Histone acetylation is involved in TCDD‑induced cleft palate formation in fetal mice

Yuan,Xingang; Qiu,Lin; Pu,Yalan; Liu,Cuiping; Zhang,Xuan; Wang,Chen; Pu,Wei; Fu,Yuexian

doi:10.3892/mmr.2016.5348

Histone acetylation is involved in TCDD‑induced cleft palate formation in fetal mice

Authors:
- Xingang Yuan
- Lin Qiu
- Yalan Pu
- Cuiping Liu
- Xuan Zhang
- Chen Wang
- Wei Pu
- Yuexian Fu
View Affiliations

Affiliations: 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, Chongqing 400014, P.R. China, Biology Teaching and Research Section of Medical Technology College, Chengdu University of Transitional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China
Published online on: May 27, 2016 https://doi.org/10.3892/mmr.2016.5348
Pages: 1139-1145
Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present was to evaluate the effects of DNA methylation and histone acetylation on 2,3,7,8‑tetrachlorodibenzo‑p‑dioxin (TCDD)‑induced cleft palate in fetal mice. Pregnant mice (n=10) were randomly divided into two groups: i) TCDD group, mice were treated with 28 µg/kg TCDD on gestation day (GD) 10 by oral gavage; ii) control group, mice were treated with an equal volume of corn oil. On GD 16.5, the fetal mice were evaluated for the presence of a cleft palate. An additional 36 pregnant mice were divided into the control and TCDD groups, and palate samples were collected on GD 13.5, GD 14.5 and GD 15.5, respectively. Transforming growth factor‑β3 (TGF‑β3) mRNA expression, TGF‑β3 promoter methylation, histone acetyltransferase (HAT) activity and histone H3 (H3) acetylation in the palates were evaluated in the two groups. The incidence of a cleft palate in the TCDD group was 93.55%, and no cases of cleft palate were identified in the control group. On GD 13.5 and GD 14.5, TGF‑β3 mRNA expression, HAT activity and acetylated H3 levels were significantly increased in the TCDD group compared with the control. Methylated bands were not observed in the TCDD or control groups. In conclusion, at the critical period of palate fusion (GD 13.5‑14.5), TCDD significantly increased TGF‑β3 gene expression, HAT activity and H3 acetylation. Therefore, histone acetylation may be involved in TCDD‑induced cleft palate formation in fetal mice.

