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However, the relationship between the epigenetic regulatory landscape and its expression in lung cancers remains elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Circularized chromosome capture combined with sequencing (4C\u2010seq) was employed to analyze physical chromatin interactions at the <jats:italic>TBXT<\/jats:italic> loci in the lung cancer cell line H460, a high <jats:italic>TBXT\u2010expressing<\/jats:italic> cell line, compared to H358 and A549, which do not express <jats:italic>TBXT<\/jats:italic>. To define the regulatory landscape, the targeted <jats:italic>TBXT<\/jats:italic> chromatin interactions were integrated with histone modification profiles from respective cells, followed with motif analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our analysis identified distinct patterns of potential <jats:italic>cis<\/jats:italic>\u2010regulatory elements (pCREs) associated with the <jats:italic>TBXT<\/jats:italic> promoter, with increased near\u2010<jats:italic>cis<\/jats:italic> pCRE enrichment in the <jats:italic>TBXT\u2010expressing<\/jats:italic> cells. Integration of pCREs with epigenetic histone modification revealed two unique pCREs in <jats:italic>TBXT\u2010expressing<\/jats:italic> H460 cells enriched with the active histone mark H3K27ac, harboring binding sites for transcription factors of the forkhead box, zinc finger, and musculoaponeurotic fibrosarcoma families that are linked to cancer metastasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings shed light on active chromatin interactions with <jats:italic>TBXT<\/jats:italic> expression in lung cancers, pointing to specific DNA elements and regulatory proteins that may be involved. This knowledge paves the way for understanding <jats:italic>TBXT<\/jats:italic> expression dynamics at the onset and progression of metastatic cancers.<\/jats:p><\/jats:sec>","DOI":"10.1002\/gcc.70041","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T13:22:12Z","timestamp":1742304132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chromatin Interaction and Histone Mark Signatures Associated With <scp><i>TBXT<\/i><\/scp> Expression in Metastatic Lung Cancer"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4565-5903","authenticated-orcid":false,"given":"Reuben M.","family":"Yaa","sequence":"first","affiliation":[{"name":"Randall Centre for Cell &amp; Molecular Biophysics King's College London  London UK"},{"name":"UK Dementia Research Institute Imperial College London  London UK"},{"name":"Department of Brain Sciences Imperial College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian M.","family":"Schilder","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute Imperial College London  London UK"},{"name":"Department of Brain Sciences Imperial College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael D.","family":"Acemel","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo (CABD) Consejo Superior de Investigaciones Cient\u00edficas\/Universidad Pablo de Olavide  Seville Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona C.","family":"Wardle","sequence":"additional","affiliation":[{"name":"Randall Centre for Cell &amp; Molecular Biophysics King's College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_11_3_1","unstructured":"B.Bannister \u201cCancer Survival by Stage at Diagnosis for England (Experimental Statistics): Adults Diagnosed 2012 2013 and 2014 and Followed Up to 2015 With Public Health England\u201d(2016) https:\/\/backup.ons.gov.uk\/wp\u2010content\/uploads\/sites\/3\/2016\/06\/Cancer\u2010survival\u2010by\u2010stage\u2010at\u2010diagnosis\u2010for\u2010England\u2010experimental\u2010statistics\u2010Adults\u2010diagnosed\u20102012\u20102013\u2010and\u20102014\u2010.pdf."},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1016663622874"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2008.07.017"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00961"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201006\u20102353"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38379"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201011\u20103211"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3086"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434\u2010013\u20102914\u20109"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.3348"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434\u2010016\u20105530\u20107"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.208"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201013\u20101894"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2020.01.014"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13547"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010018\u20100312\u20103"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2020.100188"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1896"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2012.04.009"},{"key":"e_1_2_11_22_1","first-page":"2913","article-title":"Establishment and Identification of Small Cell Lung Cancer Cell Lines Having Classic and Variant Features","volume":"45","author":"Carney D. 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