포스텍 토토 분석학과 강사 초빙 공고
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2020.01.06 /3,264Links
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1. 연사: 류제경 박사 (TU Delft)
2. 일시: 2020. 1. 13(월), 오후 1시
3. 장소: 공학3동 302호 (세미나실)
4. 제목: Fundamental principles of SMC-mediated genome organization
In a living cell, 2 meter length of 토토 사이트, containing the whole genetic information of an organism, is organized into a super tiny microscale-sized cell. This tremendous compaction is mainly mediated by structural maintenance of chromosome (SMC) proteins in every living kingdom, which govern both spatial and temporal chromosome organization. However, it is still largely unknown how the SMC proteins work for the genome organization. To understand the fundamental principle how the SMC proteins organize chromosomes, we used various single-molecule tools: atomic force microscopy (AFM), magnetic tweezers, and single-molecule fluorescence assay. Firstly, we showed that a single condensin complex extrudes a 토토 사이트 loop using both single-molecule florescence assay and AFM (1, 2). Using a liquid-phase high-speed AFM microscope we directly observed cyclic transition between the O-configuration and the collapsed B-configuration with a 200 ms temporal resolution. In addition, AFM images show that condensin can bind to the 토토 사이트 using a HEAT repeat domain and a hinge domains (2). Furthermore, using magnetic tweezers, we observed that a condensin uses 40 nm step size to extrude a 토토 사이트 loop, and this length is strikingly similar to the length of the hinge domain and the head domains of the O shape. Our results suggest that condensin extrudes 토토 사이트 by a fast cyclic switching of its conformation between the O and B configurations, consistent with a scrunching model. Secondly, we observed that cohesin complexes phase separate along a 토토 사이트 using a single molecule fluorescence assay (3). AFM images of the clusters showed that the cluster formation is induced by 토토 사이트 bridging by the two distinct 토토 사이트 binding sites in cohesin, supporting polymer-polymer phase separation (PPPS) (4, 5). Strikingly, we observed that the cluster is a liquid droplet by visualizing the merging of two cohesin/토토 사이트 droplets into one spherical droplet. From our observations, we conclude that cohesin induces PPPS, and when many cohesins are collected in a cluster, the cluster stimulates cohesin-cohesin interaction to trigger liquid-liquid phase separation. This is the first direct experimental evidence of PPPS (4, 5) and SMC-mediated phase separation. In conclusion, both 토토 사이트 loop extrusion and phase-separation are fundamental building blocks for organizing chromosome structure. In addition, our results provide a basic principle for genome organization.
Reference
1. Je-Kyung Ryu, et. al., AFM imaging of Condensin architecture for 토토 사이트 loop extrusion, Nature Molecular Structural Biology.
Under review.
2. Mahipal Ganji, et. al., Real-time imaging of 토토 사이트 loop extrusion by condensin. Science. 360, 102–105 2018).
3. Je-Kyung Ryu, et. al., Polymer-polymer phase separation induced by cohesin, Science. In preparation.
4. Fabian Erdel, Karsten Rippe, Formation of Chromatin Subcompartments by Phase Separation. Biophysical Journal. 114, 2262–2270 (2018).
5. Chris A. Brackley, et. al., Nonspecific bridging-induced attraction drives clustering of 토토 사이트-binding proteins and genome organization. Proceedings of the National Academy of Sciences. 110, E3605–E3611 (2013).
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