Mechanistic study of molecular crosstalk between Chd1p and histone H3K36 acetylation

Abstract

Histone H3K36 modifications is known to play a pivotal role in gene transcription through Set2-mediated methylation. However, histone H3K36 residue is not only methylated but also acetylated. Acetylation of histone H3K36 is evolutionary conserved, but the role is poorly understood. Here we show the role of histone H3K36 acetylation (H3K36Ac) in chromatin regulation. We find that the chromodomain of ATP-dependent nucleosome remodeler Chd1p specifically recognizes H3K36Ac and changes of H3K36Ac pattern alters Chd1p occupancy on chromatin. In addition, nucleosome sliding activity of Chd1p is stimulated by the presence of K36-acetylated histone H3 in nucleosome in vitro. In agreement with this result, we find that the effect of chd1$\Delta$ in nucleosome positioning is most prominent at a subset of genes where H3K36Ac and Chd1p are co-enriched. Furthermore, Chd1 depletion causes defect in release of RNA Pol II properly on promoter and interestingly histone H3 binding activity of Chd1 is crucial for the activity of RNA Pol II escape. Collectively, our findings indicate that in contrast to other chromodomains that interact with methylated histone, chromodomain of Chd1p is able to bind acetylated histone maintaining proper chromatin configuration and acts on efficient RNA Pol II escape.