Arfè S, Karagyozova T, Forest A, Bingham D, Hmidan H, Mazaud D, Garnier M, Le Baccon P, Meshorer E, Quivy J-P, Almouzni G
Nuclear Dynamics, Institut Curie, PSL University, Sorbonne Université, CNRS, Paris, France.
Center for Neural Science and Medicine, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Nat Commun. 2025 Jun 3;16(1):5138. doi: 10.1038/s41467-025-60430-z.
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.
小鼠细胞中的染色体中心是无膜核区室，代表着在细胞周期中稳定维持的典型异染色质。我们探究了组蛋白H3变体，即复制型H3.1/2或替代型H3.3，在小鼠胚胎干细胞、神经前体细胞以及永生化3T3细胞的细胞周期中如何标记这些区域。我们发现染色体中心有强烈且明显的H3.1富集，在小鼠胚胎干细胞中存在差异。从机制上讲，这种H3.1选择性富集取决于在S期起作用的DNA合成偶联沉积途径，当我们通过由HIRA介导的DNA合成非依赖性沉积途径靶向H3.3沉积时，该途径受到挑战。改变小鼠胚胎干细胞染色体中心的H3.1/H3.3动态会影响核形态和细胞分裂。在这里，我们揭示了H3.1和H3.3沉积的相反机制，根据细胞周期和潜能有不同的作用强度，这决定了它们在染色体中心的比例，对基因组稳定性和细胞存活至关重要。
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