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High-resolution visualization of H3 variants during replication reveals their controlled recycling

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Geneviève Almouzni’s Team dedicates its last publication in Nature Communications to Maxime Dahan, Director of the Curie Physical Chemistry Unit, who passed away suddenly on Saturday, July 28 at the age of 46. This work focuses on chromatin replication, a challenging mechanism for the faithful transmission of parental information to daughter cells, as both DNA and chromatin organization must be replicated.

Replication stress at the level of chromatin further complicates the safeguard of epigenome integrity. Camille Clément, Guillaume Orsi and Jean-Pierre Quivy from Chromatin dynamics’ team (Institut Curie/CNRS/PSL/Sorbonne université) focus on the transmission of histone variants H3.3 and H3.1 during replication. They follow their distribution relative to replication timing, first in the genome and, second, in 3D using super-resolution microscopy. They find that H3.3 and H3.1 mark early- and late-replicating chromatin, respectively. In nucleus, H3.3 forms domains, which decrease in density throughout replication, while H3.1 domains increase in density. Hydroxyurea, a replication inhibitor, impairs local recycling of parental histones at replication sites. Similarly, depleting the histone chaperone ASF1 affects recycling, leading to an impaired histone variant landscape. The researchers also discuss replication stress, with ensuing consequences for cell fate and tumorigenesis.

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High-resolution visualization of H3 variants during replication reveals their controlled recycling 
Camille Clément, Guillermo A. Orsi, Alberto Gatto, Ekaterina Boyarchuk, Audrey Forest, Bassam Hajj, Judith Miné-Hattab, Mickaël Garnier, Zachary A. Gurard-Levin, Jean-Pierre Quivy & Geneviève Almouzni

Nature communications, 9, Article number: 3181 (2018)