Sequence-dependent activity and compartmentalization of foreign DNA in a eukaryotic nucleus

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 <i>Saccharomyces cerevisiae</i>, 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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Publication Details

Journal
Science
Published
2025-02-06
DOI
https://doi.org/10.1126/science.adm9466
Citations
24
Primary Topic
Genomics and Chromatin Dynamics
Type
article
Field-Weighted Citation Impact
19.34
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article

Sequence-dependent activity and compartmentalization of foreign DNA in a eukaryotic nucleus

Fabien Girard, Etienne Routhier, Julien Mozziconacci, Angela Taddei et al.
24 citations
Science
Genomics and Chromatin Dynamics
19.34
article

Sequence-dependent activity and compartmentalization of foreign DNA in a eukaryotic nucleus

Fabien Girard, Etienne Routhier, Julien Mozziconacci, Angela Taddei, Romain Koszul, Domenico Libri, Frédéric Beckouët, Aurèle Piazza, Jacques Serizay, Léa Meneu, Manon Perrot, Carole Lartigue, Christophe Chapard, Antoine Even, Amaury Bignaud, Agnès Thierry, Myriam Ruault, Géraldine Gourgues, Alex Westbrook, Alexandros Minakakis
article en
24 citations

Abstract

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 <i>Saccharomyces cerevisiae</i>, 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.

ScienceVol. 387(6734)
Centre National de la Recherche Scientifique (FR), Université Toulouse III - Paul Sabatier (FR), Université de Bordeaux (FR), Institut Pasteur (FR), Université de Montpellier (FR), Université Paris Cité (FR), Université Paris Sciences et Lettres (FR), Sorbonne Université (FR), Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR), Biologie du Fruit et Pathologie (FR), Centre de Biologie du Développement (FR), Institut de Génétique Moléculaire de Montpellier (FR), Muséum national d'Histoire naturelle (FR), Laboratoire de Physique Théorique de la Matière Condensée (FR), Dynamique du noyau (FR), Structure et Instabilité des Génomes (FR)
Life in Land
Openalex Percentile: Top 0%
Genomics and Chromatin Dynamics
19.34
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