Inhibition of Gata4 and Tbx5 by Nicotine-Mediated DNA Methylation in Myocardial Differentiation.
Inhibition of Gata4 and Tbx5 by Nicotine-Mediated DNA Methylation in Myocardial Differentiation.
复制标题
尼古丁介导的 DNA 甲基化对心肌分化中 Gata4 和 Tbx5 的抑制
DOI：
10.1016/j.stemcr.2016.12.016
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发表时间：
2017-02-14
影响因子：
5.9
通讯作者：
Yu XY
中科院分区：
文献类型：
--
作者：
Jiang XY;Feng YL;Ye LT;Li XH;Feng J;Zhang MZ;Shelat HS;Wassler M;Li Y;Geng YJ;Yu XY
母体尼古丁暴露导致基因表达和心血管编程的改变。尼古丁对心脏发生的调节作用的发现对于心脏缺陷的研究具有重要意义。本研究探讨尼古丁对心肌分化过程中心脏基因表达和表观遗传调控的影响。持续尼古丁暴露通过启动子DNA超甲基化选择性抑制两个心脏基因Tbx5和Gata4的表达。烟碱诱导的抑制心肌分化恢复一般烟碱乙酰胆碱受体抑制。从后代的体内研究中获得了Tbx5和Gata4基因抑制和心功能损害伴左心室射血分数降低的一致结果。我们的研究结果表明，尼古丁对心肌分化的直接抑制作用，通过调节心脏基因抑制通过启动子DNA超甲基化，有助于吸烟相关的心脏缺陷的病因。尼古丁在体外和体内心脏发生过程中下调Tbx5和Gata4尼古丁导致心脏分化减少和心脏功能受损尼古丁通过启动子DNA超甲基化导致Tbx5和Gata4基因抑制nAChR拮抗剂恢复尼古丁诱导的基因抑制和DNA甲基化在这篇文章中，Yu，Geng，和同事揭示了尼古丁通过调节抑制两个心脏基因对心肌分化的直接抑制作用（Gata 4和Tbx 5）通过启动子DNA超甲基化，导致吸烟相关心脏缺陷的病因。
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. Nicotine downregulates Tbx5 and Gata4 during in vitro and in vivo cardiogenesis Nicotine causes diminished cardiac differentiation and impaired cardiac function Nicotine causes Tbx5 and Gata4 gene suppression via promoter DNA hypermethylation nAChR antagonist restores nicotine-induced gene suppression and DNA methylation In this article, Yu, Geng, and colleagues reveal a direct repressive effect of nicotine on myocardial differentiation by regulating suppression of two cardiac genes (Gata4 and Tbx5) via promoter DNA hypermethylation, contributing to the etiology of smoking-associated cardiac defects.