{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:20:31Z","timestamp":1785410431036,"version":"3.56.0"},"posted":{"date-parts":[[2025,10,12]]},"group-title":"Cancer Biology","reference-count":108,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:00:00Z","timestamp":1760227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01-CA-248041"],"award-info":[{"award-number":["R01-CA-248041"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01-CA-230800"],"award-info":[{"award-number":["R01-CA-230800"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,12]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>Multiple enhancers, often located across vast genomic distances, regulate key genes. However, how chromatin topology organization at individual alleles enables cell-type-restricted multi-enhancer gene regulation remains unclear. Using acute protein degradation and time-course population-average chromatin conformation capture in lymphoma, we found that the B-cell- lineage-determining transcription factor EBF1 preferentially positions multiple enhancers at loci containing sparsely distributed genes essential for B-cell identity and oncogenesis. Our time-resolved sub-diffraction optical chromatin architecture tracing of &gt;100,000 alleles in individual lymphoma cells further revealed diverse topological conformations facilitating multi-enhancer interactions. Mechanistically, we found that positioning of enhancers at allelic topological centers is required for their interactions with target promoters, with EBF1 serving as a barrier to the loop-extruding cohesin on enhancers. These findings, which we demonstrate their generalizability to the T-cell-lineage-determining transcription factor TCF1 in T-cell leukemia, suggest that lineage-determining transcription factors radially position enhancers and promoters to enable multi-enhancer regulation of key oncogenes.<\/jats:p>","DOI":"10.1101\/2025.10.10.681717","type":"posted-content","created":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T20:15:14Z","timestamp":1760300114000},"source":"Crossref","is-referenced-by-count":0,"title":["Lineage-determining transcription factors constrain cohesin to drive multi-enhancer oncogene regulation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9422-6902","authenticated-orcid":false,"given":"Yeqiao","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3739-6726","authenticated-orcid":false,"given":"Atishay","family":"Jay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Burget","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4014-8678","authenticated-orcid":false,"given":"Tobias","family":"Friedrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0107-0057","authenticated-orcid":false,"given":"Sora","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8558-6471","authenticated-orcid":false,"given":"Jessica","family":"Alsing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9268-6596","authenticated-orcid":false,"given":"Guy","family":"Nir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0058-1250","authenticated-orcid":false,"given":"Rudolf","family":"Grosschedl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2249-8247","authenticated-orcid":false,"given":"Golnaz","family":"Vahedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7931-2175","authenticated-orcid":false,"given":"Robert B.","family":"Faryabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025101412151417000_2025.10.10.681717v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12644"},{"key":"2025101412151417000_2025.10.10.681717v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12716"},{"key":"2025101412151417000_2025.10.10.681717v1.3","doi-asserted-by":"publisher","DOI":"10.1101\/sqb.2015.80.027219"},{"key":"2025101412151417000_2025.10.10.681717v1.4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.7.080505.115623"},{"key":"2025101412151417000_2025.10.10.681717v1.5","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-120423-012301"},{"key":"2025101412151417000_2025.10.10.681717v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0209-0"},{"key":"2025101412151417000_2025.10.10.681717v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52375-6"},{"key":"2025101412151417000_2025.10.10.681717v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0128-0"},{"key":"2025101412151417000_2025.10.10.681717v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112068"},{"key":"2025101412151417000_2025.10.10.681717v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3963"},{"key":"2025101412151417000_2025.10.10.681717v1.11","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau0320"},{"key":"2025101412151417000_2025.10.10.681717v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.01.012"},{"key":"2025101412151417000_2025.10.10.681717v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.03.035"},{"key":"2025101412151417000_2025.10.10.681717v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.09.053"},{"key":"2025101412151417000_2025.10.10.681717v1.15","doi-asserted-by":"publisher","DOI":"10.1126\/science.1230184"},{"key":"2025101412151417000_2025.10.10.681717v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3207"},{"key":"2025101412151417000_2025.10.10.681717v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2014.02.009"},{"key":"2025101412151417000_2025.10.10.681717v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1182-7"},{"key":"2025101412151417000_2025.10.10.681717v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.05.004"},{"key":"2025101412151417000_2025.10.10.681717v1.20","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12037"},{"key":"2025101412151417000_2025.10.10.681717v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.048"},{"key":"2025101412151417000_2025.10.10.681717v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/J.MOLCEL.2020.03.002"},{"key":"2025101412151417000_2025.10.10.681717v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3999"},{"key":"2025101412151417000_2025.10.10.681717v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.01.003"},{"key":"2025101412151417000_2025.10.10.681717v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.11.021"},{"key":"2025101412151417000_2025.10.10.681717v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.11.037"},{"key":"2025101412151417000_2025.10.10.681717v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.01.006"},{"key":"2025101412151417000_2025.10.10.681717v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.07.030"},{"key":"2025101412151417000_2025.10.10.681717v1.29","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adl4043"},{"key":"2025101412151417000_2025.10.10.681717v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2019.12.010"},{"key":"2025101412151417000_2025.10.10.681717v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-00478-x"},{"key":"2025101412151417000_2025.10.10.681717v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.03.009"},{"key":"2025101412151417000_2025.10.10.681717v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01641-2"},{"key":"2025101412151417000_2025.10.10.681717v1.34","doi-asserted-by":"publisher","DOI":"10.1038\/nature12753"},{"key":"2025101412151417000_2025.10.10.681717v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.026"},{"key":"2025101412151417000_2025.10.10.681717v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01223-8"},{"key":"2025101412151417000_2025.10.10.681717v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.01.029"},{"key":"2025101412151417000_2025.10.10.681717v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/J.IMMUNI.2016.02.021"},{"key":"2025101412151417000_2025.10.10.681717v1.39","doi-asserted-by":"publisher","DOI":"10.1101\/gad.176826.111"},{"key":"2025101412151417000_2025.10.10.681717v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01232-z"},{"key":"2025101412151417000_2025.10.10.681717v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0390-6"},{"key":"2025101412151417000_2025.10.10.681717v1.42","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-0602-9"},{"key":"2025101412151417000_2025.10.10.681717v1.43","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-100024"},{"key":"2025101412151417000_2025.10.10.681717v1.44","doi-asserted-by":"publisher","DOI":"10.1038\/376263a0"},{"key":"2025101412151417000_2025.10.10.681717v1.45","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-008-8043-z"},{"key":"2025101412151417000_2025.10.10.681717v1.46","doi-asserted-by":"publisher","DOI":"10.1038\/ni0710-572"},{"key":"2025101412151417000_2025.10.10.681717v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.06.010"},{"key":"2025101412151417000_2025.10.10.681717v1.48","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2641"},{"key":"2025101412151417000_2025.10.10.681717v1.49","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-018-0021-8"},{"key":"2025101412151417000_2025.10.10.681717v1.50","doi-asserted-by":"publisher","DOI":"10.1101\/gad.309583.117"},{"key":"2025101412151417000_2025.10.10.681717v1.51","doi-asserted-by":"publisher","DOI":"10.1038\/ng1966"},{"key":"2025101412151417000_2025.10.10.681717v1.52","doi-asserted-by":"publisher","DOI":"10.1038\/47412"},{"key":"2025101412151417000_2025.10.10.681717v1.53","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5373.60"},{"key":"2025101412151417000_2025.10.10.681717v1.54","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1891"},{"key":"2025101412151417000_2025.10.10.681717v1.55","doi-asserted-by":"publisher","DOI":"10.1038\/nature11049"},{"key":"2025101412151417000_2025.10.10.681717v1.56","doi-asserted-by":"publisher","DOI":"10.1038\/nature11082"},{"key":"2025101412151417000_2025.10.10.681717v1.57","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01871-y"},{"key":"2025101412151417000_2025.10.10.681717v1.58","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18013-7"},{"key":"2025101412151417000_2025.10.10.681717v1.59","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03144-y"},{"key":"2025101412151417000_2025.10.10.681717v1.60","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2828"},{"key":"2025101412151417000_2025.10.10.681717v1.61","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00645"},{"key":"2025101412151417000_2025.10.10.681717v1.62","doi-asserted-by":"publisher","DOI":"10.1038\/ni1555"},{"key":"2025101412151417000_2025.10.10.681717v1.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.09.066"},{"key":"2025101412151417000_2025.10.10.681717v1.64","unstructured":"Zhou Y , Sheng Y , Faryabi RB. Optical Looping Interactive Viewing Engine (OLIVE) https:\/\/faryabilab.github.io\/chromatin-traces-vis\/2025."},{"key":"2025101412151417000_2025.10.10.681717v1.65","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.11.008"},{"key":"2025101412151417000_2025.10.10.681717v1.66","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1317788111"},{"key":"2025101412151417000_2025.10.10.681717v1.67","doi-asserted-by":"publisher","DOI":"10.1038\/nature06634"},{"key":"2025101412151417000_2025.10.10.681717v1.68","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2210480120"},{"key":"2025101412151417000_2025.10.10.681717v1.69","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1518552112"},{"key":"2025101412151417000_2025.10.10.681717v1.70","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.072"},{"key":"2025101412151417000_2025.10.10.681717v1.71","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.09.003"},{"key":"2025101412151417000_2025.10.10.681717v1.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.01.015"},{"key":"2025101412151417000_2025.10.10.681717v1.73","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-068478"},{"key":"2025101412151417000_2025.10.10.681717v1.74","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-02-409839"},{"key":"2025101412151417000_2025.10.10.681717v1.75","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbior.2019.100639"},{"key":"2025101412151417000_2025.10.10.681717v1.76","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a000588"},{"key":"2025101412151417000_2025.10.10.681717v1.77","doi-asserted-by":"publisher","DOI":"10.1038\/nature21411"},{"key":"2025101412151417000_2025.10.10.681717v1.78","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2023.07.017"},{"key":"2025101412151417000_2025.10.10.681717v1.79","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.08.006"},{"key":"2025101412151417000_2025.10.10.681717v1.80","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.068"},{"key":"2025101412151417000_2025.10.10.681717v1.81","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01391-1"},{"key":"2025101412151417000_2025.10.10.681717v1.82","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau1783"},{"key":"2025101412151417000_2025.10.10.681717v1.83","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007872"},{"key":"2025101412151417000_2025.10.10.681717v1.84","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2023.102175"},{"key":"2025101412151417000_2025.10.10.681717v1.85","doi-asserted-by":"publisher","DOI":"10.1242\/dev.182766"},{"key":"2025101412151417000_2025.10.10.681717v1.86","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.10.009"},{"key":"2025101412151417000_2025.10.10.681717v1.87","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar3958"},{"key":"2025101412151417000_2025.10.10.681717v1.88","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01599-7"},{"key":"2025101412151417000_2025.10.10.681717v1.89","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao0932"},{"key":"2025101412151417000_2025.10.10.681717v1.90","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2688"},{"key":"2025101412151417000_2025.10.10.681717v1.91","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3170"},{"key":"2025101412151417000_2025.10.10.681717v1.92","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1714530115"},{"key":"2025101412151417000_2025.10.10.681717v1.93","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.07.032"},{"key":"2025101412151417000_2025.10.10.681717v1.94","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"2025101412151417000_2025.10.10.681717v1.95","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137"},{"key":"2025101412151417000_2025.10.10.681717v1.96","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2025101412151417000_2025.10.10.681717v1.97","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"2025101412151417000_2025.10.10.681717v1.98","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu379"},{"key":"2025101412151417000_2025.10.10.681717v1.99","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq351"},{"key":"2025101412151417000_2025.10.10.681717v1.100","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2016.07.002"},{"key":"2025101412151417000_2025.10.10.681717v1.101","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0831-x"},{"key":"2025101412151417000_2025.10.10.681717v1.102","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv336"},{"key":"2025101412151417000_2025.10.10.681717v1.103","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz540"},{"key":"2025101412151417000_2025.10.10.681717v1.104","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1012067"},{"key":"2025101412151417000_2025.10.10.681717v1.105","doi-asserted-by":"publisher","DOI":"10.1088\/1742-5468\/2008\/10\/P10008"},{"key":"2025101412151417000_2025.10.10.681717v1.106","doi-asserted-by":"publisher","DOI":"10.1093\/nargab\/lqab040"},{"key":"2025101412151417000_2025.10.10.681717v1.107","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2025101412151417000_2025.10.10.681717v1.108","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2015.09.004"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.10.10.681717","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:00:11Z","timestamp":1782277211000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.10.10.681717"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,12]]},"references-count":108,"URL":"https:\/\/doi.org\/10.1101\/2025.10.10.681717","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1038\/s41556-025-01827-2","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,10,12]]},"subtype":"preprint"}}