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Published February 1, 1990 | Published
Journal Article Open

Herculin, a Fourth Member of the MyoD Family of Myogenic Regulatory Genes

Abstract

We have identified and cloned herculin, a fourth mouse muscle regulatory gene. Comparison of its DNA and deduced amino acid sequences with those of the three known myogenic genes (MyoD, myogenin, and Myf-5) reveals scattered short spans with similarity to one or more of these genes and a long span with strong similarity to all three. This long span includes a sequence motif that is also present in proteins of the myc, achaete-scute, and immunoglobulin enhancer-binding families. The herculin gene is physically linked to the Myf-5 gene on the chromosome; only 8.5 kilobases separate their translational start sites. A putative 27-kDa protein is encoded by three exons contained within a 1.7-kilobase fragment of the herculin gene. When expressed under the control of the simian virus 40 early promoter, transfected herculin renders murine NIH 3T3 and C3H/10T1/2 fibroblasts myogenic. In doing so, it also activates expression of myogenin, MyoD, and endogenous herculin in NIH 3T3 recipients. In adult mice, herculin is expressed in skeletal muscle but is absent from smooth muscle, cardiac muscle, and all nonmuscle tissues assayed. Direct comparison of the four known myogenic regulators in adult muscle showed that herculin is expressed at a significantly higher level than is any of the others. This quantitative dominance suggests an important role in the establishment or maintenance of adult skeletal muscle.

Additional Information

© 1990 by National Academy of Sciences Communicated by Norman Davidson, November 16, 1989. The sequence reported in this paper has been deposited in the GenBank data base (accession no. M30499). We thank A. Lassar, E. Olson, and H. Arnold for mouse MyoD, myogenin, and human Myf-5 cDNAs, respectively; R. Perlmutter and L. Hood for the genomic library; members ofthe Wold group and J. Johnson for RNA samples; S. Hauschka for myosin heavy chain antibody; S. Tavtigian for help with sequencing; K. Lee for technical assistance; H. Lester for use of computing facilities; A. Beggs for valuable discussions; and members of the Wold group for critical reading of the manuscript. J.H.M. was supported by a National Science Foundation Graduate Fellowship and a National Research Service Award. This work was supported by a grant from the Muscular Dystrophy Association to B.W. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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August 22, 2023
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October 13, 2023