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

Molecular Basis for the PZP Domain of BRPF1 Association with Chromatin.

Author information

1
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
2
Department of Physics, Ohio State University, Columbus, OH 43210, USA.
3
Laval University Cancer Research Center, CHU de Québec-UL Research Center-Oncology Division, Quebec City, QC G1R 3S3, Canada.
4
Department of Physics, Ohio State University, Columbus, OH 43210, USA. Electronic address: poirier.18@osu.edu.
5
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: tatiana.kutateladze@cuanschutz.edu.

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

PMID:
31711755
PMCID:
PMC6949404
[Available on 2021-01-07]
DOI:
10.1016/j.str.2019.10.014

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