View Figures

View References

1	Wehby GL and Cassell CH: The impact of orofacial clefts on quality of life and healthcare use and costs. Oral Dis. 16:3–10. 2010. View Article : Google Scholar
2	Leite IC, Paumgartten FJ and Koifman S: Chemical exposure during pregnancy and oral clefts in newborns. Cad Saude Publica. 18:17–31. 2002. View Article : Google Scholar : PubMed/NCBI
3	Murray JC: Gene/environment causes of cleft lip and/or palate. Clin Genet. 61:248–256. 2002. View Article : Google Scholar : PubMed/NCBI
4	Yamada T, Hirata A, Sasabe E, Yoshimura T, Ohno S, Kitamura N and Yamamoto T: TCDD disrupts posterior palato-genesis and causes cleft palate. J Craniomaxillofac Surg. 42:1–6. 2014. View Article : Google Scholar
5	Proetzel G, Pawlowski SA, Wiles MV, Yin M, Boivin GP, Howles PN, Ding J, Ferguson MW and Doetschman T: Transforming growth factor-beta 3 is required for secondary palate fusion. Nat Genet. 11:409–414. 1995. View Article : Google Scholar : PubMed/NCBI
6	Marazita ML, Lidral AC, Murray JC, Field LL, Maher BS, Goldstein McHenry T, Cooper ME, Govil M, Daack-Hirsch S, Riley B, et al: Genome scan, fine-mapping and candidate gene analysis of non-syndromic cleft lip with or without cleft palate reveals phenotype-specific differences in linkage and association results. Hum Hered. 68:151–170. 2009. View Article : Google Scholar :
7	Jenuwein T: The epigenetic magic of histone lysine methylation. FEBS J. 273:3121–3135. 2006. View Article : Google Scholar : PubMed/NCBI
8	Gan LQ, Fu YX, Liu X, Qiu L, Wu SD, Tian XF, Liu Y and Wei GH: Transforming growth factor-beta3 expression up-regulates on cleft palates induced by 2,3,7,8-tetrachloro-dibenzo-p-dioxin in mice. Toxicol Ind Health. 25:473–478. 2009. View Article : Google Scholar : PubMed/NCBI
9	Kuriyama M, Udagawa A, Yoshimoto S, Ichinose M, Sato K, Yamazaki K, Matsuno Y, Shiota K and Mori C: DNA meth-ylation changes during cleft palate formation induced by retinoic acid in mice. Cleft Palate Craniofac J. 45:545–551. 2008. View Article : Google Scholar : PubMed/NCBI
10	McClure EA, North CM, Kaminski NE and Goodman JI: Changes in DNA methylation and gene expression during 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced suppression of the lipopolysaccharide-stimulated IgM response in splenocytes. Toxicol Sci. 120:339–348. 2011. View Article : Google Scholar : PubMed/NCBI
11	Kouzarides T: Chromatin modifications and their function. Cell. 128:693–705. 2007. View Article : Google Scholar : PubMed/NCBI
12	Cuiping L, Xingang Y, Yuexian F, Lin Q, Xiaofei T, Yan L and Guanghui W: The role of histone H3 acetylation on cleft palate in mice induced by 2,3,7,8-tetrachlorodibenzopdioxin. Zhonghua Zheng Xing Wai Ke Za Zhi. 30:369–372. 2014.In Chinese. PubMed/NCBI
13	National Research Council: Guide for the Care and Use of Laboratory Animals. 8th edition. National Academy Press; Washington, DC: 2011
14	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
15	Li LC and Dahiya R: MethPrimer: Designing primers for methylation PCRs. Bioinformatics. 18:1427–1431. 2002. View Article : Google Scholar : PubMed/NCBI
16	Beaty TH, Maestri NE, Hetmanski JB, Wyszynski DF, Vanderkolk CA, Simpson JC, McIntosh I, Smith EA, Zeiger JS, Raymond GV, et al: Testing for interaction between maternal smoking and TGFA genotype among oral cleft cases born in Maryland 1992–1996. Cleft Palate Craniofac J. 34:447–454. 1997. View Article : Google Scholar : PubMed/NCBI
17	Hwang SJ, Beaty TH, Panny SR, Street NA, Joseph JM, Gordon S, McIntosh I and Francomano CA: Association study of transforming growth factor alpha (TGF alpha) TaqI polymorphism and oral clefts: Indication of gene-environment interaction in a population-based sample of infants with birth defects. Am J Epidemiol. 141:629–636. 1995.PubMed/NCBI
18	Shaw GM, Wasserman CR, Lammer EJ, O'Malley CD, Murray JC, Basart AM and Tolarova MM: Orofacial clefts, parental cigarette smoking, and transforming growth factor-alpha gene variants. Am J Hum Genet. 58:551–561. 1996.PubMed/NCBI
19	Seelan RS, Mukhopadhyay P, Pisano MM and Greene RM: Developmental epigenetics of the murine secondary palate. ILAR J. 53:240–252. 2012. View Article : Google Scholar
20	Thomae TL, Stevens EA and Bradfield CA: Transforming growth factor-beta3 restores fusion in palatal shelves exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. J Biol Chem. 280:12742–12746. 2005. View Article : Google Scholar : PubMed/NCBI
21	He X, Liu C, Pu Y, Gan L, Yuan X, Wei G and Fu Y: Be based on the morphological and histological changes to study optimal dose of TCDD induced cleft palate in mice embryo. Wei Sheng Yan Jiu. 42:277–281. 2013.In Chinese. PubMed/NCBI
22	Deaton AM, Webb S, Kerr AR, Illingworth RS, Guy J, Andrews R and Bird A: Cell type-specific DNA methylation at intragenic CpG islands in the immune system. Genome Res. 21:1074–1086. 2011. View Article : Google Scholar : PubMed/NCBI
23	Lind L, Penell J, Luttropp K, Nordfors L, Syvänen AC, Axelsson T, Salihovic S, van Bavel B, Fall T, Ingelsson E and Lind PM: Global DNA hypermethylation is associated with high serum levels of persistent organic pollutants in an elderly population. Environ Int. 59:456–461. 2013. View Article : Google Scholar : PubMed/NCBI
24	Papoutsis AJ, Borg JL, Selmin OI and Romagnolo DF: BRCA-1 promoter hypermethylation and silencing induced by the aromatic hydrocarbon receptor-ligand TCDD are prevented by resveratrol in MCF-7 cells. J Nutr Biochem. 23:1324–1332. 2012. View Article : Google Scholar
25	Manikkam M, Tracey R, Guerrero-Bosagna C and Skinner MK: Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations. PLoS One. 7:e462492012. View Article : Google Scholar : PubMed/NCBI
26	Ornoy A: Valproic acid in pregnancy: How much are we endangering the embryo and fetus? Reprod Toxicol. 28:1–10. 2009. View Article : Google Scholar : PubMed/NCBI
27	Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA and Klein PS: Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer and teratogen. J Biol Chem. 276:36734–36741. 2001. View Article : Google Scholar : PubMed/NCBI
28	Takeda T, Fujii M, Taura J, Ishii Y and Yamada H: Dioxin silences gonadotropin expression in perinatal pups by inducing histone deacetylases: A new insight into the mechanism for the imprinting of sexual immaturity by dioxin. J Biol Chem. 287:18440–18450. 2012. View Article : Google Scholar : PubMed/NCBI
29	Ingelman-Sundberg M, Zhong XB, Hankinson O, Beedanagari S, Yu AM, Peng L and Osawa Y: Potential role of epigenetic mechanisms in the regulation of drug metabolism and transport. Drug Metab Dispos. 41:1725–1731. 2013. View Article : Google Scholar : PubMed/NCBI