J. Vervoorts et B. Luscher, DNA binding of Myc/Max/Mad network complexes to oligonucleotides containing two E box elements: c-Myc/Max heterodimers do not bind DNA cooperatively, BIOL CHEM, 380(9), 1999, pp. 1121-1126
Myc proteins function in heterodimeric complexes with Max proteins as trans
criptional regulators at least in part by binding to E box sequences with a
5'-CACGTG core. Since such E boxes are found frequently in the human genom
e and since other proteins besides Myc/Max can bind to similar or identical
sequences it is unclear how the specificity of E box-mediated gene transcr
iption is determined. Recent findings were interpreted to suggest that Myc/
Max, but not Max/Max or USF complexes, bind cooperatively to DNA sequences
that contain two E box elements. This provides a potential mechanism for se
lective E box-mediated gene transcription. To extend this finding we analyz
ed DNA binding of c-Myc/Max complexes using a transient COS-7 expression sy
stem. In both competition and titration experiments no cooperative binding
of c-Myc/Max heterodimers to probes with two E boxes was observed. Furtherm
ore, c-Myc-specific transcription of reporter gene constructs did not revea
l cooperativity. Thus our findings argue against cooperative DNA binding of
Myc proteins as a selection mechanism for E box-dependent transcription.