Evolutionary Conservation of MyoD Function and Differential Utilization of E Proteins

AbstractThe formation of striated muscle in both vertebrates and invertebrates involves the activity of the MyoD family of basic-helix-loop-helix (bHLH) transcription factors. The high degree of evolutionary conservation of MyoD-related proteins, both in the sequence of their bHLH domains and in their general developmental expression patterns, suggests that these factors are also conserved at the level of function. We have addressed this directly using MyoD and E protein factors from vertebrates,Drosophila,andCaenorhabditis elegans.Various MyoD and E factor combinations were tested for their ability to interactin vitroand to functionin vivoin the myogenic conversion of 10T12mouse fibroblasts. We found that the ability of different homo- and heterodimers to bind DNAin vitrowas an accurate measure of biological activityin vivo.A second assessment of conserved function comes from the ability of these factors to rescue aC. elegans hlh-1(CeMyoD) null mutation. We found that bothDrosophilaand chicken MyoD-related factors were able to rescue aC. elegansCeMyoD loss-of-function mutation. These results demonstrate a remarkable degree of functional conservation of these myogenic factors despite differences in E-protein interactions