Sequence-specific DNA-binding activators, key regulators of gene expression, 
stimulate transcription in part by targeting the core promoter recognition TFIID 
complex and aiding in its recruitment to promoter DNA. Although it has been 
established that activators can interact with multiple components of TFIID, it 
is unknown whether common or distinct surfaces within TFIID are targeted by 
activators and what changes if any in the structure of TFIID may occur upon 
binding activators. As a first step toward structurally dissecting 
activator/TFIID interactions, we determined the three-dimensional structures of 
TFIID bound to three distinct activators (i.e., the tumor suppressor p53 
protein, glutamine-rich Sp1 and the oncoprotein c-Jun) and compared their 
structures as determined by electron microscopy and single-particle 
reconstruction. By a combination of EM and biochemical mapping analysis, our 
results uncover distinct contact regions within TFIID bound by each activator. 
Unlike the coactivator CRSP/Mediator complex that undergoes drastic and global 
structural changes upon activator binding, instead, a rather confined set of 
local conserved structural changes were observed when each activator binds 
holo-TFIID. These results suggest that activator contact may induce unique 
structural features of TFIID, thus providing nanoscale information on 
activator-dependent TFIID assembly and transcription initiation.