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dc.contributor.authorDries, Ruben
dc.contributor.authorSeruggia, Davide
dc.contributor.authorGao, Yang
dc.contributor.authorSharma, Bandana
dc.contributor.authorHuang, Hao
dc.contributor.authorMoreau, Lisa
dc.contributor.authorMcLane, Michael
dc.contributor.authorMarco, Eugenio
dc.contributor.authorChen, Ting
dc.contributor.authorYuan, Guo-Cheng
dc.contributor.authorYoung, Richard A.
dc.contributor.authorDebruyne, David
dc.contributor.authorDay, Daniel
dc.contributor.authorGray, Nathanael
dc.contributor.authorWong, Kwok-Kin
dc.contributor.authorOrkin, Stuart
dc.contributor.authorGeorge, Rani
dc.contributor.authorSengupta, Satyaki
dc.date.accessioned2020-01-22T14:40:02Z
dc.date.issued2019-08
dc.identifier.citationDebruyne, David N., Ruben Dries, Satyaki Sengupta, Davide Seruggia, Yang Gao, Bandana Sharma, Hao Huang, Lisa Moreau, Michael Mclane, Daniel S. Day, Eugenio Marco, Ting Chen, Nathanael S. Gray, Kwok-Kin Wong, Stuart H. Orkin, Guo-Cheng Yuan, Richard A. Young, and Rani E. George. 2019. BORIS Promotes Chromatin Regulatory Interactions in Treatment-resistant Cancer Cells. Nature 572, no. 7771: 676-680.en_US
dc.identifier.issn0028-0836en_US
dc.identifier.issn1476-4687en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:42219239*
dc.description.abstractThe CCCTC-binding factor (CTCF), which anchors DNA loops that organize the genome into structural domains, plays a central role in gene control by facilitating or constraining interactions between genes and their regulatory elements. In cancer cells the disruption of CTCF binding at specific loci through somatic mutation or DNA hypermethylation5 results in the loss of loop anchors and consequent activation of oncogenes. By contrast, the germ cell-specific paralog of CTCF, BORIS (Brother of the Regulator of Imprinted Sites), is overexpressed in multiple cancers, but its contributions to the malignant phenotype remain unclear. Here we show that aberrant upregulation of BORIS promotes novel chromatin interactions in ALK-mutated, MYCN-amplified neuroblastoma cells rendered resistant to ALK inhibition. These cells are reprogrammed to a distinct phenotypic state during the acquisition of resistance, a process defined by the initial loss of MYCN expression followed by subsequent overexpression of BORIS and a concomitant switch in cellular dependence from MYCN to BORIS. The resultant BORIS-regulated alterations in chromatin looping lead to the formation of new super-enhancers that drive the ectopic expression of a subset of proneural transcription factors that ultimately define the resistance phenotype. These results identify a previously unrecognized role of BORIS – to engender regulatory chromatin interactions that support specific cancer phenotypes.en_US
dc.language.isoen_USen_US
dc.publisherSpringer Science and Business Media LLCen_US
dc.relationNatureen_US
dash.licenseLAA
dc.subjectMultidisciplinaryen_US
dc.titleBORIS Promotes Chromatin Regulatory Interactions in Treatment-Resistant Cancer Cellsen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalNatureen_US
dash.depositing.authorGeorge, Rani
dash.waiver2019-06-20
dc.date.available2020-01-22T14:40:02Z
dash.affiliation.otherHarvard Medical Schoolen_US
dc.identifier.doi10.1038/s41586-019-1472-0
dc.source.journalNature
dash.waiver.reasonApparently the open access policy is incompatible with the business model for the journal.en_US
dash.source.volume572;7771
dash.source.page676-680
dash.contributor.affiliatedDebruyne, David
dash.contributor.affiliatedGao, Yang
dash.contributor.affiliatedDries, Ruben
dash.contributor.affiliatedHuang, Hao
dash.contributor.affiliatedSeruggia, Davide
dash.contributor.affiliatedYuan, Guo-Cheng
dash.contributor.affiliatedMoreau, Lisa
dash.contributor.affiliatedDay, Daniel
dash.contributor.affiliatedGeorge, Rani
dash.contributor.affiliatedGray, Nathanael
dash.contributor.affiliatedChen, Ting
dash.contributor.affiliatedOrkin, Stuart


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