Epigenetic control of embryonic renal cell differentiation by L1 retrotransposon

Kenneth S. Ramos, Diego E. Montoya-Durango, Ivo Teneng, Adrian Nanez, Vilius Stribinskis

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)693-702
Number of pages10
JournalBirth Defects Research Part A - Clinical and Molecular Teratology
Volume91
Issue number8
DOIs
StatePublished - Aug 2011

Keywords

  • 5' untranslated region
  • Benzo(a)pyrene (BaP)
  • Histone acetylation
  • Histone methylation
  • Long interspersed nuclear element-1 (LINE-1 or L1)
  • Nephrogenesis
  • Polycyclic aromatic hydrocarbons (PAHs)
  • Wilms' Tumor suppressor (WT1)

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Embryology
  • Developmental Biology

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