Some higher vertebrates can display unique muscle regenerative abilities through dedifferentiation. Research evidence suggests that induced dedifferentiation can be achieved in mammalian cells. TWIST is a bHLH (basic helix-loop-helix) transcription factor that is expressed during embryonic development and plays critical roles in diverse developmental systems including myogenesis. Several experiments demonstrated its role in inhibition of muscle cell differentiation. We have previously shown that overexpression of TWIST can reverse muscle cell differentiation in the presence of growth factors. Here we show that TWIST reverses muscle cell differentiation through binding and down-regulation of myogenin. Moreover, it can reverse cellular morphology in the absence of growth factors.