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dc.contributor.authorEmerson, Daniel J
dc.contributor.authorZhao, Peiyao A
dc.contributor.authorCook, Ashley L
dc.contributor.authorBarnett, R Jordan
dc.contributor.authorKlein, Kyle N
dc.contributor.authorSaulebekova, Dalila
dc.contributor.authorGe, Chunmin
dc.contributor.authorZhou, Linda
dc.contributor.authorSimandi, Zoltan
dc.contributor.authorMinsk, Miriam K
dc.contributor.authorTitus, Katelyn R
dc.contributor.authorWang, Weitao
dc.contributor.authorGong, Wanfeng
dc.contributor.authorZhang, Di
dc.contributor.authorYang, Liyan
dc.contributor.authorVenev, Sergey V
dc.contributor.authorGibcus, Johan H
dc.contributor.authorYang, Hongbo
dc.contributor.authorSasaki, Takayo
dc.contributor.authorKanemaki, Masato T
dc.contributor.authorYue, Feng
dc.contributor.authorDekker, Job
dc.contributor.authorChen, Chun-Long
dc.contributor.authorGilbert, David M
dc.contributor.authorPhillips-Cremins, Jennifer E
dc.date.accessioned2023-11-07T21:06:09Z
dc.date.available2023-11-07T21:06:09Z
dc.date.issued2022-06-08
dc.identifier.citationEmerson DJ, Zhao PA, Cook AL, Barnett RJ, Klein KN, Saulebekova D, Ge C, Zhou L, Simandi Z, Minsk MK, Titus KR, Wang W, Gong W, Zhang D, Yang L, Venev SV, Gibcus JH, Yang H, Sasaki T, Kanemaki MT, Yue F, Dekker J, Chen CL, Gilbert DM, Phillips-Cremins JE. Cohesin-mediated loop anchors confine the locations of human replication origins. Nature. 2022 Jun;606(7915):812-819. doi: 10.1038/s41586-022-04803-0. Epub 2022 Jun 8. PMID: 35676475; PMCID: PMC9217744.en_US
dc.identifier.eissn1476-4687
dc.identifier.doi10.1038/s41586-022-04803-0en_US
dc.identifier.pmid35676475
dc.identifier.urihttp://hdl.handle.net/20.500.14038/52712
dc.description.abstractDNA replication occurs through an intricately regulated series of molecular events and is fundamental for genome stability1,2. At present, it is unknown how the locations of replication origins are determined in the human genome. Here we dissect the role of topologically associating domains (TADs)3-6, subTADs7 and loops8 in the positioning of replication initiation zones (IZs). We stratify TADs and subTADs by the presence of corner-dots indicative of loops and the orientation of CTCF motifs. We find that high-efficiency, early replicating IZs localize to boundaries between adjacent corner-dot TADs anchored by high-density arrays of divergently and convergently oriented CTCF motifs. By contrast, low-efficiency IZs localize to weaker dotless boundaries. Following ablation of cohesin-mediated loop extrusion during G1, high-efficiency IZs become diffuse and delocalized at boundaries with complex CTCF motif orientations. Moreover, G1 knockdown of the cohesin unloading factor WAPL results in gained long-range loops and narrowed localization of IZs at the same boundaries. Finally, targeted deletion or insertion of specific boundaries causes local replication timing shifts consistent with IZ loss or gain, respectively. Our data support a model in which cohesin-mediated loop extrusion and stalling at a subset of genetically encoded TAD and subTAD boundaries is an essential determinant of the locations of replication origins in human S phase.en_US
dc.language.isoenen_US
dc.relation.ispartofNatureen_US
dc.relation.urlhttps://doi.org/10.1038/s41586-022-04803-0en_US
dc.rightsOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2022en_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectChromatin structureen_US
dc.subjectEpigeneticsen_US
dc.subjectEpigenomicsen_US
dc.subjectOrigin selectionen_US
dc.titleCohesin-mediated loop anchors confine the locations of human replication originsen_US
dc.typeJournal Articleen_US
dc.source.journaltitleNature
dc.source.volume606
dc.source.issue7915
dc.source.beginpage812
dc.source.endpage819
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryEngland
dc.identifier.journalNature
refterms.dateFOA2023-11-07T21:06:10Z
dc.contributor.departmentSystems Biologyen_US


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Open Access This article is licensed under a Creative Commons Attribution
4.0 International License, which permits use, sharing, adaptation, distribution
and reproduction in any medium or format, as long as you give appropriate
credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made. The images or other third party material in this article are
included in the article’s Creative Commons license, unless indicated otherwise in a credit line
to the material. If material is not included in the article’s Creative Commons license and your
intended use is not permitted by statutory regulation or exceeds the permitted use, you will
need to obtain permission directly from the copyright holder. To view a copy of this license,
visit http://creativecommons.org/licenses/by/4.0/.
© The Author(s) 2022
Except where otherwise noted, this item's license is described as Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2022