Molecular Basis for the PZP Domain of BRPF1 Association with Chromatin

Structure. 2020 Jan 7;28(1):105-110.e3. doi: 10.1016/j.str.2019.10.014. Epub 2019 Nov 8.

Abstract

The assembly of human histone acetyltransferase MOZ/MORF complexes relies on the scaffolding bromodomain plant homeodomain (PHD) finger 1 (BRPF1) subunit. The PHD-zinc-knuckle-PHD module of BRPF1 (BRPF1PZP) has been shown to associate with the histone H3 tail and DNA; however, the molecular mechanism underlying recognition of H3 and the relationship between the histone and DNA-binding activities remain unclear. In this study, we report the crystal structure of BRPF1PZP bound to the H3 tail and characterize the role of the bipartite interaction in the engagement of BRPF1PZP with the nucleosome core particle (NCP). We find that although both interactions of BRPF1PZP with the H3 tail and DNA are required for tight binding to NCP and for acetyltransferase function of the BRPF1-MORF-ING5-MEAF6 complex, binding to extranucleosomal DNA dominates. Our findings suggest that functionally active BRPF1PZP might be important in stabilization of the MOZ/MORF complexes at chromatin with accessible DNA.

Keywords: BRPF1; DNA; MORF; MOZ; PZP; chromatin; histone.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Catalytic Domain
  • Chromatin / metabolism*
  • Crystallography, X-Ray
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism*
  • Histones / metabolism
  • Humans
  • Protein Binding
  • Protein Domains

Substances

  • Adaptor Proteins, Signal Transducing
  • BRPF1 protein, human
  • Chromatin
  • DNA-Binding Proteins
  • Histones
  • DNA