Sequence-dependent activity and compartmentalization of foreign DNA in a eukaryotic nucleus [ChIP-Seq]

In eukaryotes, DNA-associated protein complexes co-evolve with genomic sequence to orchestrate chromatin folding into functional chromosomes. Here, we investigate the relationship between DNA sequence and the spontaneous loading and activity of chromatin components in the absence of co-evolutions. Using bacterial genomes integrated into S. cerevisiae, which diverged from yeast up to 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 being transcribed and the other silent. These two archetypes also form on eukaryotic exogenous sequences, and depend on sequence composition. They do not mix in the nucleus, leading to a bipartite nuclear compartmentalisation reminiscent of the organization of vertebrate nuclei. Our findings represent a significant advance in understanding the primary molecular mechanisms that govern the co-option or silencing of DNA sequences integrated into foreign genomes during natural horizontal gene transfers, or in synthetic genomics projects. We explored whether nucleosomes were able to form on bacterial chromosomes integrated in a eukaryotic environment by performing MNase-seq analysis of yeast strains containing linearized and telomerized bacterial chromosomes.