Regulation of Histone Acetylation and Transcription by INHAT, a Human Cellular Complex Containing the Set Oncoprotein

Acetylation of histones by p300/CBP and PCAF is considered to be a critical step in transcriptional regulation. In order to understand the role of cellular activities that modulate histone acetylation and transcription, we have purified and characterized a multiprotein cellular complex that potently inhibits the histone acetyltransferase activity of p300/CBP and PCAF. We have mapped a novel acetyltransferase-inhibitory domain of this INHAT ( inh ibitor of a cetyl t ransferases) complex that binds to histones and masks them from being acetyltransferase substrates. Endogenous INHAT subunits, which include the Set/TAF-I β oncoprotein, associate with chromatin in vivo and can block coactivatormediated transcription when transfected in cells. We propose that histone masking by INHAT plays a regulatory role in chromatin modification and serves as a novel mechanism of transcriptional regulation.