Sequence-dependent activity and compartmentalization of foreign DNA in a eukaryotic nucleus
Léa Meneu, Christophe Chapard, Jacques Serizay, Alex Westbrook, Etienne Routhier, Myriam Ruault, Manon Perrot, Alexandros Minakakis, Fabien Girard, Amaury Bignaud, Antoine Even, Géraldine Gourgues, Domenico Libri, Carole Lartigue, Aurèle Piazza, Agnès Thierry, Angela Taddei, Frédéric Beckouët, Julien Mozziconacci, Romain Koszul
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 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.