Sequence-dependent activity and compartmentalization of foreign DNA in a eukaryotic nucleus [Hi-C]

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.在真核生物中，DNA结合蛋白复合物与基因组序列协同进化，以调控染色质折叠为功能性染色体。本研究旨在探究无共进化背景下，DNA序列与染色质组分自发加载及活性之间的关联。我们采用整合至酿酒酵母（Saccharomyces cerevisiae，通常缩写为S. cerevisiae）中的细菌基因组开展实验，该类细菌基因组的来源物种与酿酒酵母的分化时间可达15亿年。实验结果显示，核小体、黏连蛋白与转录机器可介导两种截然不同的染色质原型的形成：其一为转录活性型，其二为沉默型。这两种染色质原型同样可在真核外源性序列上形成，且其形成依赖于序列组成。二者在细胞核内互不混合，形成二元核区室化结构，该结构与脊椎动物细胞核的组织模式高度相似。本研究的发现为理解自然水平基因转移或合成基因组学项目中，整合进入异源基因组的DNA序列的共招募或沉默所依赖的核心分子机制，提供了重要进展。