An archaeal chromatin protein condenses DNA through bridging-induced phase separation

Abstract Phase separation serves an important role in the three-dimensional chromosome organization and remodeling in eukaryotes. Whether this process is involved in archaeal chromosome organization is unknown. Here we demonstrate that archaeal DNA condensing protein1 (aDCP1) from the hyperthermophilic crenarchaeon Sulfolobus islandicus is able to bridge DNA efficiently and form large protein-DNA condensates with a droplet- or gel-like morphology in vitro. Within the condensates, aDCP1 exhibits a fast dynamic while the DNA appears in a solid-like state. At the single-molecule level, aDCP1 efficiently compacts DNA through a three-step mechanism, which presumably entails the clustering of aDCP1 on the DNA and the subsequent fusion of the clusters. Deletion of the aDCP1 gene results in noticeable changes in chromosome conformation in S. islandicus, which are characterized by enhanced interactions between the A and B compartments and reduced interactions within the self-interacting domains as well as between domains in the same compartment. Taken together, our results indicate that aDCP1 is capable of inducing DNA bridging-induced phase separation and serves a role in chromosome organization in the organism.