Most transcription factors are believed to be composed of independently functioning modules [A. D. Frankel and P. S. Kim (1991) Cell 65, 717-719]. Basic helix-loop-helix (bHLH) transcription factors appear to fit this model, with the HLH domains mediating dimerization, the basic regions mediating DNA binding, and other modules controlling other functions such as transcriptional activation. We tested predictions of this model using forced dimers of bHLH proteins including E47 homodimers and MyoD:E47 heterodimers and found that protein dimers containing complete bHLH domains but lacking other regions of E47 have only 20% of the DNA binding ability and transcriptional transactivation activity of wild-type dimers. These results demonstrate that the bHLH domains do not function as completely independent DNA binding modules. In addition, these results demonstrate that the transcriptional activation domains from a single bHLH protein are sufficient to activate transcription. (C) 2002 Elsevier Science (USA).