{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T06:53:15Z","timestamp":1782802395777,"version":"3.54.5"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1013843","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000}}],"reference-count":86,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PMRF, MoE, India"},{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board, India","doi-asserted-by":"crossref","award":["CRG\/2022\/008142"],"award-info":[{"award-number":["CRG\/2022\/008142"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Protein molecules must efficiently locate specific DNA sequences within the densely packed chromatin of the cell nucleus. We investigate how the spatial organisation of chromatin, specifically its organisation into Topologically Associating Domains (TADs), fundamentally affects this search process. Using exact analytical theory and simulations of different models of chromatin, we show that target search within compact, highly connected chromatin domains can leverage intersegmental jumps to significantly decrease search times. Further, we establish that there exists an optimal degree of polymer compaction that minimizes the search time for proteins to find their targets. For highly folded domains, our results suggest that rather than bulk diffusion, intersegmental transfers \u2013 jumping between chromatin segments that are close together in space \u2013 drive the optimal search process. Remarkably, when we analyse 8,355 TAD structures across the human genome, we find that their natural connectivity matches with the theoretical optimum predicted by our model. The structural organisation within TADs significantly reduces protein search times far beyond what is achievable through classical facilitated diffusion. In essence, our work suggests that packaging of chromatin inside the nucleus has implications beyond spatial organisation, and is also intricately linked to the dynamics of proteins inside the nuclear environment.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1013843","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T18:53:01Z","timestamp":1768935181000},"page":"e1013843","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Compaction of chromatin domains regulates target search times of proteins"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4373-1589","authenticated-orcid":true,"given":"Shuvadip","family":"Dutta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adarshkrishnan","family":"Rajakumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5485-1474","authenticated-orcid":true,"given":"Ranjith","family":"Padinhateeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1777-7356","authenticated-orcid":true,"given":"Mithun K.","family":"Mitra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"issue":"3","key":"pcbi.1013843.ref001","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/0022-2836(70)90074-4","article-title":"The lac repressor-operator interaction. 3. Kinetic studies","volume":"53","author":"AD Riggs","year":"1970","journal-title":"J Mol Biol."},{"issue":"24","key":"pcbi.1013843.ref002","doi-asserted-by":"crossref","first-page":"6929","DOI":"10.1021\/bi00527a028","article-title":"Diffusion-driven mechanisms of protein translocation on nucleic acids. 1. Models and theory","volume":"20","author":"OG Berg","year":"1981","journal-title":"Biochemistry."},{"issue":"24","key":"pcbi.1013843.ref003","doi-asserted-by":"crossref","first-page":"6961","DOI":"10.1021\/bi00527a030","article-title":"Diffusion-driven mechanisms of protein translocation on nucleic acids. 3. The Escherichia coli lac repressor-operator interaction: kinetic measurements and conclusions","volume":"20","author":"RB Winter","year":"1981","journal-title":"Biochemistry."},{"issue":"2","key":"pcbi.1013843.ref004","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/S0021-9258(19)84994-3","article-title":"Facilitated target location in biological systems","volume":"264","author":"PH von Hippel","year":"1989","journal-title":"J Biol Chem."},{"key":"pcbi.1013843.ref005","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1042\/bst0290363","article-title":"Hopping, jumping and looping by restriction enzymes","volume":"29","author":"SE Halford","year":"2001","journal-title":"Biochem Soc Trans."},{"issue":"10","key":"pcbi.1013843.ref006","doi-asserted-by":"crossref","first-page":"3040","DOI":"10.1093\/nar\/gkh624","article-title":"How do site-specific DNA-binding proteins find their targets?","volume":"32","author":"SE Halford","year":"2004","journal-title":"Nucleic Acids Res."