TRANSCRIPTIONAL ACTIVATORS DIRECT HISTONE ACETYLTRANSFERASE COMPLEXESTO NUCLEOSOMES

Transcriptional co-activators were originally identified as proteins t hat act as intermediaries between upstream activators and the basal tr anscription machinery. The discovery that co-activators such as Tetrah ymena and yeast Gcn5( >)(1,2), as well as human p300/CBP3,4, pCAF(5), Src-1(6), ACTR(7) and TAFII250(8), can acetylate histones suggests tha t activators may be involved in targeting acetylation activity to prom oters. Several histone deacetylases have been linked to transcriptiona l co-repressor proteins(9), suggesting that the action of both acetyla ses and deacetylases is important in the regulation of many genes. Her e we demonstrate the binding of two native yeast histone acetyltransfe rase (HAT) complexes to the herpesvirus VP16 activation domain and the yeast transcriptional activator Gcn4 and show that it is their intera ction with the VP16 activation domain that targets Gal4-VP16-bound nuc leosomes for acetylation. We find that Gal4-VP16-driven transcription from chromatin templates is stimulated by both HAT complexes in an ace tyl CoA-dependent reaction. Our results demonstrate the targeting of n ative HAT complexes by a transcription-activation domain to nucleosome s in order to activate transcription.