TY - JOUR
T1 - H3.3 deposition counteracts the replication-dependent enrichment of H3.1 at chromocenters in embryonic stem cells
AU - Arfè, S.
AU - Karagyozova, T.
AU - Forest, A.
AU - Bingham, D.
AU - Hmidan, H.
AU - Mazaud, D.
AU - Garnier, M.
AU - Le Baccon, P.
AU - Meshorer, E.
AU - Quivy, J. P.
AU - Almouzni, G.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=105007186721&partnerID=8YFLogxK
U2 - 10.1038/s41467-025-60430-z
DO - 10.1038/s41467-025-60430-z
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C2 - 40461574
AN - SCOPUS:105007186721
SN - 2041-1723
VL - 16
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5138
ER -