},{"issue":"47","key":"pcbi.1013843.ref007","doi-asserted-by":"crossref","first-page":"16909","DOI":"10.1073\/pnas.0508686102","article-title":"Target site localization by site-specific, DNA-binding proteins","volume":"102","author":"J Widom","year":"2005","journal-title":"Proc Natl Acad Sci U S A."},{"key":"pcbi.1013843.ref008","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1146\/annurev.bb.14.060185.001023","article-title":"Diffusion-controlled macromolecular interactions","volume":"14","author":"OG Berg","year":"1985","journal-title":"Annu Rev Biophys Biophys Chem."},{"issue":"2","key":"pcbi.1013843.ref009","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/S0021-9258(19)84994-3","article-title":"Facilitated target location in biological systems","volume":"264","author":"PH von Hippel","year":"1989","journal-title":"J Biol Chem."},{"issue":"12","key":"pcbi.1013843.ref010","doi-asserted-by":"crossref","first-page":"4118","DOI":"10.1093\/nar\/gkn376","article-title":"Sliding and jumping of single EcoRV restriction enzymes on non-cognate DNA","volume":"36","author":"I Bonnet","year":"2008","journal-title":"Nucleic Acids Res."},{"issue":"5828","key":"pcbi.1013843.ref011","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1126\/science.1141967","article-title":"Probing transcription factor dynamics at the single-molecule level in a living cell","volume":"316","author":"J Elf","year":"2007","journal-title":"Science."},{"issue":"1","key":"pcbi.1013843.ref012","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/s41467-019-14217-8","article-title":"Eukaryotic transcription factors can track and control their target genes using DNA antennas","volume":"11","author":"M Castellanos","year":"2020","journal-title":"Nat Commun."},{"issue":"8","key":"pcbi.1013843.ref013","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/nsmb.1441","article-title":"Visualizing one-dimensional diffusion of proteins along DNA","volume":"15","author":"J Gorman","year":"2008","journal-title":"Nat Struct Mol Biol."},{"issue":"11","key":"pcbi.1013843.ref014","doi-asserted-by":"crossref","first-page":"3848","DOI":"10.1093\/nar\/gkm332","article-title":"Single-molecule analysis of 1D diffusion and transcription elongation of T7 RNA polymerase along individual stretched DNA molecules","volume":"35","author":"JH Kim","year":"2007","journal-title":"Nucleic Acids Res."},{"issue":"15","key":"pcbi.1013843.ref015","doi-asserted-by":"crossref","first-page":"5752","DOI":"10.1073\/pnas.0509723103","article-title":"A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA","volume":"103","author":"PC Blainey","year":"2006","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"5","key":"pcbi.1013843.ref016","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1073\/pnas.0508366103","article-title":"Long-distance lateral diffusion of human Rad51 on double-stranded DNA","volume":"103","author":"A Gran\u00e9li","year":"2006","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"4","key":"pcbi.1013843.ref017","doi-asserted-by":"crossref","first-page":"048302","DOI":"10.1103\/PhysRevLett.97.048302","article-title":"Single molecule measurements of repressor protein 1D diffusion on DNA","volume":"97","author":"YM Wang","year":"2006","journal-title":"Phys Rev Lett."},{"issue":"19","key":"pcbi.1013843.ref018","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1016\/j.jmb.2015.07.015","article-title":"DNA-segment-facilitated dissociation of Fis and NHP6A from DNA detected via single-molecule mechanical response","volume":"427","author":"RD Giuntoli","year":"2015","journal-title":"J Mol Biol."},{"issue":"14","key":"pcbi.1013843.ref019","doi-asserted-by":"crossref","first-page":"148101","DOI":"10.1103\/PhysRevLett.121.148101","article-title":"Surface fluctuations and coalescence of nucleolar droplets in the human cell nucleus","volume":"121","author":"CM Caragine","year":"2018","journal-title":"Phys Rev Lett."},{"issue":"15","key":"pcbi.1013843.ref020","doi-asserted-by":"crossref","first-page":"8642","DOI":"10.1093\/nar\/gkab658","article-title":"Testing mechanisms of DNA sliding by architectural DNA-binding proteins: dynamics of single wild-type and mutant protein molecules in vitro and in vivo","volume":"49","author":"K Kamagata","year":"2021","journal-title":"Nucleic Acids Res."},{"issue":"13","key":"pcbi.1013843.ref021","doi-asserted-by":"crossref","first-page":"6654","DOI":"10.1093\/nar\/gkad471","article-title":"Single-molecule characterization of target search dynamics of DNA-binding proteins in DNA-condensed droplets","volume":"51","author":"K Kamagata","year":"2023","journal-title":"Nucleic Acids Res."},{"issue":"4","key":"pcbi.1013843.ref022","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.cell.2007.01.028","article-title":"Beyond the sequence: cellular organization of genome function","volume":"128","author":"T Misteli","year":"2007","journal-title":"Cell."