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

In eukaryotes, DNA-associated protein complexes co-evolve with genomic sequence to orchestrate chromatin folding. Here, we investigate the relationship between DNA sequence and the spontaneous loading and activity of chromatin components in the absence of co-evolution. Using bacterial genomes integrated into S. cerevisiae, which diverged from yeast 1.5 billion years ago, we show that nucleosomes, cohesins and the 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.