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.在真核生物中，DNA结合蛋白复合物会与基因组序列协同进化，以调控染色质折叠。本研究在无协同进化的条件下，探究了DNA序列与染色质组分自发装载及活性之间的关联。我们采用整合至酿酒酵母（Saccharomyces cerevisiae）的细菌基因组开展实验——该物种与酵母的分化时间距今达15亿年——结果表明，核小体（nucleosomes）、黏连蛋白复合物（cohesins）与转录机器（transcriptional machinery）可在不依赖异染色质形成的前提下，催生两种截然不同的染色质原型：一类为转录活跃型，另一类为沉默型。这两类染色质原型同样可在真核生物外源序列上形成，其形成依赖于序列组成，且可通过基于内源基因组训练的神经网络进行预测。两类原型在细胞核内互不混合，由此形成二分核区室化结构，其组织模式与脊椎动物细胞核的组织结构颇为相似。