},{"issue":"6","key":"pcbi.1013843.ref023","article-title":"Predicting three-dimensional genome organization with chromatin states","volume":"15","author":"Y Qi","year":"2019","journal-title":"PLoS Comput Biol."},{"issue":"1","key":"pcbi.1013843.ref024","first-page":"011051","article-title":"From Hi-C contact map to three-dimensional organization of interphase human chromosomes","volume":"11","author":"G Shi","year":"2021","journal-title":"Phys Rev X."},{"issue":"43","key":"pcbi.1013843.ref025","doi-asserted-by":"crossref","first-page":"12168","DOI":"10.1073\/pnas.1613607113","article-title":"Transferable model for chromosome architecture","volume":"113","author":"M Di Pierro","year":"2016","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"3","key":"pcbi.1013843.ref026","article-title":"Resolving the 3D landscape of transcription-linked mammalian chromatin folding","volume":"78","author":"T-HS Hsieh","year":"2020","journal-title":"Mol Cell."},{"issue":"1","key":"pcbi.1013843.ref027","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.cell.2020.09.014","article-title":"The self-organizing genome: principles of genome architecture and function","volume":"183","author":"T Misteli","year":"2020","journal-title":"Cell."},{"issue":"1","key":"pcbi.1013843.ref028","doi-asserted-by":"crossref","first-page":"4108","DOI":"10.1038\/s41467-023-39907-2","article-title":"Predicting scale-dependent chromatin polymer properties from systematic coarse-graining","volume":"14","author":"S Kadam","year":"2023","journal-title":"Nat Commun."},{"issue":"1","key":"pcbi.1013843.ref029","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1039\/D2SM00612J","article-title":"Multivalent binding proteins can drive collapse and reswelling of chromatin in confinement","volume":"19","author":"S Guha","year":"2022","journal-title":"Soft Matter."},{"issue":"7398","key":"pcbi.1013843.ref030","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nature11049","article-title":"Spatial partitioning of the regulatory landscape of the X-inactivation centre","volume":"485","author":"EP Nora","year":"2012","journal-title":"Nature."},{"issue":"7398","key":"pcbi.1013843.ref031","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature11082","article-title":"Topological domains in mammalian genomes identified by analysis of chromatin interactions","volume":"485","author":"JR Dixon","year":"2012","journal-title":"Nature."},{"issue":"4","key":"pcbi.1013843.ref032","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aaw1668","article-title":"Principles of genome folding into topologically associating domains","volume":"5","author":"Q Szabo","year":"2019","journal-title":"Sci Adv."},{"issue":"3","key":"pcbi.1013843.ref033","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.jmb.2019.09.026","article-title":"TADs as the caller calls them","volume":"432","author":"E de Wit","year":"2020","journal-title":"J Mol Biol."},{"issue":"47","key":"pcbi.1013843.ref034","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1518552112","article-title":"Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes","volume":"112","author":"AL Sanborn","year":"2015","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"15","key":"pcbi.1013843.ref035","doi-asserted-by":"crossref","first-page":"9553","DOI":"10.1093\/nar\/gku698","article-title":"Modeling epigenome folding: formation and dynamics of topologically associated chromatin domains","volume":"42","author":"D Jost","year":"2014","journal-title":"Nucleic Acids Res."},{"issue":"1","key":"pcbi.1013843.ref036","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.cell.2015.05.048","article-title":"Mapping nucleosome resolution chromosome folding in yeast by micro-C","volume":"162","author":"T-HS Hsieh","year":"2015","journal-title":"Cell."},{"key":"pcbi.1013843.ref037","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1146\/annurev-genom-091212-153515","article-title":"The spatial organization of the human genome","volume":"14","author":"WA Bickmore","year":"2013","journal-title":"Annu Rev Genomics Hum Genet."},{"key":"pcbi.1013843.ref038","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.gde.2020.12.015","article-title":"To loop or not to loop: what is the role of TADs in enhancer function and gene regulation?","volume":"67","author":"GR Cavalheiro","year":"2021","journal-title":"Curr Opin Genet Dev."},{"issue":"5950","key":"pcbi.1013843.ref039","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1126\/science.1181369","article-title":"Comprehensive mapping of long-range interactions reveals folding principles of the human genome","volume":"326","author":"E Lieberman-Aiden","year":"2009","journal-title":"Science."