Sequence-dependent activity and compartmentalization of foreign DNA in a eukaryotic nucleus
2025
Meneu, Léa | Chapard, Christophe | Serizay, Jacques | Westbrook, Alex | Routhier, Etienne | Ruault, Myriam | Perrot, Manon | Minakakis, Alexandros | Girard, Fabien | Bignaud, Amaury | Even, Antoine | Gourgues, Géraldine | Libri, Domenico | Lartigue, Carole | Piazza, Aurèle | Thierry, Agnès | Taddei, Angela | Beckouët, Frédéric | Mozziconacci, Julien | Koszul, Romain | Régulation spatiale des Génomes - Spatial Regulation of Genomes ; Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité) | Collège Doctoral ; Sorbonne Université (SU) | Structure et Instabilité des Génomes (STRING) ; Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) | Laboratoire de Physique Théorique de la Matière Condensée (LPTMC) ; Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) | Dynamique du noyau [Institut Curie] ; Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) | Institut de Génétique Moléculaire de Montpellier (IGMM) ; Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM) | Biologie du fruit et pathologie (BFP) ; Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Unité de biologie Moléculaire, Cellulaire et du Développement (MCD) ; Centre de Biologie Intégrative (CBI) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS) | Acquisition et Analyse de Données pour l'Histoire naturelle (2AD) ; Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS) | This work was supported by the European Research Council under the Horizon 2020 Program (ERC grant agreement 771813) and Agence Nationale pour la Recherche (ANR-19-CE13-0027-02) to R.K. R.K., F.B., J.M., and An. T. also received support from Agence Nationale pour la Recherche (ANR-22-CE12-0013-01). D.L. received support from ANR (ANR-21-CE12-0040). A.M. is supported by an FRM fellowship. C.C. was supported by a Pasteur-Roux-Cantarini fellowship. J.S. was supported by an ARC fellowship. Biomics Platform, C2RT, Institut Pasteur, Paris, France, is supported by France Génomique (ANR-10-INBS-09-09) and IBISA for processing and sequencing RNA samples. | We are grateful to M. Lanzer (Heidelberg University) and C. Sanchez for providing us with P. falciparum YACs, and to S. Baumgarten for long-read sequencing of these YACs. We also thank B. Dujon, M. Fromont-Racine, A. Jacquier, G. Liti, B. Llorente, M. Nollmann, C. Saveanu, B. le Tallec, and all members of the laboratory Régulation Spatiale des Génomes for fruitful comments on the work and the manuscript. We thank C. Matthey-Doret and G. Mercy for help during the earlier steps of the project, and E. Turc and L. Lemée from the Institut Pasteur Biomics Platform; the PICT-IBiSA Imaging Facility of the Institut Curie, a member of the France Bioimaging National Infrastructure (ANR-10-INBS-04), and particularly M. Garnier for his help with FISH quantification. Strains RSG_Y711, RSG_Y681, and RSG_Y1392 (and derivatives) are available from C. Lartigue under a material transfer agreement with the INRAE. | ANR-19-CE13-0027,AN2R,Amplification des centrioles: Nature, conséquences et acteurs moléculaires impliqués dans les réarrangements chromosomique et cytoplasmique(2019) | ANR-22-CE12-0013,Dessynle,Décryptage des déterminants permettant le repliement du génome sous l'action de la cohésine(2022) | ANR-21-CE12-0040,GenoDist,Distanciation Génomique chez la levure(2021) | ANR-10-INBS-0009,France Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010) | ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010) | European Project: 771813,ERC-2017-COG,SynarchiC(2018)
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Mostrar más [+] Menos [-]Inglés. In eukaryotes, DNA-associated protein complexes coevolve with genomic sequences to orchestrate chromatin folding. We investigate the relationship between DNA sequence and the spontaneous loading and activity of chromatin components in the absence of coevolution. Using bacterial genomes integrated into Saccharomyces cerevisiae , which diverged from yeast more than 2 billion years ago, we show that nucleosomes, cohesins, and associated transcriptional machinery can lead to the formation of two different chromatin archetypes, one transcribed and the other silent, independently of heterochromatin formation. These two archetypes also form on eukaryotic exogenous sequences, depend on sequence composition, and can be predicted using neural networks trained on the native genome. They do not mix in the nucleus, leading to a bipartite nuclear compartmentalization, reminiscent of the organization of vertebrate nuclei.
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