title: Inhibition of Gata4 and Tbx5 by Nicotine-Mediated DNA Methylation in Myocardial Differentiation.
abstract: Maternal nicotine exposure causes alteration of gene expression and cardiovascular programming. The discovery of nicotine-medicated regulation in cardiogenesis is of major importance for the study of cardiac defects. The present study investigated the effect of nicotine on cardiac gene expression and epigenetic regulation during myocardial differentiation. Persistent nicotine exposure selectively inhibited expression of two cardiac genes, Tbx5 and Gata4, by promoter DNA hypermethylation. The nicotine-induced suppression on cardiac differentiation was restored by general nicotinic acetylcholine receptor inhibition. Consistent results of Tbx5 and Gata4 gene suppression and cardiac function impairment with decreased left ventricular ejection fraction were obtained from in vivo studies in offspring. Our results present a direct repressive effect of nicotine on myocardial differentiation by regulating cardiac gene suppression via promoter DNA hypermethylation, contributing to the etiology of smoking-associated cardiac defects.
authors.affiliation: Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, P.R. China; The Center for Cardiovascular Biology and Atherosclerosis Research, University of Texas McGovern School of Medicine, and Texas Heart Institute, Houston, TX 77030, USA.
authors.forename: Xue-Yan
authors.initials: XY
authors.lastname: Jiang
authors.affiliation: Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, P.R. China; Key Laboratory of Molecular Clinical Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, P.R. China.
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Feng
authors.affiliation: Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, P.R. China.
authors.forename: Li-Tong
authors.initials: LT
authors.lastname: Ye
authors.affiliation: Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, P.R. China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Li
authors.affiliation: Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Feng
authors.affiliation: Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, P.R. China.
authors.forename: Meng-Zhen
authors.initials: MZ
authors.lastname: Zhang
authors.affiliation: The Center for Cardiovascular Biology and Atherosclerosis Research, University of Texas McGovern School of Medicine, and Texas Heart Institute, Houston, TX 77030, USA.
authors.forename: Harnath S
authors.initials: HS
authors.lastname: Shelat
authors.affiliation: The Center for Cardiovascular Biology and Atherosclerosis Research, University of Texas McGovern School of Medicine, and Texas Heart Institute, Houston, TX 77030, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wassler
authors.affiliation: The Center for Cardiovascular Biology and Atherosclerosis Research, University of Texas McGovern School of Medicine, and Texas Heart Institute, Houston, TX 77030, USA.
authors.forename: Yangxin
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Center for Cardiovascular Biology and Atherosclerosis Research, University of Texas McGovern School of Medicine, and Texas Heart Institute, Houston, TX 77030, USA. Electronic address: yong-jian.geng@uth.tmc.edu.
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Geng
authors.affiliation: Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, P.R. China; Key Laboratory of Molecular Clinical Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, P.R. China. Electronic address: yuxycn@aliyun.com.
authors.forename: Xi-Yong
authors.initials: XY
authors.lastname: Yu
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D000076123:DNA (Cytosine-5-)-Methyltransferase 1 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D058732:Embryoid Bodies; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D032342:Muscle Cells / Q000166:cytology* / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics*
chemical_list: D050991:GATA4 Transcription Factor; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; D009538:Nicotine; D000076123:DNA (Cytosine-5-)-Methyltransferase 1