Epigenetic reactivation of LINE-1 retrotransposon disrupts NuRD corepressor functions and induces oncogenic transformation in human bronchial epithelial cells
AffiliationUniv Arizona, Coll Med, Div Pulm Allergy Crit Care & Sleep Med
Univ Arizona Hlth Sci, Ctr Appl Genet & Genom Med
long interspersed nuclear element-1
nucleosomal and remodeling deacetylase complex
MetadataShow full item record
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:10.1002/1878-0261.12329
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.
Collection InformationThis 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 firstname.lastname@example.org.
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.
NoteOpen access journal.
VersionFinal published version
SponsorsUniversity of Arizona Health Sciences [P30 CA023074]
- LINE-1 silencing by retinoblastoma proteins is effected through the nucleosomal and remodeling deacetylase multiprotein complex.
- Authors: Montoya-Durango DE, Ramos KA, Bojang P, Ruiz L, Ramos IN, Ramos KS
- Issue date: 2016 Jan 25
- Reactivation of L1 retrotransposon by benzo(a)pyrene involves complex genetic and epigenetic regulation.
- Authors: Teneng I, Montoya-Durango DE, Quertermous JL, Lacy ME, Ramos KS
- Issue date: 2011 Mar
- Epigenetic control of mammalian LINE-1 retrotransposon by retinoblastoma proteins.
- Authors: Montoya-Durango DE, Liu Y, Teneng I, Kalbfleisch T, Lacy ME, Steffen MC, Ramos KS
- Issue date: 2009 Jun 1
- The aryl hydrocarbon receptor agonist benzo(a)pyrene reactivates LINE-1 in HepG2 cells through canonical TGF-β1 signaling: implications in hepatocellular carcinogenesis.
- Authors: Reyes-Reyes EM, Ramos IN, Tavera-Garcia MA, Ramos KS
- Issue date: 2016
- Activation of human long interspersed nuclear element 1 retrotransposition by benzo(a)pyrene, an ubiquitous environmental carcinogen.
- Authors: Stribinskis V, Ramos KS
- Issue date: 2006 Mar 1