A. Greenall et al., DNA binding by the ETS-domain transcription factor PEA3 is regulated by intramolecular and intermolecular protein protein interactions, J BIOL CHEM, 276(19), 2001, pp. 16207-16215
The control of DNA binding by eukaryotic transcription factors represents a
n important regulatory mechanism. Many transcription factors are controlled
by cis-acting autoinhibitory modules that are thought to act by blocking p
romiscuous DNA binding in the absence of appropriate regulatory cues. Here,
we have investigated the determinants and regulation of the autoinhibitory
mechanism employed by the ETS-domain transcription factor, PEA3. DNA bindi
ng is inhibited by a module composed of a combination of two short motifs l
ocated on either side of the ETS DNA-binding domain. A second type of prote
in, Ids, can act in trans to mimic the effect of these cia-acting inhibitor
y motifs and reduce DNA binding by PEA3. By using a one-hybrid screen, we i
dentified the basic helix-loop-helix-leucine zipper transcription factor US
F-1 as an interaction partner for PEA3. PEA3 and USF-1 form DNA complexes i
n a cooperative manner. Moreover, the formation of ternary PEA3 USF-1 DNA c
omplexes requires parts of the same motifs in PEA3 that form the autoinhibi
tory module. Thus the binding of USF-1 to PEA3 acts as a switch that modifi
es the autoinhibitory motifs in PEA3 to first relieve their inhibitory acti
on, and second, promote ternary nucleoprotein complex assembly.