},{"issue":"23","key":"pcbi.1013843.ref040","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2222078120","article-title":"Theory of chromatin organization maintained by active loop extrusion","volume":"120","author":"B Chan","year":"2023","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"1","key":"pcbi.1013843.ref041","doi-asserted-by":"crossref","first-page":"6433","DOI":"10.1038\/s41467-023-42133-5","article-title":"Chromatin organization drives the search mechanism of nuclear factors","volume":"14","author":"M Mazzocca","year":"2023","journal-title":"Nat Commun."},{"issue":"7","key":"pcbi.1013843.ref042","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1016\/j.cell.2014.11.021","article-title":"A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping","volume":"159","author":"SSP Rao","year":"2014","journal-title":"Cell."},{"issue":"5","key":"pcbi.1013843.ref043","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1103\/PhysRevLett.79.857","article-title":"Paradoxal diffusion in chemical space for nearest-neighbor walks over polymer chains","volume":"79","author":"IM Sokolov","year":"1997","journal-title":"Phys Rev Lett."},{"key":"pcbi.1013843.ref044","doi-asserted-by":"crossref","first-page":"051911","DOI":"10.1103\/PhysRevE.84.051911","article-title":"Target search on a dynamic DNA molecule","volume":"84","author":"T Sch\u00f6tz","year":"2011","journal-title":"Phys Rev E Stat Nonlin Soft Matter Phys."},{"issue":"3","key":"pcbi.1013843.ref045","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.cell.2012.01.010","article-title":"Three-dimensional folding and functional organization principles of the Drosophila genome","volume":"148","author":"T Sexton","year":"2012","journal-title":"Cell."},{"issue":"16","key":"pcbi.1013843.ref046","doi-asserted-by":"crossref","first-page":"168103","DOI":"10.1103\/PhysRevLett.109.168103","article-title":"Facilitated diffusion on mobile DNA: configurational traps and sequence heterogeneity","volume":"109","author":"CA Brackley","year":"2012","journal-title":"Phys Rev Lett."},{"issue":"40","key":"pcbi.1013843.ref047","doi-asserted-by":"crossref","first-page":"9372","DOI":"10.1021\/acs.jpcb.7b08199","article-title":"Understanding the role of DNA topology in target search dynamics of proteins","volume":"121","author":"A Mondal","year":"2017","journal-title":"J Phys Chem B."},{"issue":"17","key":"pcbi.1013843.ref048","doi-asserted-by":"crossref","first-page":"3518","DOI":"10.1021\/acs.jpcb.0c01996","article-title":"Effect of DNA conformation on the protein search for targets on DNA: a theoretical perspective","volume":"124","author":"K Mondal","year":"2020","journal-title":"J Phys Chem B."},{"issue":"42","key":"pcbi.1013843.ref049","doi-asserted-by":"crossref","first-page":"12695","DOI":"10.1021\/jp311466f","article-title":"Speed-selectivity paradox in the protein search for targets on DNA: is it real or not?","volume":"117","author":"A Veksler","year":"2013","journal-title":"J Phys Chem B."},{"issue":"43","key":"pcbi.1013843.ref050","doi-asserted-by":"crossref","first-page":"434013","DOI":"10.1088\/1751-8113\/42\/43\/434013","article-title":"How a protein searches for its site on DNA: the mechanism of facilitated diffusion","volume":"42","author":"L Mirny","year":"2009","journal-title":"J Phys A: Math Theor."},{"issue":"1","key":"pcbi.1013843.ref051","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1080\/19491034.2017.1389365","article-title":"Recent evidence that TADs and chromatin loops are dynamic structures","volume":"9","author":"AS Hansen","year":"2018","journal-title":"Nucleus."},{"issue":"3","key":"pcbi.1013843.ref052","doi-asserted-by":"crossref","DOI":"10.1016\/j.bpj.2017.11.211","article-title":"Chromatin organization by an interplay of loop extrusion and compartmental segregation","volume":"114","author":"J Nuebler","year":"2018","journal-title":"Biophysical Journal."},{"issue":"4","key":"pcbi.1013843.ref053","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1016\/S0006-3495(01)76164-4","article-title":"DNA folding: structural and mechanical properties of the two-angle model for chromatin","volume":"80","author":"H Schiessel","year":"2001","journal-title":"Biophys J."},{"issue":"1","key":"pcbi.1013843.ref054","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1005365","article-title":"Binding of DNA-bending non-histone proteins destabilizes regular 30-nm chromatin structure","volume":"13","author":"G Bajpai","year":"2017","journal-title":"PLoS Comput Biol."},{"key":"pcbi.1013843.ref055","unstructured":"Rubinsten M. Polymer physics. United States of America; 2003."