UMR168 – Laboratoire Physico-Chimie Curie

Publications de l’UMR 168

Année de publication : 2018

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 (2018 Aug 9)

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

Nature communications : 9 : DOI : 10.1038/s41467-018-05697-1 En savoir plus
Résumé

DNA replication is a challenge for the faithful transmission of parental information to daughter cells, as both DNA and chromatin organization must be duplicated. Replication stress further complicates the safeguard of epigenome integrity. Here, we investigate the transmission of the histone variants H3.3 and H3.1 during replication. We follow their distribution relative to replication timing, first in the genome and, second, in 3D using super-resolution microscopy. We find that H3.3 and H3.1 mark early- and late-replicating chromatin, respectively. In the nucleus, H3.3 forms domains, which decrease in density throughout replication, while H3.1 domains increase in density. Hydroxyurea impairs local recycling of parental histones at replication sites. Similarly, depleting the histone chaperone ASF1 affects recycling, leading to an impaired histone variant landscape. We discuss how faithful transmission of histone variants involves ASF1 and can be impacted by replication stress, with ensuing consequences for cell fate and tumorigenesis.

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Merle T, Farge E. (2018 Aug 1)

Trans-scale mechanotransductive cascade of biochemical and biomechanical patterning in embryonic development: the light side of the force.

Curr. Opin. Cell. Biol. : DOI : 10.1016/j.ceb.2018.07.003 En savoir plus
Résumé

Embryonic development is made of complex tissue shape changes and cell differentiation tissue patterning. Both types of morphogenetic processes, respectively biomechanical and biochemical in nature, were historically long considered as disconnected. Evidences of the biochemical patterning control of morphogenesis accumulated during the last 3 decades. Recently, new data revealed reversal mechanotransductive feedback demonstrating the strong coupling between embryonic biomechanical and biochemical patterning. Here we will review the findings of the emerging field of mechanotransduction in animal developmental biology and its most recent advancements. We will see how such mechanotransductive cascade of biochemical and mechanical patterning events ensures trans-scale direct cues of co-regulation of the microscopic biomolecular activities with the macroscopic morphological patterning. Mechanotransduction regulates many aspects of embryonic development including efficient collective cell behaviour, distant tissues morphogenesis coordination, and the robust coordination of tissue shape morphogenesis with differentiation.

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Simon C, Caorsi V, Campillo C, Sykes C (2018 Jul 30)

Interplay between membrane tension and the actin cytoskeleton determines shape changes

Physical Biology : 5 : 065004 : DOI : 10.1088/1478-3975/aad1ab En savoir plus
Résumé

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Röper Jens-Christian, Mitrossilis Démosthène, Stirnemann Guillaume, Waharte François, Brito Isabel, Fernandez-Sanchez Maria-Elena, Baaden Marc, Salamero Jean, Farge Emmanuel (2018 Jul 19)

The major β-catenin/E-cadherin junctional binding site is a primary molecular mechano-transductor of differentiation in vivo

eLIFE : 7:e33381. DOI: https://doi.org/10.7554/eLife.33381 : DOI : DOI: https://doi.org/10.7554/eLife.33381 En savoir plus
Résumé

In vivo, the primary molecular mechanotransductive events mechanically initiating cell differentiation remain unknown. Here we find the molecular stretching of the highly conserved Y654-beta-catenin-D665-E-cadherin binding site as mechanically induced by tissue strain. It triggers the increase of accessibility of the Y654 site, target of the Src42A kinase phosphorylation leading to irreversible unbinding. Molecular dynamics simulations of the beta-catenin/E-cadherin complex under a force mimicking a 6 pN physiological mechanical strain predict a local 45% stretching between the two a-helices linked by the site and a 15% increase in accessibility of the phosphorylation site. Both are quantitatively observed using FRET lifetime imaging and non-phospho Y654 specific antibody labelling, in response to the mechanical strains developed by endogenous and magnetically mimicked early mesoderm invagination of gastrulating Drosophila embryos. This is followed by the predicted release of 16% of beta-catenin from junctions, observed in FRAP, which initiates the mechanical activation of the b-catenin pathway process.

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