Myogenin, one of the four myogenic regulatory factors (MRFs), plays a pivotal role in the terminal differentiation of skeletal muscles. The regulation of myogenin expression during skeletal myogenesis is a very complex event. Previous work showed that MyoD (another MRF) and myocyte enhancer factor 2C (MEF2C) activated myogenin expression through the conserved E-box (CANNTG) and A/T rich MEF2 consensus sequences respectively. However, how the intracellular signaling pathways in turn regulate MyoD and MEF2 remains unknown. This work aimed to uncover the regulatory mechanisms by which multiple signaling pathways regulate myogenin expression. We showed that IGF-PI3K-Akt, p38 MAPK, as well as calcium signaling pathways (CaM kinase and calcineurin) participated in activating MyoD and MEF2C, w...[ Read more ]

Myogenin, one of the four myogenic regulatory factors (MRFs), plays a pivotal role in the terminal differentiation of skeletal muscles. The regulation of myogenin expression during skeletal myogenesis is a very complex event. Previous work showed that MyoD (another MRF) and myocyte enhancer factor 2C (MEF2C) activated myogenin expression through the conserved E-box (CANNTG) and A/T rich MEF2 consensus sequences respectively. However, how the intracellular signaling pathways in turn regulate MyoD and MEF2 remains unknown. This work aimed to uncover the regulatory mechanisms by which multiple signaling pathways regulate myogenin expression. We showed that IGF-PI3K-Akt, p38 MAPK, as well as calcium signaling pathways (CaM kinase and calcineurin) participated in activating MyoD and MEF2C, which in turn activated myogenin expression at the transcriptional level. Recently a conserved MEF3 site was identified to be an indispensable cis-element in the myogenin promoter, and we showed that the pathways mentioned above targeted this site as well.