The glucocorticoid receptor and AP-1 are involved in a positive regulation of the muscle regulatory gene myf5 in cultured myoblasts.
The muscle regulatory factor, myf5, is involved in the establishment of skeletal muscle precursor cells. Little is known, however, about the control of the expression of the gene encoding this basic helix-loop-helix (bHLH) factor. We have addressed this question in the mouse myogenic cell line, C2, and in a derivative of this cell line where the myf5 gene is the only muscle-specific bHLH factor to be expressed at the myoblast stage. We present evidence that the synthetic glucocorticoid dexamethasone, and the pharmacological agent anisomycin, act synergistically to rapidly up-regulate the levels of myf5 transcript and protein. The glucocorticoid antagonist RU 486 abolishes this synergy, demonstrating the involvement of the glucocorticoid receptor. The expression of a dominant negative mutant of c-jun which interferes with the transactivating properties of all AP-1 family members also blocks the induction of myf5 by anisomycin and dexamethasone. An activator of protein kinase C (PKCs), 12-O-tetradecanoyl phorbol 13-acetate (TPA), abolishes the up-regulation of myf5 gene expression by dexamethasone and anisomycin, and its effect is counteracted by an inhibitor of PKCs, GF 109203X. These results point to the possible involvement of PKCs in the negative control of myf5. Evidence that both positive and negative regulation of myf5 transcripts, described here, does not require the fresh synthesis of transcription factors suggests that myf5 may behave like an immediate early gene.
Auradé
F
F
Groupe de Développement Cellulaire, Institut Pasteur, Department of Molecular Biology, Paris, France.
Pfarr
C M
CM
Lindon
C
C
Garcia
A
A
Primig
M
M
Montarras
D
D
Pinset
C
C
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D018257:Helix-Loop-Helix Motifs; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D051787:Myogenic Regulatory Factor 5; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D011965:Receptors, Glucocorticoid; D015534:Trans-Activators; D018808:Transcription Factor AP-1