The histone deacetylase HDAC3 targets RbAp48 to the retinoblastoma protein

The product of the retinoblastoma susceptibility gene, the Rb protein, func tions partly through transcriptional repression of E2F-regulated genes. Rep ression by Rb is mediated, at least in part, by a histone deacetylase compl ex, whose enzymatic activity relies on HDAC1, HDAC2 or HDAC3. Recently, we have shown that the Rb-associated histone deacetylase complex contains RbAp 48 protein, which interacts with HDAC1 and HDAC2. RbAp48 could favour the d eacetylation of histones since it binds directly to histone H4. In agreemen t with that, we show that transcriptional repression of E2F activity requir es the presence of RbAp48. HDAC3 was thought not to interact with RbAp48. H owever, we found that it shared with HDAC1 the ability to favour the recrui tment of RbAp48 to Rb. This latter effect was unlikely to be due to activat ion of Rb function, since HDAC3 did not increase Rb-E2F1 interaction. Rathe r, we found, surprisingly, that HDAC3 could physically interact with RbAp48 both in vitro and in living cells. Taken together, our data suggest a mode l in which Rb mediates the recruitment to E2F-regulating promoters of a rep ressive complex containing either HDAC1, HDAC2 or HDAC3 and the histone-bin ding protein RbAp48.