The histone chaperone ANP32B regulates chromatin incorporation of the atypical human histone variant macroH2A.

Autor:	Mandemaker IK; Biomedical Center (BMC), Department of Physiological Chemistry, Faculty of Medicine, LMU Munich, 82152 Planegg-Martinsried, Germany; Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, the Netherlands. Electronic address: i.mandemaker@hubrecht.eu., Fessler E; Gene Center and Department of Biochemistry, LMU Munich, 81377 Munich, Germany., Corujo D; Applied Epigenetics Program, Myeloid Neoplasm Program, Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-GTP-UAB, 08916 Badalona, Barcelona, Spain; Germans Trias I Pujol Research Institute (IGTP), 08916 Badalona, Barcelona, Spain., Kotthoff C; Biomedical Center (BMC), Department of Physiological Chemistry, Faculty of Medicine, LMU Munich, 82152 Planegg-Martinsried, Germany., Wegerer A; Biomedical Center (BMC), Department of Physiological Chemistry, Faculty of Medicine, LMU Munich, 82152 Planegg-Martinsried, Germany., Rouillon C; Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, the Netherlands., Buschbeck M; Applied Epigenetics Program, Myeloid Neoplasm Program, Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-GTP-UAB, 08916 Badalona, Barcelona, Spain; Germans Trias I Pujol Research Institute (IGTP), 08916 Badalona, Barcelona, Spain., Jae LT; Gene Center and Department of Biochemistry, LMU Munich, 81377 Munich, Germany., Mattiroli F; Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, the Netherlands. Electronic address: f.mattiroli@hubrecht.eu., Ladurner AG; Biomedical Center (BMC), Department of Physiological Chemistry, Faculty of Medicine, LMU Munich, 82152 Planegg-Martinsried, Germany; Eisbach Bio GmbH, 82152 Planegg-Martinsried, Germany. Electronic address: andreas.ladurner@bmc.med.lmu.de.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Oct 31; Vol. 42 (10), pp. 113300. Date of Electronic Publication: 2023 Oct 19.
DOI:	10.1016/j.celrep.2023.113300
Abstrakt:	All vertebrate genomes encode for three large histone H2A variants that have an additional metabolite-binding globular macrodomain module, macroH2A. MacroH2A variants impact heterochromatin organization and transcription regulation and establish a barrier for cellular reprogramming. However, the mechanisms of how macroH2A is incorporated into chromatin and the identity of any chaperones required for histone deposition remain elusive. Here, we develop a split-GFP-based assay for chromatin incorporation and use it to conduct a genome-wide mutagenesis screen in haploid human cells to identify proteins that regulate macroH2A dynamics. We show that the histone chaperone ANP32B is a regulator of macroH2A deposition. ANP32B associates with macroH2A in cells and in vitro binds to histones with low nanomolar affinity. In vitro nucleosome assembly assays show that ANP32B stimulates deposition of macroH2A-H2B and not of H2A-H2B onto tetrasomes. In cells, depletion of ANP32B strongly affects global macroH2A chromatin incorporation, revealing ANP32B as a macroH2A histone chaperone. Competing Interests: Declaration of interests A.G.L. is a founder, CSO, and managing director of Eisbach Bio GmbH, a biotechnology company in oncology and virology. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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