},{"key":"pcbi.1013843.ref056","doi-asserted-by":"crossref","first-page":"108171","DOI":"10.1016\/j.cpc.2021.108171","article-title":"LAMMPS - a flexible simulation tool for particle-based materials modeling at the atomic, meso, and continuum scales","volume":"271","author":"AP Thompson","year":"2022","journal-title":"Computer Physics Communications."},{"issue":"3","key":"pcbi.1013843.ref057","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1093\/imanum\/drs019","article-title":"A fast algorithm for matrix balancing","volume":"33","author":"PA Knight","year":"2012","journal-title":"IMA Journal of Numerical Analysis."},{"issue":"9","key":"pcbi.1013843.ref058","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1016\/j.bpj.2020.02.017","article-title":"Computing 3D chromatin configurations from contact probability maps by inverse Brownian dynamics","volume":"118","author":"K Kumari","year":"2020","journal-title":"Biophys J."},{"issue":"7","key":"pcbi.1013843.ref059","doi-asserted-by":"crossref","DOI":"10.1016\/j.molcel.2021.01.039","article-title":"Transient non-specific DNA binding dominates the target search of bacterial DNA-binding proteins","volume":"81","author":"M Stracy","year":"2021","journal-title":"Mol Cell."},{"issue":"17","key":"pcbi.1013843.ref060","doi-asserted-by":"crossref","first-page":"3816","DOI":"10.1021\/acs.jpcb.2c09142","article-title":"RNAP promoter search and transcription kinetics in live E. coli cells","volume":"127","author":"K Bettridge","year":"2023","journal-title":"J Phys Chem B."},{"issue":"13","key":"pcbi.1013843.ref061","doi-asserted-by":"crossref","first-page":"6654","DOI":"10.1093\/nar\/gkad471","article-title":"Single-molecule characterization of target search dynamics of DNA-binding proteins in DNA-condensed droplets","volume":"51","author":"K Kamagata","year":"2023","journal-title":"Nucleic Acids Res."},{"issue":"2","key":"pcbi.1013843.ref062","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1073\/pnas.1016020107","article-title":"A single-molecule characterization of p53 search on DNA","volume":"108","author":"A Tafvizi","year":"2011","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"6349","key":"pcbi.1013843.ref063","article-title":"ChromEMT: visualizing 3D chromatin structure and compaction in interphase and mitotic cells","volume":"357","author":"HD Ou","year":"2017","journal-title":"Science."},{"key":"pcbi.1013843.ref064","doi-asserted-by":"crossref","unstructured":"Redner S. A guide to first-passage processes. a guide to first-passage processes. Cambridge University Press; 2001. https:\/\/books.google.co.in\/books?id=xtsqMh3VC98C.","DOI":"10.1017\/CBO9780511606014"},{"issue":"1","key":"pcbi.1013843.ref065","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1088\/0305-4470\/38\/1\/007","article-title":"First-passage properties of the Erdos\u2013Renyi random graph","volume":"38","author":"V Sood","year":"2004","journal-title":"J Phys A: Math Gen."},{"issue":"11","key":"pcbi.1013843.ref066","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2413112122","article-title":"Insulation between adjacent TADs is controlled by the width of their boundaries through distinct mechanisms","volume":"122","author":"A Papale","year":"2025","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"2","key":"pcbi.1013843.ref067","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aar8082","article-title":"TADs are 3D structural units of higher-order chromosome organization in Drosophila","volume":"4","author":"Q Szabo","year":"2018","journal-title":"Sci Adv."},{"issue":"16","key":"pcbi.1013843.ref068","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1016\/j.jmb.2015.06.016","article-title":"One-dimensional sliding of p53 along DNA is accelerated in the presence of Ca(2+) or Mg(2+) at millimolar concentrations","volume":"427","author":"A Murata","year":"2015","journal-title":"J Mol Biol."},{"issue":"4","key":"pcbi.1013843.ref069","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1005469","article-title":"Transient chromatin properties revealed by polymer models and stochastic simulations constructed from chromosomal capture data","volume":"13","author":"O Shukron","year":"2017","journal-title":"PLoS Comput Biol."},{"issue":"8","key":"pcbi.1013843.ref070","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.1093\/nar\/gkw135","article-title":"Simulated binding of transcription factors to active and inactive regions folds human chromosomes into loops, rosettes and topological domains","volume":"44","author":"CA Brackley","year":"2016","journal-title":"Nucleic Acids Res."},{"issue":"4","key":"pcbi.1013843.ref071","doi-asserted-by":"crossref","DOI":"10.1016\/j.molcel.2018.09.016","article-title":"Polymer simulations of heteromorphic chromatin predict the 3D folding of complex genomic loci","volume":"72","author":"A Buckle","year":"2018","journal-title":"Mol Cell."