Myf5 is a member of the MyoD family, a set of four helix-loop-helix tr
anscription factors that controls myogenic differentiation. The Myf5 g
ene has both in vivo and in vitro expression patterns consistent with
an involvement in the first events of myogenesis, such as acquisition
and/or maintenance of myogenic ''determined'' phenotype. To date, very
little is known about the mechanism underlying the tight regulation o
f Myf5 expression. We report here that retinoic acid (RA) reduces the
level of Myf5 message in both mouse C2 and rat L6 cell lines, probably
at the transcriptional level, because Myf5 mRNA stability is not affe
cted by RA. This repression is dose dependent, starting at 0.1 mum of
all-trans RA, and is not abrogated by cycloheximide, suggesting a dire
ct involvement of RA receptors in the control of Myf5 expression. Furt
hermore, we compared the efficiency of natural (all-trans RA and 9-cis
RA) or synthetic (TTNPB) retinoids that differentially activate the t
wo families of RA receptors, RA receptors and retinoid X-receptors (9-
cis RA). As 9-cis RA is about 10 times more efficient than all-trans R
A in repressing Myf5, whereas TTNPB, which preferentially activates RA
receptors, is far less potent, our data provide evidence for an impor
tant role of ligand-bound retinoid X-receptors in the mediation of thi
s inhibition.