The Structural Basis for Specific Recognition of H3K14 Acetylation by Sth1 in the RSC Chromatin Remodeling Complex

Abstract

The Saccharomyces cerevisiae RSC (Remodel the Structure of Chromatin) complex is a chromatin-remodeling complex and plays essential roles in transcription regulation and DNA repair. The acetylation of H3 Lysine14 (H3K14Ac) enhances the RSC retention on nucleosomes and increases the remodeling activity of RSC. However, which RSC component recognizes H3K14Ac remains unclear. Here, we discovered that the bromodomain of the catalytic subunit Sth1 (Sth1BD) possessed the strongest affinity to H3K14Ac among all RSC bromodomains. The Sth1BD specifically recognized the K(Ac)ΦΦR motif (Φ stands for any hydrophobic amino acid), including H3K14Ac and H4K20Ac. We determined the crystal structures of Sth1BD at 2.40Å resolution and Sth1BD-H3K14Ac complex at 1.40Å resolution. The extensive interfaces between Sth1BD and H36-21 facilitate the specific and robust binding of Sth1BD to H3K14Ac. Our studies provide insights into how the RSC complex recognizes H3K14Ac to orchestrate the crosstalk between histone acetylation and chromatin remodeling.