Evolutionary conservation of MyoD function and differential utilization of E proteins.
The 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, and Caenorhabditis elegans. Various MyoD and E factor combinations were tested for their ability to interact in vitro and to function in vivo in the myogenic conversion of 10T12 mouse fibroblasts. We found that the ability of different homo- and heterodimers to bind DNA in vitro was an accurate measure of biological activity in vivo. A second assessment of conserved function comes from the ability of these factors to rescue a C. elegans hlh-1 (CeMyoD) null mutation. We found that both Drosophila and chicken MyoD-related factors were able to rescue a C. elegans CeMyoD loss-of-function mutation. These results demonstrate a remarkable degree of functional conservation of these myogenic factors despite differences in E-protein interactions.
Zhang
J M
JM
Laboratory of Biochemistry, NCI, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Chen
L
L
Krause
M
M
Fire
A
A
Paterson
B M
BM
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D017173:Caenorhabditis elegans / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D002645:Chickens; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D004330:Drosophila; D005347:Fibroblasts / Q000166:cytology; D005816:Genetic Complementation Test; D018257:Helix-Loop-Helix Motifs; D051379:Mice; D009132:Muscles / Q000166:cytology*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; D017570:MyoD Protein; D051820:TCF Transcription Factors; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors