{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T22:24:31Z","timestamp":1789943071624,"version":"4.0.1"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"13","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,8,18]]},"abstract":"<jats:p>Regulation of lineage-restricted transcription factors has been shown to influence malignant transformation in several types of cancer. Whether similar mechanisms are involved in ovarian cancer pathogenesis is unknown. PAX8 is a nuclear transcription factor that controls the embryologic development of the M\u00fcllerian system, including the fallopian tubes. Recent studies have shown that fallopian tube secretory epithelial cells (FTSECs) give rise to the most common form of ovarian cancer, high-grade serous ovarian carcinomas (HGSOCs). We designed the present study in order to understand whether changes in gene expression between FTSECs and HGSOCs relate to alterations in PAX8 binding to chromatin. Using whole transcriptome shotgun sequencing (RNA-Seq) after PAX8 knockdown and ChIP-Seq, we show that FTSECs and HGSOCs are distinguished by marked reprogramming of the PAX8 cistrome. Genes that are significantly altered between FTSECs and HGSOCs are enriched near PAX8 binding sites. These sites are also near TEAD binding sites, and these transcriptional changes may be related to PAX8 interactions with the TEAD\/YAP1 signaling pathway. These data suggest that transcriptional changes after transformation in ovarian cancer are closely related to epigenetic remodeling in lineage-specific transcription factors.<\/jats:p>","DOI":"10.1172\/jci.insight.87988","type":"journal-article","created":{"date-parts":[[2016,8,17]],"date-time":"2016-08-17T11:01:00Z","timestamp":1471431660000},"source":"Crossref","is-referenced-by-count":44,"title":["Epigenetic remodeling regulates transcriptional changes between ovarian cancer and benign precursors"],"prefix":"10.1172","volume":"1","author":[{"given":"Kevin M.","family":"Elias","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."},{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."},{"name":"Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan M.","family":"Emori","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."},{"name":"Graduate School of Arts and Sciences, Harvard University, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Westerling","sequence":"additional","affiliation":[{"name":"Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Long","sequence":"additional","affiliation":[{"name":"Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Budina-Kolomets","sequence":"additional","affiliation":[{"name":"Penn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fugen","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"MacDuffie","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle R.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."},{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."},{"name":"Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Holman","sequence":"additional","affiliation":[{"name":"Computational Biology and Functional Genomics Laboratory, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Lawney","sequence":"additional","affiliation":[{"name":"Computational Biology and Functional Genomics Laboratory, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew L.","family":"Freedman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."},{"name":"Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."},{"name":"Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2702-5879","authenticated-orcid":true,"given":"John","family":"Quackenbush","sequence":"additional","affiliation":[{"name":"Computational Biology and Functional Genomics Laboratory, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myles","family":"Brown","sequence":"additional","affiliation":[{"name":"Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6912-6977","authenticated-orcid":true,"given":"Ronny","family":"Drapkin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA."},{"name":"Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Penn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2016,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.05.008"},{"issue":"3","key":"B2","doi-asserted-by":"crossref","first-page":"641","DOI":"10.3390\/genes6030641","article-title":"Chromatin Dynamics in Lineage Commitment and Cellular Reprogramming","volume":"6","author":"Shchuka","year":"2015","journal-title":"Genes (Basel)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002688"},{"key":"B4","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.06857.025","article-title":"Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells","author":"Laurette","year":"2015","journal-title":"Elife"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nature09409"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00762-6"},{"issue":"7257","key":"B7","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/nature08210","article-title":"A role for Lin28 in primordial germ-cell development and germ-cell malignancy","volume":"460","author":"West","year":"2009","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e318216c112"},{"issue":"5","key":"B9","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1097\/PAS.0b013e3181da7687","article-title":"PAX8 reliably distinguishes ovarian serous tumors from malignant mesothelioma","volume":"34","author":"Laury","year":"2010","journal-title":"Am J Surg Pathol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-1054"},{"issue":"5","key":"B11","first-page":"296","article-title":"The role of the fallopian tube in ovarian cancer","volume":"10","author":"Tone","year":"2012","journal-title":"Clin Adv Hematol Oncol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181868904"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-1382"},{"key":"B14","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2013.00217","article-title":"Modeling High-Grade Serous Carcinoma: How Converging Insights into Pathogenesis and Genetics are Driving Better Experimental Platforms","volume":"3","author":"Jones","year":"2013","journal-title":"Front Oncol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017300108"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.402"},{"issue":"6","key":"B17","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.ccr.2013.10.013","article-title":"Transformation of the fallopian tube secretory epithelium leads to high-grade serous ovarian cancer in Brca;Tp53;Pten models","volume":"24","author":"Perets","year":"2013","journal-title":"Cancer Cell"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2015.08.017"},{"key":"B19","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms3126","article-title":"Evaluating cell lines as tumour models by comparison of genomic profiles","volume":"4","author":"Domcke","year":"2013","journal-title":"Nat Commun"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072162"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2015.05.040"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.288"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.097"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1109363108"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-8-r83"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003043200"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90818-4"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90516-7"},{"issue":"7 Suppl","key":"B29","first-page":"1707s","article-title":"Pax genes and their role in organogenesis","volume":"59","author":"Mansouri","year":"1999","journal-title":"Cancer Res"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90434-Z"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.10.2048"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(96)80087-1"},{"key":"B33","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2407-14-292","article-title":"A role for PAX8 in the tumorigenic phenotype of ovarian cancer cells","volume":"14","author":"Di Palma","year":"2014","journal-title":"BMC Cancer"},{"key":"B34","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2164-13-147","article-title":"Genome-wide analysis of Pax8 binding provides new insights into thyroid functions","volume":"13","author":"Ruiz-Llorente","year":"2012","journal-title":"BMC Genomics"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1593\/neo.91542"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.562"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3924"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/nature11979"},{"key":"B39","article-title":"High Expressions of Lgr5 and ALDH1 in Primary Epithelial Ovarian Cancer Correlate with Advanced Tumor Stage and Grade as well as Poor Prognosis of the Patients","author":"Sun","journal-title":"Gynecol Obstet Invest"},{"issue":"147","key":"B40","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3003778","article-title":"Targeted tumor-penetrating siRNA nanocomplexes for credentialing the ovarian cancer oncogene ID4","volume":"4","author":"Ren","year":"2012","journal-title":"Sci Transl Med"},{"issue":"3","key":"B41","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1160\/TH08-01-0052","article-title":"Expression and prognostic significance of kallikrein-related peptidase 8 protein levels in advanced ovarian cancer by using automated quantitative analysis","volume":"101","author":"Kountourakis","year":"2009","journal-title":"Thromb Haemost"},{"issue":"4","key":"B42","first-page":"806","article-title":"The human KLK8 (neuropsin\/ovasin) gene: identification of two novel splice variants and its prognostic value in ovarian cancer","volume":"7","author":"Magklara","year":"2001","journal-title":"Clin Cancer Res"},{"issue":"2","key":"B43","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/ng.3470","article-title":"Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers","volume":"48","author":"Zhang","year":"2016","journal-title":"Nat Genet"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2015.05.002"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/nature15518"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3216"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005465"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4085"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-10-r106"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.016"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/87988\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T14:22:35Z","timestamp":1779200555000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/87988"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,18]]},"references-count":50,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2016,8,18]]},"published-print":{"date-parts":[[2016,8,18]]}},"alternative-id":["10.1172\/jci.insight.87988"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.87988","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,18]]},"article-number":"e87988"}}