The structural basis for cohesin-CTCF-anchored loops

被引:259
|
作者
Li, Yan [1 ]
Haarhuis, Judith H. I. [2 ]
Sedeno Cacciatore, Angela [2 ]
Oldenkamp, Roel [2 ]
van Ruiten, Marjon S. [2 ]
Willems, Laureen [2 ]
Teunissen, Hans [3 ]
Muir, Kyle W. [1 ,4 ]
de Wit, Elzo [3 ]
Rowland, Benjamin D. [2 ]
Panne, Daniel [1 ,5 ]
机构
[1] European Mol Biol Lab, Grenoble, France
[2] Netherlands Canc Inst, Div Gene Regulat, Amsterdam, Netherlands
[3] Netherlands Canc Inst, Oncode Inst, Div Gene Regulat, Amsterdam, Netherlands
[4] MRC Lab Mol Biol, Cambridge, England
[5] Univ Leicester, Leicester Inst Struct & Chem Biol, Dept Mol & Cell Biol, Leicester, Leics, England
基金
欧洲研究理事会; 欧盟地平线“2020”;
关键词
FULLY-AUTOMATIC CHARACTERIZATION; HI-C REVEALS; DATA-COLLECTION; 3D GENOME; WAPL; CHROMOSOMES; RESOLUTION; MECHANISM; TOPOLOGY; DOMAINS;
D O I
10.1038/s41586-019-1910-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cohesin catalyses the folding of the genome into loops that are anchored by CTCF1. The molecular mechanism of how cohesin and CTCF structure the 3D genome has remained unclear. Here we show that a segment within the CTCF N terminus interacts with the SA2-SCC1 subunits of human cohesin. We report a crystal structure of SA2-SCC1 in complex with CTCF at a resolution of 2.7 angstrom, which reveals the molecular basis of the interaction. We demonstrate that this interaction is specifically required for CTCF-anchored loops and contributes to the positioning of cohesin at CTCF binding sites. A similar motif is present in a number of established and newly identified cohesin ligands, including the cohesin release factor WAPL(2,3). Our data suggest that CTCF enables the formation of chromatin loops by protecting cohesin against loop release. These results provide fundamental insights into the molecular mechanism that enables the dynamic regulation of chromatin folding by cohesin and CTCF. The crystal structure of the SA2-SCC1 subunits of human cohesin in complex with CTCF reveals the molecular basis of the cohesin-CTCF interaction that enables the dynamic regulation of chromatin folding.
引用
收藏
页码:472 / +
页数:22
相关论文
共 50 条
  • [21] The roles of cohesin and CTCF for shaping the chromatin fiber
    Wendt, K. S.
    Zuin, J.
    Dixon, J. R.
    van der Reijden, M. I. J. A.
    Kolovos, P.
    Ye, Z.
    Brouwer, R. W. W.
    van de Corput, M. P. C.
    van IJcken, W. F. J.
    Grosveld, F. G.
    Ren, B.
    FEBS JOURNAL, 2013, 280 : 4 - 4
  • [22] Cohesin: building loops, but not compartments
    Haarhuis, Judith H. I.
    Rowland, Benjamin D.
    EMBO JOURNAL, 2017, 36 (24): : 3549 - 3551
  • [23] Absolute quantification of cohesin, CTCF and their regulators in human cells
    Holzmann, Johann
    Politi, Antonio Z.
    Nagasaka, Kota
    Hantsche-Grininger, Merle
    Walther, Nike
    Koch, Birgit
    Fuchs, Johannes
    Duernberger, Gerhard
    Tang, Wen
    Ladurner, Rene
    Stocsits, Roman R.
    Busslinger, Georg A.
    Novak, Bela
    Mechtler, Karl
    Davidson, Iain Finley
    Ellenberg, Jan
    Peters, Jan-Michael
    ELIFE, 2019, 8
  • [24] Structural Basis of Eco1-Mediated Cohesin Acetylation
    William C. H. Chao
    Benjamin O. Wade
    Céline Bouchoux
    Andrew W. Jones
    Andrew G. Purkiss
    Stefania Federico
    Nicola O’Reilly
    Ambrosius P. Snijders
    Frank Uhlmann
    Martin R. Singleton
    Scientific Reports, 7
  • [25] Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl
    Georg A. Busslinger
    Roman R. Stocsits
    Petra van der Lelij
    Elin Axelsson
    Antonio Tedeschi
    Niels Galjart
    Jan-Michael Peters
    Nature, 2017, 544 : 503 - 507
  • [26] Cohesin, CTCF and lymphocyte antigen receptor locus rearrangement
    Seitan, Vlad C.
    Krangel, Michael S.
    Merkenschlager, Matthias
    TRENDS IN IMMUNOLOGY, 2012, 33 (04) : 153 - 159
  • [27] How cohesin and CTCF cooperate in regulating gene expression
    Wendt, Kerstin S.
    Peters, Jan-Michael
    CHROMOSOME RESEARCH, 2009, 17 (02) : 201 - 214
  • [28] Structural Basis of Eco1-Mediated Cohesin Acetylation
    Chao, William C. H.
    Wade, Benjamin O.
    Bouchoux, Celine
    Jones, Andrew W.
    Purkiss, Andrew G.
    Federico, Stefania
    O'Reilly, Nicola
    Snijders, Ambrosius P.
    Uhlmann, Frank
    Singleton, Martin R.
    SCIENTIFIC REPORTS, 2017, 7
  • [29] Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl
    Busslinger, Georg A.
    Stocsits, Roman R.
    van der Lelij, Petra
    Axelsson, Elin
    Tedeschi, Antonio
    Galjart, Niels
    Peters, Jan-Michael
    NATURE, 2017, 544 (7651) : 503 - +
  • [30] How cohesin and CTCF cooperate in regulating gene expression
    Kerstin S. Wendt
    Jan-Michael Peters
    Chromosome Research, 2009, 17 : 201 - 214