Inhibition of Gata4 and Tbx5 by Nicotine-Mediated DNA Methylation in Myocardial Differentiation
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 an...
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doaj-47663bfbb8d945daa6667a118cf373512020-11-24T22:49:50ZengElsevierStem Cell Reports2213-67112017-02-018229030410.1016/j.stemcr.2016.12.016Inhibition of Gata4 and Tbx5 by Nicotine-Mediated DNA Methylation in Myocardial DifferentiationXue-Yan Jiang0Yu-Liang Feng1Li-Tong Ye2Xiao-Hong Li3Juan Feng4Meng-Zhen Zhang5Harnath S. Shelat6Michael Wassler7Yangxin Li8Yong-Jian Geng9Xi-Yong Yu10Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, P.R. ChinaGuangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, P.R. ChinaGuangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, P.R. ChinaGuangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, P.R. ChinaGuangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, P.R. ChinaGuangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, P.R. ChinaThe Center for Cardiovascular Biology and Atherosclerosis Research, University of Texas McGovern School of Medicine, and Texas Heart Institute, Houston, TX 77030, USAThe Center for Cardiovascular Biology and Atherosclerosis Research, University of Texas McGovern School of Medicine, and Texas Heart Institute, Houston, TX 77030, USAThe Center for Cardiovascular Biology and Atherosclerosis Research, University of Texas McGovern School of Medicine, and Texas Heart Institute, Houston, TX 77030, USAThe Center for Cardiovascular Biology and Atherosclerosis Research, University of Texas McGovern School of Medicine, and Texas Heart Institute, Houston, TX 77030, USAGuangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, P.R. ChinaMaternal 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.http://www.sciencedirect.com/science/article/pii/S221367111630306X |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xue-Yan Jiang Yu-Liang Feng Li-Tong Ye Xiao-Hong Li Juan Feng Meng-Zhen Zhang Harnath S. Shelat Michael Wassler Yangxin Li Yong-Jian Geng Xi-Yong Yu |
spellingShingle |
Xue-Yan Jiang Yu-Liang Feng Li-Tong Ye Xiao-Hong Li Juan Feng Meng-Zhen Zhang Harnath S. Shelat Michael Wassler Yangxin Li Yong-Jian Geng Xi-Yong Yu Inhibition of Gata4 and Tbx5 by Nicotine-Mediated DNA Methylation in Myocardial Differentiation Stem Cell Reports |
author_facet |
Xue-Yan Jiang Yu-Liang Feng Li-Tong Ye Xiao-Hong Li Juan Feng Meng-Zhen Zhang Harnath S. Shelat Michael Wassler Yangxin Li Yong-Jian Geng Xi-Yong Yu |
author_sort |
Xue-Yan Jiang |
title |
Inhibition of Gata4 and Tbx5 by Nicotine-Mediated DNA Methylation in Myocardial Differentiation |
title_short |
Inhibition of Gata4 and Tbx5 by Nicotine-Mediated DNA Methylation in Myocardial Differentiation |
title_full |
Inhibition of Gata4 and Tbx5 by Nicotine-Mediated DNA Methylation in Myocardial Differentiation |
title_fullStr |
Inhibition of Gata4 and Tbx5 by Nicotine-Mediated DNA Methylation in Myocardial Differentiation |
title_full_unstemmed |
Inhibition of Gata4 and Tbx5 by Nicotine-Mediated DNA Methylation in Myocardial Differentiation |
title_sort |
inhibition of gata4 and tbx5 by nicotine-mediated dna methylation in myocardial differentiation |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2017-02-01 |
description |
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. |
url |
http://www.sciencedirect.com/science/article/pii/S221367111630306X |
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