Bridging-driven condensation by eukaryotic SMC complexes is a conserved feature of genome organization
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Jae-Won Jang Torahiko Higashi Tony Tang Changyeop Kim Yoshimi Kinoshita Hajin Myeong Joonyoung Lee Tomoko Nishiyama Won-Ki Cho Frank Uhlmann Cees Dekker Je-Kyung RyuAbstract
The Structural Maintenance of Chromosome (SMC) protein family plays a central role in higher-order genome organization through ATP-dependent DNA loop extrusion by cohesin and condensin and other processes. Whether these activities fully account for the complexity of chromosome architecture remains unknown. Here, we uncover a conserved ATP-independent mechanism of chromatin condensation by SMC complexes, occurring via biomolecular condensation. Using single-molecule fluorescence imaging, we show that a variety of SMCs form dynamic DNA-bound condensates that exhibit key features of biomolecular condensates, including droplet coalescence, fluorescence recovery after photobleaching, and rapid exchange with free SMC complexes. Atomic force microscopy analysis of human cohesin-DNA assemblies reveals DNA-length-dependent clustering, providing evidence for bridging-driven condensation. Analyses of in vivo super-resolution imaging and high-throughput chromosome conformation capture (Hi-C) data indicate that these condensates form chromatin-associated clusters with multi-loop structures. Together, our results establish that SMC complexes employ ATP-independent phase condensation as well as ATP-dependent activities to shape genome architecture. This work reveals a broadly conserved principle of chromosomal organization across eukaryotes.
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Journal
Nucleic Acids Research
Volume
54
Issue number
16
Pages
gkag850
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10.1093/nar/gkag850
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Europe PubMed Central
42689414
Pubmed
42689414
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