Epigenetic Control of Embryonic Renal Cell Differentiation by L1 Retrotransposon

Overview

Journal Birth Defects Res A Clin Mol Teratol

Publisher Wiley

Date 2011 Mar 9

PMID 21384534

Citations 7

Authors

Kenneth S Ramos

Diego E Montoya-Durango

Ivo Teneng

Adrian Nanez

Vilius Stribinskis

Affiliations

Soon will be listed here.

Abstract

Background: L1 retroelements may play a central role in morphogenesis through epigenetic mechanisms involving recruitment of chromatin modifying protein complexes. Retroelements are repressed in terminally differentiated cells, and highly active in embryonic, undifferentiated, and transformed cells. It is not clear if the modulation of differentiation by L1 is a "cause" or "effect". The purpose of this study was to determine if murine embryonic kidney cells of clonal origin (mK4 cells) harbor retrotransposition events upon ectopic expression of L1, and the impact of L1 on embryonic kidney cell differentiation. Given that L1 is reactivated by aryl hydrocarbon receptor (AHR) ligands, we also sought to investigate the effects of benzo(a)pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the genetic network of mK4 cells.

Methods: The mK4 cells overexpressing human L1(RP) were assessed for changes in proliferation and expression of molecular markers of cellular differentiation.

Results: L1(RP) increased proliferation rates and markedly downregulated differentiation programming in mK4 cells. These genetic alterations were recapitulated by exogenous activation of L1 by AHR ligands.

Conclusion: L1 regulates nephrogenesis in vitro via both insertional and non-insertional mechanisms that disrupt mesenchymal to epithelial transition. Thus, a feedback loop involving L1, WT1, and AHR may play a role in regulation of kidney morphogenesis. Birth Defects Research (Part A), 2011. © 2011 Wiley-Liss, Inc.

Citing Articles

Role of long interspersed nuclear element-1 in the regulation of chromatin landscapes and genome dynamics.

Ramos K, Bojang P, Bowers E Exp Biol Med (Maywood). 2021; 246(19):2082-2097.

PMID: 34304633 PMC: 8524765. DOI: 10.1177/15353702211031247.

Comprehensive analysis based on DNA methylation and RNA-seq reveals hypermethylation of the up-regulated WT1 gene with potential mechanisms in PAM50 subtypes of breast cancer.

Ren C, Tang X, Lan H PeerJ. 2021; 9:e11377.

PMID: 33987034 PMC: 8103922. DOI: 10.7717/peerj.11377.

Epigenetic reactivation of LINE-1 retrotransposon disrupts NuRD corepressor functions and induces oncogenic transformation in human bronchial epithelial cells.

Bojang Jr P, Ramos K Mol Oncol. 2018; 12(8):1342-1357.

PMID: 29845737 PMC: 6068357. DOI: 10.1002/1878-0261.12329.

New Trends in Aryl Hydrocarbon Receptor Biology.

Mulero-Navarro S, Fernandez-Salguero P Front Cell Dev Biol. 2016; 4:45.

PMID: 27243009 PMC: 4863130. DOI: 10.3389/fcell.2016.00045.

Reprogramming of the HepG2 genome by long interspersed nuclear element-1.

Bojang Jr P, Roberts R, Anderton M, Ramos K Mol Oncol. 2013; 7(4):812-25.

PMID: 23648019 PMC: 5528423. DOI: 10.1016/j.molonc.2013.04.003.

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