@article{f4719c85a4de4fcf907b9aba947be62e,
title = "The Cohesin Release Factor WAPL Restricts Chromatin Loop Extension",
abstract = "The spatial organization of chromosomes influences many nuclear processes including gene expression. The cohesin complex shapes the 3D genome by looping together CTCF sites along chromosomes. We show here that chromatin loop size can be increased and that the duration with which cohesin embraces DNA determines the degree to which loops are enlarged. Cohesin's DNA release factor WAPL restricts this loop extension and also prevents looping between incorrectly oriented CTCF sites. We reveal that the SCC2/SCC4 complex promotes the extension of chromatin loops and the formation of topologically associated domains (TADs). Our data support the model that cohesin structures chromosomes through the processive enlargement of loops and that TADs reflect polyclonal collections of loops in the making. Finally, we find that whereas cohesin promotes chromosomal looping, it rather limits nuclear compartmentalization. We conclude that the balanced activity of SCC2/SCC4 and WAPL enables cohesin to correctly structure chromosomes.",
keywords = "chromatin looping, cohesin, CTCF, loop extrusion, MAU2, NIPBL, SCC2, SCC4, TADs, WAPL",
author = "Haarhuis, {Judith H.I.} and {van der Weide}, {Robin H.} and Blomen, {Vincent A.} and Y{\'a}{\~n}ez-Cuna, {J. Omar} and Mario Amendola and {van Ruiten}, {Marjon S.} and Krijger, {Peter H. L.} and Hans Teunissen and Medema, {Ren{\'e} H.} and {van Steensel}, Bas and Brummelkamp, {Thijn R.} and {de Wit}, Elzo and Rowland, {Benjamin D.}",
note = "Funding Information: We are grateful to the Medema laboratory and Ahmed Elbatsh for helpful discussions, Kim Nasmyth for encouragement, Wouter de Laat for support, Max van Osch for technical assistance, Bram van den Broek, Suzan Stelloo, and Sandra de Vries for technical advice, Tao Chen for antibodies, and the NKI Genomics Core and Digital Microscopy facilities for assistance. This work was funded by grants from the Dutch Cancer Society (KWF) (NKI 2010-4706, NKI 2011-5103, and NKI 2015-7657 to B.D.R.), the European Research Council (ERC Starting Grant 637587 HAP-PHEN to E.d.W. and ERC Advanced Grant 293662 to B.v.S.), the Cancer Genomics Center (CGC.nl to T.R.B.), and an EMBO Long Term Fellowship (to J.O.Y.-C.). T.R.B. is a co-founder of Haplogen and Scenic Biotech. Publisher Copyright: {\textcopyright} 2017 The Authors",
year = "2017",
month = may,
day = "4",
doi = "10.1016/j.cell.2017.04.013",
language = "English",
volume = "169",
pages = "693--707.e14",
number = "4",
}