BASIC HELIX-LOOP-HELIX PROTEIN MYOD DISPLAYS MODEST DNA-BINDING SPECIFICITY

The expression of MyoD can activate muscle specific genes and myogenic differentiation in many cell types. The hypothesis that the DNA bindi ng specificity of MyoD is responsible for its biological specificity w as tested. Homodimers of MyoD bind to E-box containing DNA with high a ffinity, but do not form stable and web defined complexes with heterol ogous DNA sequences. The physiologically active heterodimer of MyoD an d E12 binds an oligonucleotide containing an E-box sequence with an af finity only two orders of magnitude higher than a completely unrelated DIVA sequence, stressing the importance of cooperative interactions w ith other proteins of the transcriptional machinery for specific gene activation.