Preliminary research on DNA methylation changes during murine palatogenesis induced by TCDD.
2,3,7,8-Tetrachlrodibenzo-p-dioxin (TCDD) has been shown to induce cleft palate through growth factor and receptor expression changes during palatogenesis. DNA methylation is an important epigenetic modification that can regulate gene expressions and may be involved in TCDD-induced cleft palate. In this study, we investigated the effects of TCDD on the global and CpG DNA methylation status and the expression levels of DNA methyltransferases (Dnmts) in palate tissue of fetal mice. Pregnant C57BL/6J mice were administered with corn oil or TCDD 28 μg/kg at gestation day 10.5(GD10.5), and sacrificed at GD13.5, 14.5, 15.5. Fetal palates were collected for molecular analysis. Global DNA methylation status was detected by Methylamp™ Global DNA Methylation Quantification Ultra Kit. The expression of DNA methyltransferases were examined by quantitative real-time PCR(q-PCR). Methylation Specific PCR (MSP) was performed to analyze CpG methylation status of Dnmts. We found that the global DNA methylation level and the expression of Dnmt3a were higher at GD13.5 in the TCDD group. The methylation level of CpG site 2 in the promoter region of Dnmt3a in the control group was higher than that of the TCDD group at GD13.5. The low CpG methylation level of Dnmt3a at GD13.5 which causes the up-expression of Dnmt3a may induce global hypermethylation in fetal palate tissue. The aberrant global methylation status at GD13.5 may be the cause of palate malformation in fetal mice induced by TCDD.
Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Department of Burns and Plastic Surgery, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
Chen
C
Wang
Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Department of Burns and Plastic Surgery, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
Xin-Gang
XG
Yuan
Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Department of Burns and Plastic Surgery, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
Cui-Ping
CP
Liu
Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Department of Burns and Plastic Surgery, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
Sha-Na
SN
Zhai
Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Department of Burns and Plastic Surgery, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
Ding-Wen
DW
Zhang
Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Department of Burns and Plastic Surgery, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. Electronic address: yuexianfu@163.com.
Yue-Xian
YX
Fu
D000818:Animals; D002972:Cleft Palate / Q000139:chemically induced*; D019175:DNA Methylation / Q000187:drug effects*; D015254:DNA Modification Methylases / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010159:Palate / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction
D000072317:Polychlorinated Dibenzodioxins; D015254:DNA Modification Methylases
2,3,7,8-Tetrachlrodibenzo-p-dioxin; Cleft palate; CpG island; DNA methylation; DNA methyltransferases (Dnmts)