{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:20:50Z","timestamp":1791490850973,"version":"4.3.4"},"reference-count":61,"publisher":"Life Science Alliance, LLC","issue":"2","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"HFSPO","award":["RGP0044"],"award-info":[{"award-number":["RGP0044"]}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["AAPG-18-CE12-006"],"award-info":[{"award-number":["AAPG-18-CE12-006"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2020-115696RB-I00"],"award-info":[{"award-number":["PID2020-115696RB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"HHS | NIH | National Human Genome Research Institute","doi-asserted-by":"publisher","award":["HG003143"],"award-info":[{"award-number":["HG003143"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["life-science-alliance.org"],"crossmark-restriction":true},"short-container-title":["Life Sci. Alliance"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:p>The genome is organized in functional compartments and structural domains at the sub-megabase scale. How within these domains interactions between numerous cis-acting enhancers and promoters regulate transcription remains an open question. Here, we determined chromatin folding and composition over several hundred kb around estrogen-responsive genes in human breast cancer cell lines after hormone stimulation. Modeling of 5C data at 1.8 kb resolution was combined with quantitative 3D analysis of multicolor FISH measurements at 100 nm resolution and integrated with ChIP-seq data on transcription factor binding and histone modifications. We found that rapid estradiol induction of the progesterone gene expression occurs in the context of preexisting, cell type-specific chromosomal architectures encompassing the 90 kb progesterone gene coding region and an enhancer-spiked 5\u2032 300 kb upstream genomic region. In response to estradiol, interactions between estrogen receptor \u03b1 (ER\u03b1) bound regulatory elements are reinforced. Whereas initial enhancer\u2013gene contacts coincide with RNA Pol 2 binding and transcription initiation, sustained hormone stimulation promotes ER\u03b1 accumulation creating a regulatory hub stimulating transcript synthesis. In addition to implications for estrogen receptor signaling, we uncover that preestablished chromatin architectures efficiently regulate gene expression upon stimulation without the need for de novo extensive rewiring of long-range chromatin interactions.<\/jats:p>","DOI":"10.26508\/lsa.202302154","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T13:00:14Z","timestamp":1700571614000},"page":"e202302154","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Enhancer-driven 3D chromatin domain folding modulates transcription in human mammary tumor cells"],"prefix":"10.26508","volume":"7","author":[{"given":"Silvia","family":"Kocanova","sequence":"first","affiliation":[{"name":"Molecular, Cellular and Developmental Biology Unit (MCD), Centre de Biologie Integrative (CBI), University of Toulouse, UPS, CNRS, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2381-0060","authenticated-orcid":true,"given":"Flavien","family":"Raynal","sequence":"additional","affiliation":[{"name":"Molecular, Cellular and Developmental Biology Unit (MCD), Centre de Biologie Integrative (CBI), University of Toulouse, UPS, CNRS, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8681-7916","authenticated-orcid":true,"given":"Isabelle","family":"Goiffon","sequence":"additional","affiliation":[{"name":"Molecular, Cellular and Developmental Biology Unit (MCD), Centre de Biologie Integrative (CBI), University of Toulouse, UPS, CNRS, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0177-4193","authenticated-orcid":true,"given":"Betul Akgol","family":"Oksuz","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0464eyp60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Systems Biology, University of Massachusetts Chan Medical School","place":[", Worcester, MA, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Ba\u00fa","sequence":"additional","affiliation":[{"name":"Centre Nacional d\u2019An\u00e0lisi Gen\u00f2mica (CNAG), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0866-4154","authenticated-orcid":true,"given":"Alain","family":"Kamgou\u00e9","sequence":"additional","affiliation":[{"name":"Molecular, Cellular and Developmental Biology Unit (MCD), Centre de Biologie Integrative (CBI), University of Toulouse, UPS, CNRS, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Cantaloube","sequence":"additional","affiliation":[{"name":"Molecular, Cellular and Developmental Biology Unit (MCD), Centre de Biologie Integrative (CBI), University of Toulouse, UPS, CNRS, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9280-1718","authenticated-orcid":true,"given":"Ye","family":"Zhan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0464eyp60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Systems Biology, University of Massachusetts Chan Medical School","place":[", Worcester, MA, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Lajoie","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0464eyp60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Systems Biology, University of Massachusetts Chan Medical School","place":[", Worcester, MA, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0151-4279","authenticated-orcid":true,"given":"Marc A","family":"Marti-Renom","sequence":"additional","affiliation":[{"name":"Centre Nacional d\u2019An\u00e0lisi Gen\u00f2mica (CNAG), Barcelona, Spain"},{"name":"Genome Biology Program, Centre de Regulaci\u00f3 Gen\u00f2mica (CRG), Barcelona, Spain"},{"name":"Universitat Pompeu Fabra (UPF), Barcelona, Spain"},{"name":"Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5631-0698","authenticated-orcid":true,"given":"Job","family":"Dekker","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0464eyp60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Systems Biology, University of Massachusetts Chan Medical School","place":[", Worcester, MA, USA"]},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6717-3721","authenticated-orcid":true,"given":"Kerstin","family":"Bystricky","sequence":"additional","affiliation":[{"name":"Molecular, Cellular and Developmental Biology Unit (MCD), Centre de Biologie Integrative (CBI), University of Toulouse, UPS, CNRS, Toulouse, France"},{"name":"Institut Universitaire de France (IUF), Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"12380","published-online":{"date-parts":[[2023,11,21]]},"reference":[{"key":"2024010809170382000_7.2.e202302154.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10005-6"},{"key":"2024010809170382000_7.2.e202302154.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01527-x"},{"key":"2024010809170382000_7.2.e202302154.3","doi-asserted-by":"publisher","DOI":"10.1038\/ng1901"},{"key":"2024010809170382000_7.2.e202302154.4","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60312"},{"key":"2024010809170382000_7.2.e202302154.5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011011"},{"key":"2024010809170382000_7.2.e202302154.