Genome-wide replication-independent histone H3 exchange occurs predominantly at promoters and implicates H3 K56 acetylation and Asf1.

In yeast, histone H3/H4 exchange independent of replication is poorly understood. Here, we analyzed the deposition of histone H3 molecules, synthesized during G1, using a high-density microarray histone exchange assay. While we found that H3 exchange in coding regions requires high levels of transcription, promoters exchange H3 molecules in the absence of transcription. In inactive promoters, H3 is deposited predominantly in well-positioned nucleosomes surrounding nucleosome-free regions, indicating that some nucleosomes in promoters are dynamic. This could facilitate induction of repressed genes. Importantly, we show that histone H3 K56 acetylation, a replication-associated mark, is also present in replication-independent newly assembled nucleosomes and correlates perfectly with the deposition of new H3. Finally, we found that transcription-dependent incorporation of H3 at promoters is highly dependent on Asf1. Taken together, our data underline the dynamic nature of replication-independent nucleosome assembly/disassembly, specify a link to transcription, and implicate Asf1 and H3 K56 acetylation.