H3.3 deposition counteracts the replication-dependent enrichment of H3.1 at chromocenters in embryonic stem cells

Abstract Chromocenters in mouse cells are membrane-less nuclear compartments representing typical heterochromatin stably maintained during cell cycle. We explore how histone H3 variants, replicative H3.1/2 or replacement H3.3, mark these domains during the cell cycle in mouse embryonic stem cells, n...

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Main Authors: S. Arfè, T. Karagyozova, A. Forest, D. Bingham, H. Hmidan, D. Mazaud, M. Garnier, P. Le Baccon, E. Meshorer, J.-P. Quivy, G. Almouzni
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60430-z
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author S. Arfè
T. Karagyozova
A. Forest
D. Bingham
H. Hmidan
D. Mazaud
M. Garnier
P. Le Baccon
E. Meshorer
J.-P. Quivy
G. Almouzni
author_facet S. Arfè
T. Karagyozova
A. Forest
D. Bingham
H. Hmidan
D. Mazaud
M. Garnier
P. Le Baccon
E. Meshorer
J.-P. Quivy
G. Almouzni
author_sort S. Arfè
collection DOAJ
description Abstract Chromocenters in mouse cells are membrane-less nuclear compartments representing typical heterochromatin stably maintained during cell cycle. We explore how histone H3 variants, replicative H3.1/2 or replacement H3.3, mark these domains during the cell cycle in mouse embryonic stem cells, neuronal precursor cells as well as immortalized 3T3 cells. We find a strong and distinct H3.1 enrichment at chromocenters, with variation in mouse embryonic stem cells. Mechanistically, this H3.1 selective enrichment depends on the DNA Synthesis Coupled deposition pathway operating in S phase challenged when we target H3.3 deposition through the DNA Synthesis Independent deposition pathway mediated by HIRA. Altering the H3.1/H3.3 dynamics at chromocenters in mouse embryonic stem cells affects nuclear morphology and cell division. Here, we reveal opposing mechanisms for H3.1 and H3.3 deposition with different enforcement according to cell cycle and potency which determine their ratio at chromocenters and are critical for genome stability and cell survival.
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issn 2041-1723
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spelling doaj-art-35910b2a5fa54e9b82b90fd8a337f74f2025-08-20T03:10:34ZengNature PortfolioNature Communications2041-17232025-06-0116111610.1038/s41467-025-60430-zH3.3 deposition counteracts the replication-dependent enrichment of H3.1 at chromocenters in embryonic stem cellsS. Arfè0T. Karagyozova1A. Forest2D. Bingham3H. Hmidan4D. Mazaud5M. Garnier6P. Le Baccon7E. Meshorer8J.-P. Quivy9G. Almouzni10Nuclear Dynamics, Institut Curie, PSL University, Sorbonne Université, CNRSNuclear Dynamics, Institut Curie, PSL University, Sorbonne Université, CNRSNuclear Dynamics, Institut Curie, PSL University, Sorbonne Université, CNRSNuclear Dynamics, Institut Curie, PSL University, Sorbonne Université, CNRSNuclear Dynamics, Institut Curie, PSL University, Sorbonne Université, CNRSNuclear Dynamics, Institut Curie, PSL University, Sorbonne Université, CNRSNuclear Dynamics, Institut Curie, PSL University, Sorbonne Université, CNRSNuclear Dynamics, Institut Curie, PSL University, Sorbonne Université, CNRSDepartment of Genetics, The Alexander Silberman Institute for Life Science, and the Edmond and Lily Safra Center for Brain Sciences (ELSC), The Hebrew University of JerusalemNuclear Dynamics, Institut Curie, PSL University, Sorbonne Université, CNRSNuclear Dynamics, Institut Curie, PSL University, Sorbonne Université, CNRSAbstract Chromocenters in mouse cells are membrane-less nuclear compartments representing typical heterochromatin stably maintained during cell cycle. We explore how histone H3 variants, replicative H3.1/2 or replacement H3.3, mark these domains during the cell cycle in mouse embryonic stem cells, neuronal precursor cells as well as immortalized 3T3 cells. We find a strong and distinct H3.1 enrichment at chromocenters, with variation in mouse embryonic stem cells. Mechanistically, this H3.1 selective enrichment depends on the DNA Synthesis Coupled deposition pathway operating in S phase challenged when we target H3.3 deposition through the DNA Synthesis Independent deposition pathway mediated by HIRA. Altering the H3.1/H3.3 dynamics at chromocenters in mouse embryonic stem cells affects nuclear morphology and cell division. Here, we reveal opposing mechanisms for H3.1 and H3.3 deposition with different enforcement according to cell cycle and potency which determine their ratio at chromocenters and are critical for genome stability and cell survival.https://doi.org/10.1038/s41467-025-60430-z
spellingShingle S. Arfè
T. Karagyozova
A. Forest
D. Bingham
H. Hmidan
D. Mazaud
M. Garnier
P. Le Baccon
E. Meshorer
J.-P. Quivy
G. Almouzni
H3.3 deposition counteracts the replication-dependent enrichment of H3.1 at chromocenters in embryonic stem cells
Nature Communications
title H3.3 deposition counteracts the replication-dependent enrichment of H3.1 at chromocenters in embryonic stem cells
title_full H3.3 deposition counteracts the replication-dependent enrichment of H3.1 at chromocenters in embryonic stem cells
title_fullStr H3.3 deposition counteracts the replication-dependent enrichment of H3.1 at chromocenters in embryonic stem cells
title_full_unstemmed H3.3 deposition counteracts the replication-dependent enrichment of H3.1 at chromocenters in embryonic stem cells
title_short H3.3 deposition counteracts the replication-dependent enrichment of H3.1 at chromocenters in embryonic stem cells
title_sort h3 3 deposition counteracts the replication dependent enrichment of h3 1 at chromocenters in embryonic stem cells
url https://doi.org/10.1038/s41467-025-60430-z
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