ACETYLATION OF HMG I(Y) BY CBP TURNS OFF IFN-BETA EXPRESSION BY DISRUPTING THE ENHANCEOSOME

The transcriptional coactivators CBP and P/CAF are required for activa tion of transcription from the IFN beta enhanceosome. We show that CBP and P/CAF acetylate HMG I(Y), the essential architectural component r equired for enhanceosome assembly, at distinct lysine residues, causin g distinct effects on transcription. Thus, in the context of the enhan ceosome, acetylation of HMG I by CBP, but not by P/CAF, leads to enhan ceosome destabilization and disassembly. We demonstrate that acetylati on of HMG I(Y) by CBP is essential for turning off IFN beta gene expre ssion. Finally, we show that the acetyltransferase activities of CBP a nd P/CAF modulate both the strength of the transcriptional response an d the kinetics of virus-dependent activation of the IFN beta gene.