Epigenetic reactivation of LINE-1 retrotransposon disrupts NuRD corepressor functions and induces oncogenic transformation in human bronchial epithelial cells
dc.contributor.author | Bojang, Pasano, Jr. | |
dc.contributor.author | Ramos, Kenneth S. | |
dc.date.accessioned | 2018-12-05T23:30:46Z | |
dc.date.available | 2018-12-05T23:30:46Z | |
dc.date.issued | 2018-08 | |
dc.identifier.citation | Bojang, 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:10.1002/1878-0261.12329 | en_US |
dc.identifier.pmid | 29845737 | |
dc.identifier.doi | 10.1002/1878-0261.12329 | |
dc.identifier.uri | http://hdl.handle.net/10150/631126 | |
dc.description.abstract | Long 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.sponsorship | University of Arizona Health Sciences [P30 CA023074] | en_US |
dc.language.iso | en | en_US |
dc.publisher | WILEY | en_US |
dc.relation.url | https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1878-0261.12329 | en_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.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.subject | benzo(a)pyrene | en_US |
dc.subject | euchromatin | en_US |
dc.subject | heterochromatin | en_US |
dc.subject | long interspersed nuclear element-1 | en_US |
dc.subject | nucleosomal and remodeling deacetylase complex | en_US |
dc.subject | retrotransposon | en_US |
dc.title | Epigenetic reactivation of LINE-1 retrotransposon disrupts NuRD corepressor functions and induces oncogenic transformation in human bronchial epithelial cells | en_US |
dc.type | Article | en_US |
dc.contributor.department | Univ Arizona, Coll Med, Div Pulm Allergy Crit Care & Sleep Med | en_US |
dc.contributor.department | Univ Arizona Hlth Sci, Ctr Appl Genet & Genom Med | en_US |
dc.identifier.journal | MOLECULAR ONCOLOGY | en_US |
dc.description.note | Open access journal. | en_US |
dc.description.collectioninformation | This 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.version | Final published version | en_US |
refterms.dateFOA | 2018-12-05T23:30:47Z |