Negative control of the helix-loop-helix family of myogenic regulators in the NFB mutant.
We have characterized a nondifferentiating mouse muscle cell line, NFB, that represses the activity of the helix-loop-helix (HLH) family of myogenic regulators, yet expresses sarcomeric actins. The NFB MyoD gene is silent, but can be activated upon transfection of a long terminal region-controlled chicken MyoD cDNA, resulting in myogenesis. When NFB cells are fused with H9c2 rat muscle cells in heterokaryons, the level of rat MyoD transcripts declines. Thus, the stoichiometry of MyoD and the putative repressor controls myogenesis. Although NFB cells express myogenin and Myf-5 transcripts, the activity of these regulators is also repressed:myogenesis is not induced in 10T1/2 fibroblasts and is repressed in L6 muscle cells upon fusion with NFB cells. We conclude that the myogenic HLH regulators are not required for sarcomeric actin gene activation and that myogenesis is subject to dominant-negative control.
Department of Pharmacology, Stanford University School of Medicine, California 94305.
C A
CA
Peterson
H
H
Gordon
Z W
ZW
Hall
B M
BM
Paterson
H M
HM
Blau
D000199:Actins / Q000032:analysis / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D002454:Cell Differentiation; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005809:Genes, Regulator; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics* / Q000302:isolation & purification; D009132:Muscles; D009154:Mutation; D017570:MyoD Protein; D010641:Phenotype; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection
D000199:Actins; D009124:Muscle Proteins; D017570:MyoD Protein; D012333:RNA, Messenger; D012313:RNA; D004247:DNA; D005020:Ethyl Methanesulfonate