title: Inhibition of histone H3K9 acetylation by anacardic acid can correct the over-expression of Gata4 in the hearts of fetal mice exposed to alcohol during pregnancy.
abstract: BACKGROUND
  Cardiovascular malformations can be caused by abnormalities in Gata4 expression during fetal development. In a previous study, we demonstrated that ethanol exposure could lead to histone hyperacetylation and Gata4 over-expression in fetal mouse hearts. However, the potential mechanisms of histone hyperacetylation and Gata4 over-expression induced by ethanol remain unclear.
  
  
  RESULTS
  Pregnant mice were gavaged with ethanol or saline. Fetal mouse hearts were collected for analysis. The results of ethanol fed groups showed that global HAT activity was unusually high in the hearts of fetal mice while global HDAC activity remained unchanged. Binding of P300, CBP, PCAF, SRC1, but not GCN5, were increased on the Gata4 promoter relative to the saline treated group. Increased acetylation of H3K9 and increased mRNA expression of Gata4, α-MHC, cTnT were observed in these hearts. Treatment with the pan-histone acetylase inhibitor, anacardic acid, reduced the binding of P300, PCAF to the Gata4 promoter and reversed H3K9 hyperacetylation in the presence of ethanol. Interestingly, anacardic acid attenuated over-expression of Gata4, α-MHC and cTnT in fetal mouse hearts exposed to ethanol.
  
  
  CONCLUSIONS
  Our results suggest that P300 and PCAF may be critical regulatory factors that mediate Gata4 over-expression induced by ethanol exposure. Alternatively, P300, PCAF and Gata4 may coordinate over-expression of cardiac downstream genes in mouse hearts exposed to ethanol. Anacardic acid may thus protect against ethanol-induced Gata4, α-MHC, cTnT over-expression by inhibiting the binding of P300 and PCAF to the promoter region of these genes.
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Peng
authors.affiliation: Key Laboratory of Pediatrics in Chongqing, Chongqing, China; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Hui-Chao
authors.initials: HC
authors.lastname: Sun
authors.affiliation: Department of Biomedical Science, Charlie E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida, United States of America.
authors.forename: Xu-Pei
authors.initials: XP
authors.lastname: Huang
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Wei-An
authors.initials: WA
authors.lastname: Zhao
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, China; Key Laboratory of Pediatrics in Chongqing, Chongqing, China.
authors.forename: Ling-Juan
authors.initials: LJ
authors.lastname: Liu
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
mesh_terms: D000107:Acetylation / Q000187:drug effects; D048729:Anacardic Acids / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D050991:GATA4 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D006657:Histones / Q000378:metabolism*; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D048729:Anacardic Acids; D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D006657:Histones; C088115:anacardic acid; D000431:Ethanol
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