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16396-1"},{"key":"2024010809170382000_7.2.e202302154.7","doi-asserted-by":"publisher","DOI":"10.1101\/gr.5571506"},{"key":"2024010809170382000_7.2.e202302154.8","doi-asserted-by":"publisher","DOI":"10.1038\/nature11247"},{"key":"2024010809170382000_7.2.e202302154.9","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15373"},{"key":"2024010809170382000_7.2.e202302154.10","doi-asserted-by":"publisher","DOI":"10.1038\/nature08497"},{"key":"2024010809170382000_7.2.e202302154.11","doi-asserted-by":"publisher","DOI":"10.1101\/111179"},{"key":"2024010809170382000_7.2.e202302154.12","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq175"},{"key":"2024010809170382000_7.2.e202302154.13","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202317"},{"key":"2024010809170382000_7.2.e202302154.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.02.011"},{"key":"2024010809170382000_7.2.e202302154.15","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-1081-2"},{"key":"2024010809170382000_7.2.e202302154.16","doi-asserted-by":"publisher","DOI":"10.1210\/me.2014-1130"},{"key":"2024010809170382000_7.2.e202302154.17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1420404112"},{"key":"2024010809170382000_7.2.e202302154.18","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2148"},{"key":"2024010809170382000_7.2.e202302154.19","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10090331"},{"key":"2024010809170382000_7.2.e202302154.20","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2010.109"},{"key":"2024010809170382000_7.2.e202302154.21","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-013-1058-5"},{"key":"2024010809170382000_7.2.e202302154.22","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot097899"},{"key":"2024010809170382000_7.2.e202302154.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.08.010"},{"key":"2024010809170382000_7.2.e202302154.24","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00083-07"},{"key":"2024010809170382000_7.2.e202302154.25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000922"},{"key":"2024010809170382000_7.2.e202302154.26","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-11-98"},{"key":"2024010809170382000_7.2.e202302154.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2018.02.013"},{"key":"2024010809170382000_7.2.e202302154.28","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2011.59"},{"key":"2024010809170382000_7.2.e202302154.29","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701159200"},{"key":"2024010809170382000_7.2.e202302154.30","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth1009-690"},{"key":"2024010809170382000_7.2.e202302154.31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004306"},{"key":"2024010809170382000_7.2.e202302154.32","doi-asserted-by":"publisher","DOI":"10.1101\/gad.241422.114"},{"key":"2024010809170382000_7.2.e202302154.33","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"2024010809170382000_7.2.e202302154.34","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz348"},{"key":"2024010809170382000_7.2.e202302154.35","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz1062"},{"key":"2024010809170382000_7.2.e202302154.36","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201811090"},{"key":"2024010809170382000_7.2.e202302154.37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007872"},{"key":"2024010809170382000_7.2.e202302154.38","doi-asserted-by":"publisher","DOI":"10.1016\/J.GDE.2020.10.003"},{"key":"2024010809170382000_7.2.e202302154.39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1900672116"},{"key":"2024010809170382000_7.2.e202302154.40","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw257"},{"key":"2024010809170382000_7.2.e202302154.41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005665"},{"key":"2024010809170382000_7.2.e202302154.42","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-020-02002-6"},{"key":"2024010809170382000_7.2.e202302154.43","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00188-4"},{"key":"2024010809170382000_7.2.e202302154.44","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3682"},{"key":"2024010809170382000_7.2.e202302154.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.12.006"},{"key":"2024010809170382000_7.2.e202302154.46","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1160"},{"key":"2024010809170382000_7.2.e202302154.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.12.002"},{"key":"2024010809170382000_7.2.e202302154.48","doi-asserted-by":"publisher","DOI":"10.1101\/132456"},{"key":"2024010809170382000_7.2.e202302154.49","doi-asserted-by":"publisher","DOI":"10.1101\/gr.184168.114"},{"key":"2024010809170382000_7.2.e202302154.50","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-00716-8"},{"key":"2024010809170382000_7.2.e202302154.51","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03478-4"},{"key":"2024010809170382000_7.2.e202302154.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.12.032"},{"key":"2024010809170382000_7.2.e202302154.53","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17959-y"},{"key":"2024010809170382000_7.2.e202302154.54","doi-asserted-by":"publisher","DOI":"10.1101\/gr.139469.112"},{"key":"2024010809170382000_7.2.e202302154.55","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv221"},{"key":"2024010809170382000_7.2.e202302154.56","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0114-6"},{"key":"2024010809170382000_7.2.e202302154.57","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003598"},{"key":"2024010809170382000_7.2.e202302154.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2011.09.006"},{"key":"2024010809170382000_7.2.e202302154.59","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137"},{"key":"2024010809170382000_7.2.e202302154.60","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2020.1777769"},{"key":"2024010809170382000_7.2.e202302154.61","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09320-9"}],"container-title":["Life Science Alliance"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.26508\/lsa.202302154","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T09:05:03Z","timestamp":1704877503000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.life-science-alliance.org\/lookup\/doi\/10.26508\/lsa.202302154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,21]]},"references-count":61,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,11,21]]},"published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.26508\/lsa.202302154"],"URL":"https:\/\/doi.org\/10.26508\/lsa.202302154","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.10.17.562690","asserted-by":"object"}]},"ISSN":["2575-1077"],"issn-type":[{"value":"2575-1077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,21]]}}}