Multiple links between the NuA4 histone acetyltransferase complex and epigenetic control of transcription

NuA4 is an essential histone H4/H2A acetyltransferase complex that interact s with activators and stimulates transcription in vitro. We have identified three novel NuA4 subunits: Act3/Arp4, an actin-related protein implicated in epigenetic control of transcription, Act1, and EpI1, a protein homologou s to Drosophila Enhancer of Polycomb. Act3/Arp4 binds nucleosomes in vitro and is required for NuA4 integrity in vivo. Mutations in ACT3 and acetyltra nsferase-encoding ESA1 cause gene-specific transcription defects. According ly, NuA4 is localized in precise loci within the nucleus and does not overl ap with the silent chromatin marker Sir3. These data along with the known e pigenetic roles of Act3/Arp4 and homologs of EpI2 and Esa1 strongly support an essential role for chromatin structure modification by NuA4 in transcri ption regulation in vivo.