Fig. 4. MEF2 and mammalian skeletal myogenesis. Upstream inductive signals activate the expression of MYOD and MYF5, which activate the expression of myogenin in skeletal myocytes. Myogenin activates MEF2 expression, which feeds back on the myogenin promoter to amplify and maintain its expression. Myogenin and MEF2 also autoregulate their own promoters. MEF2, together with myogenic bHLH factors, activates genes involved in muscle differentiation. In addition, MEF2 activates HDAC9 expression, providing a negative-feedback loop that can be modulated by upstream signals that regulate HDAC9 phosphorylation. MEF2 also regulates the expression of the microRNA miR-1, which represses HDAC4 translation, thereby providing a positive-feedback loop for myogenesis.