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Science 21 October 1988:
Vol. 242. no. 4877, pp. 405 - 411
DOI: 10.1126/science.3175662

Articles

Science, Vol 242, Issue 4877, 405-411
Copyright © 1988 by American Association for the Advancement of Science


articles

MyoD1: a nuclear phosphoprotein requiring a Myc homology region to convert fibroblasts to myoblasts

SJ Tapscott, RL Davis, MJ Thayer, PF Cheng, H Weintraub, and AB Lassar

Department of Genetics, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.

Expression of a complementary DNA (cDNA) encoding the mouse MyoD1 protein in a variety of fibroblast and adipoblast cell lines converts them to myogenic cells. Polyclonal antisera to fusion proteins containing the MyoD1 sequence show that MyoD1 is a phosphoprotein present in the nuclei of proliferating myoblasts and differentiated myotubes but not expressed in 10T1/2 fibroblasts or other nonmuscle cell types. Functional domains of the MyoD1 protein were analyzed by site-directed deletional mutagenesis of the MyoD1 cDNA. Deletion of a highly basic region (residues 102 to 135) interferes with both nuclear localization and induction of myogenesis. Deletion of a short region (residues 143 to 162) that is similar to a conserved region in the c-Myc family of proteins eliminates the ability of the MyoD1 protein to initiate myogenesis but does not alter nuclear localization. Deletions of regions spanning the remainder of MyoD1 did not affect nuclear localization and did not inhibit myogenesis. Furthermore, expression of only 68 amino acids of MyoD1, containing the basic and the Myc similarity domains, is sufficient to activate myogenesis in stably transfected 10T1/2 cells. Genetic analysis maps the MyoD1 gene to mouse chromosome 7 and human chromosome 11.


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R. Davis and H Weintraub (1992)
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T Braun, E Bober, and H H Arnold (1992)
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The neural tube/notochord complex is necessary for vertebral but not limb and body wall striated muscle differentiation.
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Development 115, 657-672
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Genes & Dev. 5, 2342-2352
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Muscle-specific transcriptional activation by MyoD..
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Regulation of achaete-scute gene expression and sensory organ pattern formation in the Drosophila wing..
J B Skeath and S B Carroll (1991)
Genes & Dev. 5, 984-995
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HNF-1 alpha and HNF-1 beta (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro..
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Genes & Dev. 5, 1042-1056
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Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc.
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The myoD gene family: nodal point during specification of the muscle cell lineage.
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MyoD family: a paradigm for development?.
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Genes & Dev. 4, 567-581
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Myogenin resides in the nucleus and acquires high affinity for a conserved enhancer element on heterodimerization..
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Genes & Dev. 4, 582-595
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HNF-1 shares three sequence motifs with the POU domain proteins and is identical to LF-B1 and APF..
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TFE3: a helix-loop-helix protein that activates transcription through the immunoglobulin enhancer muE3 motif..
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Science 247, 467-470
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Science 246, 780-786
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5-bromo-2'-deoxyuridine blocks myogenesis by extinguishing expression of MyoD1.
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Science 245, 532-536
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An avian muscle factor related to MyoD1 activates muscle-specific promoters in nonmuscle cells of different germ-layer origin and in BrdU-treated myoblasts..
Z Y Lin, C A Dechesne, J Eldridge, and B M Paterson (1989)
Genes & Dev. 3, 986-996
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A gene with homology to the myc similarity region of MyoD1 is expressed during myogenesis and is sufficient to activate the muscle differentiation program..
D G Edmondson and E N Olson (1989)
Genes & Dev. 3, 628-640
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Phosphoinositide 3-Kinase Induces the Transcriptional Activity of MEF2 Proteins during Muscle Differentiation.
Y. Tamir and E. Bengal (2000)
J. Biol. Chem. 275, 34424-34432
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Rac1 Inhibits Myogenic Differentiation by Preventing the Complete Withdrawal of Myoblasts from the Cell Cycle.
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Stabilization of MyoD by Direct Binding to p57Kip2.
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J. Biol. Chem. 275, 18767-18776
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