Epigenetic control of embryonic renal cell differentiation by L1 retrotransposon.
Birth Defects Res A Clin Mol Teratol
; 91(8): 693-702, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21384534
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Retroelementos
/
Regulação da Expressão Gênica no Desenvolvimento
/
Epigênese Genética
/
Rim
Limite:
Animals
Idioma:
En
Revista:
Birth Defects Res A Clin Mol Teratol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos