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dc.contributor.authorD'Oto, Alexandra
dc.contributor.authorFang, Jie
dc.contributor.authorJin, Hongjian
dc.contributor.authorXu, Beisi
dc.contributor.authorSingh, Shivendra
dc.contributor.authorMullasseril, Anoushka
dc.contributor.authorJones, Victoria
dc.contributor.authorAbu-Zaid, Ahmed
dc.contributor.authorvon Buttlar, Xinyu
dc.contributor.authorCooke, Bailey
dc.contributor.authorHu, Dongli
dc.contributor.authorShohet, Jason
dc.contributor.authorMurphy, Andrew J
dc.contributor.authorDavidoff, Andrew M
dc.contributor.authorYang, Jun
dc.date.accessioned2023-04-25T13:39:01Z
dc.date.available2023-04-25T13:39:01Z
dc.date.issued2021-12-10
dc.identifier.citationD'Oto A, Fang J, Jin H, Xu B, Singh S, Mullasseril A, Jones V, Abu-Zaid A, von Buttlar X, Cooke B, Hu D, Shohet J, Murphy AJ, Davidoff AM, Yang J. KDM6B promotes activation of the oncogenic CDK4/6-pRB-E2F pathway by maintaining enhancer activity in MYCN-amplified neuroblastoma. Nat Commun. 2021 Dec 10;12(1):7204. doi: 10.1038/s41467-021-27502-2. PMID: 34893606; PMCID: PMC8664842.en_US
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/s41467-021-27502-2en_US
dc.identifier.pmid34893606
dc.identifier.urihttp://hdl.handle.net/20.500.14038/51984
dc.description.abstractThe H3K27me2/me3 histone demethylase KDM6B is essential to neuroblastoma cell survival. However, the mechanism of KDM6B action remains poorly defined. We demonstrate that inhibition of KDM6B activity 1) reduces the chromatin accessibility of E2F target genes and MYCN, 2) selectively leads to an increase of H3K27me3 but a decrease of the enhancer mark H3K4me1 at the CTCF and BORIS binding sites, which may, consequently, disrupt the long-range chromatin interaction of MYCN and E2F target genes, and 3) phenocopies the transcriptome induced by the specific CDK4/6 inhibitor palbociclib. Overexpression of CDK4/6 or Rb1 knockout confers neuroblastoma cell resistance to both palbociclib and the KDM6 inhibitor GSK-J4. These data indicate that KDM6B promotes an oncogenic CDK4/6-pRB-E2F pathway in neuroblastoma cells via H3K27me3-dependent enhancer-promoter interactions, providing a rationale to target KDM6B for high-risk neuroblastoma.en_US
dc.language.isoenen_US
dc.relation.ispartofNature Communicationsen_US
dc.relation.urlhttps://doi.org/10.1038/s41467-021-27502-2en_US
dc.rightsOpen Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. © The Author(s) 2021en_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectCanceren_US
dc.subjectChemical biologyen_US
dc.titleKDM6B promotes activation of the oncogenic CDK4/6-pRB-E2F pathway by maintaining enhancer activity in MYCN-amplified neuroblastomaen_US
dc.typeJournal Articleen_US
dc.source.journaltitleNature communications
dc.source.volume12
dc.source.issue1
dc.source.beginpage7204
dc.source.endpage
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryEngland
dc.identifier.journalNature communications
refterms.dateFOA2023-04-25T13:39:02Z
dc.contributor.departmentPediatricsen_US


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Open Access: This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use, sharing,
adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative
Commons license, and indicate if changes were made. The images or other third party
material in this article are included in the article’s Creative Commons license, unless
indicated otherwise in a credit line to the material. If material is not included in the
article’s Creative Commons license and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from
the copyright holder. To view a copy of this license, visit http://creativecommons.org/
licenses/by/4.0/.
© The Author(s) 2021
Except where otherwise noted, this item's license is described as Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. © The Author(s) 2021