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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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2017-02-01
Series:Stem Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S221367111630306X
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spelling 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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