Histone variant macroH2A1 regulates synchronous firing of replication origins in the inactive X chromosome.

Autor:	Arroyo M; Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, 64287 Darmstadt, Germany., Casas-Delucchi CS; Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, 64287 Darmstadt, Germany., Pabba MK; Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, 64287 Darmstadt, Germany., Prorok P; Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, 64287 Darmstadt, Germany., Pradhan SK; Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, 64287 Darmstadt, Germany., Rausch C; Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, 64287 Darmstadt, Germany., Lehmkuhl A; Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, 64287 Darmstadt, Germany., Maiser A; Faculty of Biology and Center for Molecular Biosystems (BioSysM), Human Biology and BioImaging, LMU Munich, Munich 81377, Germany., Buschbeck M; Program of Myeloid Neoplasms, Program of Applied Epigenetics, Josep Carreras Leukaemia Research Institute (IJC), Germans Trias i Pujol Research Institute (IGTP), Campus Can Ruti, Camí de les Escoles, 08916 Badalona, Barcelona, Spain., Pasque V; Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single-Cell Omics (LISCO), KU Leuven-University of Leuven, 3000 Leuven, Belgium., Bernstein E; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, NY, NY 10029, USA., Luck K; Institute of Molecular Biology (IMB) gGmbH, 55128 Mainz, Germany., Cardoso MC; Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, 64287 Darmstadt, Germany.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 Oct 28; Vol. 52 (19), pp. 11659-11688.
DOI:	10.1093/nar/gkae734
Abstrakt:	MacroH2A has been linked to transcriptional silencing, cell identity, and is a hallmark of the inactive X chromosome (Xi). However, it remains unclear whether macroH2A plays a role in DNA replication. Using knockdown/knockout cells for each macroH2A isoform, we show that macroH2A-containing nucleosomes slow down replication progression rate in the Xi reflecting the higher nucleosome stability. Moreover, macroH2A1, but not macroH2A2, regulates the number of nano replication foci in the Xi, and macroH2A1 downregulation increases DNA loop sizes corresponding to replicons. This relates to macroH2A1 regulating replicative helicase loading during G1 by interacting with it. We mapped this interaction to a phenylalanine in macroH2A1 that is not conserved in macroH2A2 and the C-terminus of Mcm3 helicase subunit. We propose that macroH2A1 enhances the licensing of pre-replication complexes via DNA helicase interaction and loading onto the Xi. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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