Determinants of orofacial clefting II: Effects of 5-Aza-2'-deoxycytidine on gene methylation during development of the first branchial arch.
Reprod Toxicol
; 67: 100-110, 2017 01.
Article
em En
| MEDLINE
| ID: mdl-27923600
ABSTRACT
Defects in development of the secondary palate, which arise from the embryonic first branchial arch (1-BA), can cause cleft palate (CP). Administration of 5-Aza-2'-deoxycytidine (AzaD), a demethylating agent, to pregnant mice on gestational day 9.5 resulted in complete penetrance of CP in fetuses. Several genes critical for normal palatogenesis were found to be upregulated in 1-BA, 12h after AzaD exposure. MethylCap-Seq (MCS) analysis identified several differentially methylated regions (DMRs) in DNA extracted from AzaD-exposed 1-BAs. Hypomethylated DMRs did not correlate with the upregulation of genes in AzaD-exposed 1-BAs. However, most DMRs were associated with endogenous retroviral elements. Expression analyses suggested that interferon signaling was activated in AzaD-exposed 1-BAs. Our data, thus, suggest that a 12-h in utero AzaD exposure demethylates and activates endogenous retroviral elements in the 1-BA, thereby triggering an interferon-mediated response. This may result in the dysregulation of key signaling pathways during palatogenesis, causing CP.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Azacitidina
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Região Branquial
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Fissura Palatina
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Regulação da Expressão Gênica no Desenvolvimento
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Metilação de DNA
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Desenvolvimento Embrionário
Limite:
Animals
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Pregnancy
Idioma:
En
Revista:
Reprod Toxicol
Assunto da revista:
EMBRIOLOGIA
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MEDICINA REPRODUTIVA
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TOXICOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article