The discovery of the skeletal muscle-specific transcription factor MyoD represents a milestone in the field of transcriptional regulation during differentiation and cell-fate reprogramming. MyoD was the first tissue-specific factor found capable of converting non-muscle somatic cells into skeletal muscle cells. A unique feature of MyoD, with respect to other lineage-specific factors able to drive trans-differentiation processes, is its ability to dramatically change the cell fate even when expressed alone. The present review will outline the molecular strategies by which MyoD reprograms the transcriptional regulation of the cell of origin during the myogenic conversion, focusing on the activation and coordination of a complex network of co-factors and epigenetic mechanisms. Some molecular roadblocks, found to restrain MyoD-dependent trans-differentiation, and the possible ways for overcoming these barriers, will also be discussed. Indeed, they are of critical importance not only to expand our knowledge of basic muscle biology but also to improve the generation skeletal muscle cells for translational research.
Keywords: MyoD; chromatin regulation; forced differentiation; myogenic conversion.