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 o f 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 myog enic cell line, C2, and in a derivative of this cell line where the my f5 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 synergis tically to rapidly up-regulate the levels of myf5 transcript and prote in, The glucocorticoid antagonist RU 486 abolishes this synergy, demon strating the involvement of the glucocorticoid receptor, The expressio n of a dominant negative mutant of c-jun which interferes with the tra nsactivating properties of all AP-1 family members also blocks the ind uction of myf5 by anisomycin and dexamethasone. An activator of protei n kinase C (PKCs), 12-O-tetradecanoyl phorbol 13-acetate (TPA), abolis hes the up-regulation of myf5 gene expression by dexamethasone and ani somycin, and its effect is counteracted by an inhibitor of PKCs, GF 10 9203X, These results point to the possible involvement of PKCs in the negative control of myf5, Evidence that both positive and negative reg ulation of myf5 transcripts, described here, does not require the fres h synthesis of transcription factors suggests that myf5 may behave lik e an immediate early gene.