title: Prenatal alcohol exposure causes the over-expression of DHAND and EHAND by increasing histone H3K14 acetylation in C57 BL/6 mice.
abstract: Prenatal alcohol exposure leads to congenital heart abnormal development, its mechanisms are still unknown. Recent reports have associated alcohol exposure with histone H3 acetylation. In the present study, we have performed the experiments to test the hypothesis that histone H3K14 acetylation is the key role in the fetal heart leads to over-expression of cardiac specific genes DHAND and EHAND caused by prenatal alcohol exposure. Seventy pregnant C57BL/6 mice were divided randomly into seven groups (n=10). They were the untreated group, dimethyl sulfoxide group, alcohol exposure group, curcumin treatment group, both alcohol and curcumin treatment group, SAHA treatment group, both alcohol and SAHA treatment group. Fetal mouse hearts were collected on embryonic day 14.5. The changes of HATs activities, the acetylation levels of histone H3K14 (H3K14ac), the expression levels of cardiac specific genes DHAND and EHAND, and structure of chromatin were determined. Our data indicates that curcumin and SAHA significantly reduces and increases the activities of HATs and the levels of histone H3K14ac in fetal hearts, respectively. The expression of DHAND and EHAND is significantly down-regulated and up-regulated in the groups treated with curcumin and SAHA. Furthermore, our results from ChIP assays have shown that the histone H3K14ac connects with the DHAND and EHAND genes are significantly inhibited by curcumin and simulated by SAHA. Our study suggests that prenatal alcohol exposure causes the over-expression of DHAND and EHAND by increasing H3K14ac in mice.
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China.
authors.forename: Chang
authors.initials: C
authors.lastname: Peng
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China.
authors.forename: Wenqun
authors.initials: W
authors.lastname: Gao
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, PR China; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China.
authors.forename: Tiewei
authors.initials: T
authors.lastname: Lv
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, PR China; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, PR China.
authors.forename: Lingjuan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Ohio State University Medical Center, Richard Ross Heart Hospital Cardiology, Columbus, OH, USA.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China.
authors.forename: Huan
authors.initials: H
authors.lastname: Li
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xv
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, PR China. Electronic address: jietian@cqmu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
mesh_terms: D000107:Acetylation; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D000431:Ethanol; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D005318:Fetal Heart / Q000187:drug effects / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D015854:Up-Regulation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000431:Ethanol; D056572:Histone Deacetylase Inhibitors; D006657:Histones; C095572:Hand1 protein, mouse; C498766:Hand2 protein, mouse; C097341:helix-loop-helix protein, eHAND
keywords: Curcumin; DHAND; EHAND; Histone H3K14 acetylation; Prenatal alcohol exposure; SAHA