Activation domain-specific and general transcription stimulation by nativehistone acetyltransferase complexes

Recent progress in identifying the catalytic subunits of histone acetyltran sferase (HAT) complexes has implicated histone acetylation in the regulatio n of transcription. Here, we have analyzed the function of two native yeast HAT complexes, SAGA (Spt-Ada-Gcn5 Acetyltransferase) and NuA4 (nucleosome acetyltransferase of H4), in activating transcription from preassembled nuc leosomal array templates in vitro. Each complex was tested for the ability to enhance transcription driven by GAL4 derivatives containing either acidi c, glutamine-rich, or proline-rich activation domains. On nucleosomal array templates, the SAGA complex selectively stimulates transcription driven by the VP16 acidic activation domain in an acetyl coenzyme A-dependent manner . In contrast, the NuA4 complex facilitates transcription mediated by any o f the activation domains tested if allowed to preacetylate the nucleosomal template, indicating a general stimulatory effect of histone H4 acetylation . However, when the extent of acetylation by NuA4 is limited, the complex a lso preferentially stimulates VP16-driven transcription. SAGA and NuA4 inte ract directly with the VP16 activation domain but not with a glutamine-rich or proline-rich activation domain. These data suggest that recruitment of the SAGA and NuA4 HAT complexes by the VP16 activation domain contributes t o HAT-dependent activation. In addition, extensive H4/H2B acetylation by Nu A4 leads to a general activation of transcription, which is independent of activator-NuA4 interactions.