We showed earlier that p300/CBP plays an important role in G1 progression by 
negatively regulating c-Myc and thereby preventing premature G1 exit. Here, we 
have studied the mechanism by which p300 represses c-Myc and show that in 
quiescent cells p300 cooperates with histone deacetylase 3 (HDAC3) to repress 
transcription. p300 and HDAC3 are recruited to the upstream YY1-binding site of 
the c-Myc promoter resulting in chromatin deacetylation and repression of c-Myc 
transcription. Consistent with this, ablation of p300, YY1 or HDAC3 expression 
results in chromatin acetylation and induction of c-Myc. These three proteins 
exist as a complex in vivo and form a multiprotein complex with the YY1-binding 
site in vitro. The C-terminal region of p300 is both necessary and sufficient 
for the repression of c-Myc. These and other results suggest that in quiescent 
cells the C-terminal region of p300 provides corepressor function and 
facilitates the recruitment of p300 and HDAC3 to the YY1-binding site and 
represses the c-Myc promoter. This corepressor function of p300 prevents the 
inappropriate induction of c-Myc and S phase.