Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Aug;14(2):1139-45.
doi: 10.3892/mmr.2016.5348. Epub 2016 May 27.

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

Xingang Yuan  1 , Lin Qiu  1 , Yalan Pu  1 , Cuiping Liu  1 , Xuan Zhang  1 , Chen Wang  1 , Wei Pu  2 , Yuexian Fu  1
Affiliations

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

Xingang Yuan et al. Mol Med Rep. 2016 Aug.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Transforming growth factor-β3 CpG island locations.
Figure 2
Figure 2
Histology of the palate on GD 16.5. (A) Control group and (B) TCDD group. Stained with hematoxylin and eosin. Magnification, ×40. GD, gestation day; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Figure 3
Figure 3
TGF-β3 mRNA expression on GD 13.5, GD 14.5 and GD 15.5 in the TCDD and control groups. Data are presented as the mean ± standard deviation. *P<0.01 and #P<0.05 vs. the control group. TGF-β3, transforming growth factor-β3; GD, gestation day; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Figure 4
Figure 4
Detection of methylation status in the TGF-β3 gene promoter by methylation-specific polymerase chain reaction. Marker, 100–600 bp; M, methylation band (138 bp); U, nonmethylated band (141 bp); 1–3, GD13.5, GD14.5, and GD15.5, respectively, in the control group; 4–6, GD13.5, GD14.5 and GD15.5, respectively, in the TCDD group. TGF-β3, transforming growth factor-β3; GD, gestation day; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Figure 5
Figure 5
HAT activity in the cleft palate on GD 13.5, GD 14.5 and GD v15.5 in the control and TCDD groups. Data are presented as the mean ± standard deviation. *P<0.01 vs. the control group. HAT, histone acetyltransferase; GD, gestation day; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Figure 6
Figure 6
Detection of Ac-H3 in the TCDD and control groups by western blotting. (A) Representative blot. (B) Statistical analysis of the acetylated histone H3 level. Data are presented as the mean ± standard deviation. *P<0.01 and #P<0.05 vs. the control group. N, control group, T, TCDD group. Ac-H3, acetylated histone 3; GD, gestation day; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Wehby GL, Cassell CH. The impact of orofacial clefts on quality of life and healthcare use and costs. Oral Dis. 2010;16:3–10. doi: 10.1111/j.1601-0825.2009.01588.x. - DOI - PMC - PubMed
    1. Leite IC, Paumgartten FJ, Koifman S. Chemical exposure during pregnancy and oral clefts in newborns. Cad Saude Publica. 2002;18:17–31. doi: 10.1590/S0102-311X2002000100003. - DOI - PubMed
    1. Murray JC. Gene/environment causes of cleft lip and/or palate. Clin Genet. 2002;61:248–256. doi: 10.1034/j.1399-0004.2002.610402.x. - DOI - PubMed
    1. Yamada T, Hirata A, Sasabe E, Yoshimura T, Ohno S, Kitamura N, Yamamoto T. TCDD disrupts posterior palato-genesis and causes cleft palate. J Craniomaxillofac Surg. 2014;42:1–6. doi: 10.1016/j.jcms.2013.01.024. - DOI - PubMed
    1. Proetzel G, Pawlowski SA, Wiles MV, Yin M, Boivin GP, Howles PN, Ding J, Ferguson MW, Doetschman T. Transforming growth factor-beta 3 is required for secondary palate fusion. Nat Genet. 1995;11:409–414. doi: 10.1038/ng1295-409. - DOI - PMC - PubMed

MeSH terms