},{"issue":"1","key":"pcbi.1013843.ref072","doi-asserted-by":"crossref","first-page":"013010","DOI":"10.1103\/PRXLife.1.013010","article-title":"From effective interactions extracted using Hi-C data to chromosome structures in conventional and inverted nuclei","volume":"1","author":"S Shin","year":"2023","journal-title":"PRX Life."},{"issue":"6161","key":"pcbi.1013843.ref073","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1126\/science.1236083","article-title":"Organization of the mitotic chromosome","volume":"342","author":"N Naumova","year":"2013","journal-title":"Science."},{"issue":"1","key":"pcbi.1013843.ref074","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s10577-010-9177-0","article-title":"The fractal globule as a model of chromatin architecture in the cell","volume":"19","author":"LA Mirny","year":"2011","journal-title":"Chromosome Res."},{"issue":"22","key":"pcbi.1013843.ref075","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2109838119","article-title":"Generation of dynamic three-dimensional genome structure through phase separation of chromatin","volume":"119","author":"S Fujishiro","year":"2022","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"41","key":"pcbi.1013843.ref076","doi-asserted-by":"crossref","first-page":"15738","DOI":"10.1073\/pnas.0804248105","article-title":"How DNA coiling enhances target localization by proteins","volume":"105","author":"B van den Broek","year":"2008","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"5","key":"pcbi.1013843.ref077","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.1063\/1.458605","article-title":"The effects of internal constraints on the configurations of chain molecules","volume":"92","author":"HS Chan","year":"1990","journal-title":"The Journal of Chemical Physics."},{"issue":"26","key":"pcbi.1013843.ref078","doi-asserted-by":"crossref","first-page":"260603","DOI":"10.1103\/PhysRevLett.95.260603","article-title":"Optimal target search on a fast-folding polymer chain with volume exchange","volume":"95","author":"MA Lomholt","year":"2005","journal-title":"Phys Rev Lett."},{"key":"pcbi.1013843.ref079","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1146\/annurev-biophys-052118-115638","article-title":"How the genome folds: the biophysics of four-dimensional chromatin organization","volume":"48","author":"JJ Parmar","year":"2019","journal-title":"Annu Rev Biophys."},{"issue":"10","key":"pcbi.1013843.ref080","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1016\/j.bpj.2016.02.041","article-title":"Chromosome compaction by active loop extrusion","volume":"110","author":"A Goloborodko","year":"2016","journal-title":"Biophys J."},{"issue":"7662","key":"pcbi.1013843.ref081","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/nature22822","article-title":"Liquid droplet formation by HP1\u03b1 suggests a role for phase separation in heterochromatin","volume":"547","author":"AG Larson","year":"2017","journal-title":"Nature."},{"issue":"3","key":"pcbi.1013843.ref082","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/ncb1845","article-title":"The heterochromatin protein Swi6\/HP1 activates replication origins at the pericentromeric region and silent mating-type locus","volume":"11","author":"MT Hayashi","year":"2009","journal-title":"Nat Cell Biol."},{"issue":"22","key":"pcbi.1013843.ref083","doi-asserted-by":"crossref","first-page":"8303","DOI":"10.1128\/MCB.00887-06","article-title":"Transcriptional coactivator PC4, a chromatin-associated protein, induces chromatin condensation","volume":"26","author":"C Das","year":"2006","journal-title":"Mol Cell Biol."},{"issue":"2","key":"pcbi.1013843.ref084","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1073\/pnas.1713895115","article-title":"Visualizing long-term single-molecule dynamics in vivo by stochastic protein labeling","volume":"115","author":"H Liu","year":"2018","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"6","key":"pcbi.1013843.ref085","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1016\/j.cell.2013.02.011","article-title":"Chromatin remodeling at DNA double-strand breaks","volume":"152","author":"BD Price","year":"2013","journal-title":"Cell."},{"issue":"24","key":"pcbi.1013843.ref086","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.ade1122","article-title":"Dynamic switching of transcriptional regulators between two distinct low-mobility chromatin states","volume":"9","author":"K Wagh","year":"2023","journal-title":"Sci Adv."}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1013843","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000}}],"container-title":["PLOS Computational 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