Crosstalk between epigenetic readers regulates the MOZ/MORF HAT complexes

Abstract

The MOZ/MORF complexes represent an example of a chromatin-binding assembly whose recruitment to specific genomic regions and activity can be fine-tuned by posttranslational modifications of histones. Here we detail the structures and biological functions of epigenetic readers present in the four core subunits of the MOZ/MORF complexes, highlight the imperative role of combinatorial readout by the multiple readers, and discuss new research directions to advance our understanding of histone acetylation.

Keywords: BRPF; ING5; KAT6A; KAT6B; MORF; MOZ; PHD; acetylation; histone; reader.

Figure 1. The MOZ/MORF composition. (A) The 4 core subunits of the MOZ/MORF complexes are shown. (B) The readers, a writer, and DNA-binding domains identified in each subunit of the MOZ/MORF complexes are colored and labeled.

Figure 2. The structural basis for ligand binding by KAT6A/B. (A) The KAT6A/B domain architecture. (B) The crystal structure of the KAT6A MYST domain in complex with Ac-CoA (PDB: 2RC4). (C) The crystal structure of the double PHD finger (DPF) of KAT6A in complex with H3K14ac peptide (PDB: 3V43).

Figure 3. The structural basis for ligand binding by BRPF1/2. (A) The BRPF1/2/3 domain architecture. (B) The solution structure of the unmodified H3-bound PHD1 finger of BRPF2 (PDB: 2L43). (C) The solution structure and electrostatic potential surface of the PHD2 finger of BRPF2 in the apo-state (PDB: 2LQ6). (D) The NMR structure of the H4K5ac-bound BD of BRPF1 (PDB: 2RS9). (E) The crystal structure of the PWWP domain of BRPF1 in complex with H3K36me3 peptide (PDB: 2X4W).

Figure 4. The structural basis for ligand binding by ING5. (A) The ING5 domain architecture. (B) The crystal structure of the H3K4me3-ING5 PHD finger complex (PDB: 3C6W). (C) The hEAF6 domain architecture.