Journal
NUCLEIC ACIDS RESEARCH
Volume 44, Issue 1, Pages 472-484Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkv1321
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Funding
- NIH [GM100907, GM106416, GM083055, T32AA007464]
- CIHR [MOP-64289]
- Canada Research Chair in Chromatin Biology and Molecular Epigenetics
- American Heart Association
- Grants-in-Aid for Scientific Research [25116002, 26890023] Funding Source: KAKEN
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BRPF1 (bromodomain PHD finger 1) is a core subunit of the MOZ histone acetyltransferase (HAT) complex, critical for normal developmental programs and implicated in acute leukemias. BRPF1 contains a unique assembly of zinc fingers, termed a PZP domain, the physiological role of which remains unclear. Here, we elucidate the structure-function relationship of this novel epigenetic reader and detail the biological and mechanistic consequences of its interaction with nucleosomes. PZP has a globular architecture and forms a 2: 1 stoichiometry complex with the nucleosome, bivalently interacting with histone H3 and DNA. This binding impacts the nucleosome dynamics, shifting the DNA unwrapping/rewrapping equilibrium toward the unwrapped state and increasing DNA accessibility. We demonstrate that the DNA-binding function of the BRPF1 PZP domain is required for the MOZ-BRPF1-ING5-hEaf6 HAT complex to be recruited to chromatin and to acetylate nucleosomal histones. Our findings reveal a novel link between chromatin dynamics and MOZ-mediated acetylation.
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