{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:45:07Z","timestamp":1789771507270,"version":"4.0.1"},"reference-count":183,"publisher":"Oxford University Press (OUP)","issue":"19","license":[{"start":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:00:00Z","timestamp":1695340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FRN PJT153186"],"award-info":[{"award-number":["FRN PJT153186"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT180312"],"award-info":[{"award-number":["PJT180312"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015668","name":"Ontario Ministry of Research and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015668","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Enhancer reprogramming has been proposed as a key source of transcriptional dysregulation during tumorigenesis, but the molecular mechanisms underlying this process remain unclear. Here, we identify an enhancer cluster required for normal development that is aberrantly activated in breast and lung adenocarcinoma. Deletion of the SRR124\u2013134 cluster disrupts expression of the SOX2 oncogene, dysregulates genome-wide transcription and chromatin accessibility and reduces the ability of cancer cells to form colonies in vitro. Analysis of primary tumors reveals a correlation between chromatin accessibility at this cluster and SOX2 overexpression in breast and lung cancer patients. We demonstrate that FOXA1 is an activator and NFIB is a repressor of SRR124\u2013134 activity and SOX2 transcription in cancer cells, revealing a co-opting of the regulatory mechanisms involved in early development. Notably, we show that the conserved SRR124 and SRR134 regions are essential during mouse development, where homozygous deletion results in the lethal failure of esophageal\u2013tracheal separation. These findings provide insights into how developmental enhancers can be reprogrammed during tumorigenesis and underscore the importance of understanding enhancer dynamics during development and disease.<\/jats:p>","DOI":"10.1093\/nar\/gkad734","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T19:59:50Z","timestamp":1692907190000},"page":"10109-10131","source":"Crossref","is-referenced-by-count":22,"title":["Epigenetic reprogramming of a distal developmental enhancer cluster drives\n                    <i>SOX2<\/i>\n                    overexpression in breast and lung adenocarcinoma"],"prefix":"10.1093","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1051-7997","authenticated-orcid":false,"given":"Luis E","family":"Abatti","sequence":"first","affiliation":[{"name":"Department of Cell and Systems Biology, University of Toronto , Toronto , Ontario , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Lado-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Senescence, Cancer and Aging, Health Research Institute of Santiago de Compostela (IDIS), Xerencia de Xesti\u00f3n Integrada de Santiago (XXIS\/SERGAS) , Santiago de Compostela , Spain"},{"name":"Department of Physiology and Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela , Santiago de Compostela , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linh","family":"Huynh","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network , Toronto , Ontario , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Collado","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Senescence, Cancer and Aging, Health Research Institute of Santiago de Compostela (IDIS), Xerencia de Xesti\u00f3n Integrada de Santiago (XXIS\/SERGAS) , Santiago de Compostela , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4517-1562","authenticated-orcid":false,"given":"Michael\u00a0M","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network , Toronto , Ontario , Canada"},{"name":"Department of Medical Biophysics, University of Toronto , Toronto , Ontario , Canada"},{"name":"Department of Computer Science, University of Toronto , Toronto , Ontario , Canada"},{"name":"Vector Institute for Artificial Intelligence , Toronto , Ontario , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7147-4604","authenticated-orcid":false,"given":"Jennifer\u00a0A","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Cell and Systems Biology, University of Toronto , Toronto , Ontario , Canada"},{"name":"Laboratory Medicine and Pathobiology, University of Toronto , Toronto , Ontario , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,9,22]]},"reference":[{"key":"2023102701520825400_B1","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.cell.2012.12.033","article-title":"Genome-wide chromatin state transitions associated with developmental and environmental cues","volume":"152","author":"Zhu","year":"2013","journal-title":"Cell"},{"key":"2023102701520825400_B2","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.stem.2010.03.018","article-title":"Distinct epigenomic landscapes of pluripotent and lineage-committed human cells","volume":"6","author":"Hawkins","year":"2010","journal-title":"Cell Stem Cell"},{"key":"2023102701520825400_B3","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nature09692","article-title":"A unique chromatin signature uncovers early developmental enhancers in humans","volume":"470","author":"Rada-Iglesias","year":"2011","journal-title":"Nature"},{"key":"2023102701520825400_B4","doi-asserted-by":"crossref","first-page":"21931","DOI":"10.1073\/pnas.1016071107","article-title":"Histone H3K27ac separates active from poised enhancers and predicts developmental state","volume":"107","author":"Creyghton","year":"2010","journal-title":"Proc. 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