeletal myosin heavy chain genes are organized as a multigene complex in the human genome
1Unité de Génétique Moléculaire Humaine Institut Pasteur 25, Rue du Dr. Roux, F-75724 Paris Cédex 15, France 2Unité de Biochimie, Département de Biologie Moléculaire, Institut Pasteur 25, Rue du Dr. Roux, F-75724 Paris Cédex 15, France
*To whom correspondence should be addressed
Received December 2, 1993; Revised March 8, 1993; Accepted March 8, 1993
Myosin heavy chain (MyHC) isoforms are encoded by a multigene family in vertebrates. We used genomic DNA mapping by pulse field gel electrophoresis to demortstrate that, in humans, the embryonic, fetal, fast IIB and IIX MyHC genes and a gene coding for a non-identified striated muscle MyHC fast-type isoform (NI), are contained within a 320 kb SalI genomic fragment. The locus is flanked by two CpG islands, separated by 580 kb. In order to further characterize the MyHC genes, a human genomic library constructed in yeast artificial chromosomes (YAC) was screened and five independent clones were Isolated. Characterization of these YACs revealed that one of them contains at least five MyHC genes, based on partial sequencing of their conserved third coding exons. Three of these genes correspond to those encoding the embryonic, fetal and fast IIB MyHC isoforms. Moreover, in this YAC done the embryonic and fetal genes, on the one hand, and the adult fast (IIB, IIX and NI) genes, on the other hand, are contained within two different ClaI fragments. This result suggests that the genes encoding the two developmental forms are adjacent In the human genome and that temporal regulation of the MyHC genes might be related to their organization within the locus. These data represent the first direct evidence for the existence in the human genome of a MyHC multigene locus that contains at least five genes.
+Present address: Institut Jacques Monod, Tour 43, Université Paris VII, 2 Place Jussieu, F-75251 Paris cedex 05, France
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