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dc.contributor.authorBojang, Pasano, Jr.
dc.contributor.authorRamos, Kenneth S.
dc.date.accessioned2018-12-05T23:30:46Z
dc.date.available2018-12-05T23:30:46Z
dc.date.issued2018-08
dc.identifier.citationBojang, P. and Ramos, K. S. (2018), Epigenetic reactivation of LINE‐1 retrotransposon disrupts NuRD corepressor functions and induces oncogenic transformation in human bronchial epithelial cells. Mol Oncol, 12: 1342-1357. doi:10.1002/1878-0261.12329en_US
dc.identifier.pmid29845737
dc.identifier.doi10.1002/1878-0261.12329
dc.identifier.urihttp://hdl.handle.net/10150/631126
dc.description.abstractLong interspersed nuclear element-1 (LINE-1 or L1) reactivation is linked to poor prognosis in non-small-cell lung carcinoma (NSCLC), but the molecular bases of this response remain largely unknown. In this report, we show that challenge of human bronchial epithelial cells (HBECs) with the lung carcinogen, benzo(a)pyrene (BaP), shifted the L1 promoter from a heterochromatic to euchromatic state through disassembly of the nucleosomal and remodeling deacetylase (NuRD) complex. Carcinogen challenge was also associated with partial displacement of constituent proteins from the nuclear to the cytoplasmic compartment. Disruption of NuRD corepression by genetic ablation or carcinogen treatment correlated with accumulation of L1 mRNA and proteins. Mi2 bound directly to the L1 promoter to effect retroelement silencing, and this response required the DNA- and ATPase-binding domains of Mi2. Sustained expression of L1 in HBECs was tumorigenic in a human-SCID mouse xenograft model, giving rise to tumors that regressed over time. Together, these results show that functional modulation of the NuRD constituent proteins is a critical molecular event in the activation of L1 retrotransposon. L1 expression creates a microenvironment in HBECs that is conducive to neoplasia and malignant transformation.en_US
dc.description.sponsorshipUniversity of Arizona Health Sciences [P30 CA023074]en_US
dc.language.isoenen_US
dc.publisherWILEYen_US
dc.relation.urlhttps://febs.onlinelibrary.wiley.com/doi/full/10.1002/1878-0261.12329en_US
dc.rights© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License.en_US
dc.subjectbenzo(a)pyreneen_US
dc.subjecteuchromatinen_US
dc.subjectheterochromatinen_US
dc.subjectlong interspersed nuclear element-1en_US
dc.subjectnucleosomal and remodeling deacetylase complexen_US
dc.subjectretrotransposonen_US
dc.titleEpigenetic reactivation of LINE-1 retrotransposon disrupts NuRD corepressor functions and induces oncogenic transformation in human bronchial epithelial cellsen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Coll Med, Div Pulm Allergy Crit Care & Sleep Meden_US
dc.contributor.departmentUniv Arizona Hlth Sci, Ctr Appl Genet & Genom Meden_US
dc.identifier.journalMOLECULAR ONCOLOGYen_US
dc.description.noteOpen access journal.en_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
refterms.dateFOA2018-12-05T23:30:47Z


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