CTCF organizes inter-A compartment interactions through RYBP-dependent phase separation  

作　　者：Chao Wei Lumeng Jia Xiaona Huang Jin Tan Mulan Wang Jing Niu Yingping Hou Jun Sun Pengguihang Zeng Jia Wang Li Qing Lin Ma Xinyi Liu Xiuxiao Tang Fenjie Li Shaoshuai Jiang Jingxin Liu Tingting Li Lili Fan Yujie Sun Juntao Gao Cheng Li Junjun Ding 

机构地区：[1]RNA Biomedical Institute,Sun Yat-Sen Memorial Hospital,Zhongshan School of Medicine,Sun Yat-Sen University,Guangzhou,Guangdong,China [2]Advanced Medical Technology Center,The First Affiliated Hospital,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou,Guangdong,China [3]Center for Stem Cell Biology and Tissue Engineering,Key Laboratory for Stem Cells and Tissue Engineering,Ministry of Education,Zhongshan School of Medicine,Sun Yat-Sen University,Guangzhou,Guangdong,China [4]School of Life Sciences,Peking University,Beijing,China [5]School of Medicine,Tsinghua University,Beijing,China [6]Peking-Tsinghua Center for Life Sciences,Academy for Advanced Interdisciplinary Studies,Peking University,Beijing,China [7]Department of Cell Biology,School of Basic Medical Sciences,Southern Medical University,Guangzhou,Guangdong,China [8]Department of Pediatric Surgery,Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease,Guangzhou Women and Children’s Medical Center,Guangzhou Medical University,Guangzhou,Guangdong,China [9]State Key Laboratory of Proteomics,National Center of Biomedical Analysis,Institute of Basic Medical Sciences,Beijing,China [10]Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine,School of Traditional Chinese Medicine,Jinan University,Guangzhou,Guangdong,China [11]State Key Laboratory of Membrane Biology,Biomedical pioneering innovation center(BIOPIC),Peking University,Beijing,China [12]MOE Key Laboratory of Bioinformatics,Bioinformatics Division,BNRist,Department of Automation,Center for Synthetic&Systems Biology,Tsinghua University,Beijing,China [13]Center for Bioinformatics,Center for Statistical Science,Peking University,Beijing,China

出　　处：《Cell Research》2022年第8期744-760,共17页细胞研究（英文版）

基　　金：funded by grants from the National Key R&D Program(2017YFA0102800);the National Natural Science Foundation of China(31970811,31771639 and 32170798);the Guangdong Regenerative Medicine and Health of Guangdong Laboratory Frontier Exploration Project(2018GZR110105007);the Guangdong Innovative and Entrepreneurial Research Team Program(2016ZT06S029);Guangdong Basic and Applied Basic Research Foundation(2021B1515120063)to J.D.;the National Natural Science Foundation of China(32100497);Post-doctoral Program(2021M703760)to C.W.;the Fundamental Research Funds for the Central Universities of Jinan University(Natural Science)(116210004);China Postdoctoral Science Foundation(55350600);the Natural Science Foundation of Guangdong Province,China(2021A1515010938)to J.S.;the National Natural Science Foundation of China(31900519)to F.L.;the Natural Science Foundation of China(32025006,31871266);National Key R&D Program of China(2021YFA1100300,2016YFA0100103)to L.J.and C.L.;Part of the data analysis was performed on the High Performance Computing Platform of the Center for Life Sciences,Peking University.This work was also supported in part by the State Key R&D Program of China(2017YFA0505503);the National Natural Science Foundation of China(81890991);CAS Interdisciplinary Innovation Team(JCTD-2020-04);Beijing Municipal Natural Science Foundation(Z200021)to J.G.For FISH experiment。

摘　　要：Chromatin is spatially organized into three-dimensional structures at different levels including A/B compartments, topologically associating domains and loops. The canonical CTCF-mediated loop extrusion model can explain the formation of loops. However, the organization mechanisms underlying long-range chromatin interactions such as interactions between A–A compartments are still poorly understood. Here we show that different from the canonical loop extrusion model, RYBP-mediated phase separation of CTCF organizes inter-A compartment interactions. Based on this model, we designed and verified an induced CTCF phase separation system in embryonic stem cells (ESCs), which facilitated inter-A compartment interactions, improved self-renewal of ESCs and inhibited their differentiation toward neural progenitor cells. These findings support a novel and non-canonical role of CTCF in organizing long-range chromatin interactions via phase separation.

关 键 词：CTCF RYBP SEPARATION 

分 类 号：Q2[生物学—细胞生物学]