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Figure 3


Fig. 3. Model of miR-1- and miR-133-mediated gene regulation during muscle proliferation and differentiation. Tissue-specific expression of miR-1 and miR-133 clusters is controlled by the transcription factors SRF, MEF2 and MyoD. miR-1 promotes muscle differentiation by repressing the expression of HDAC4 (histone deacetylase 4), a signal-dependent inhibitor of muscle differentiation that represses MEF2 activity. MEF2, in turn, potently activates the expression of myoblast-differentiation genes and miR-1. miR-133, however, reduces protein levels of SRF, a crucial regulator of muscle differentiation, thereby enhancing the proliferation of myoblasts and inhibiting their differentiation.





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