Sex-dependent gene regulatory networks of the heart rhythm
Sex-dependent gene regulatory networks of the heart rhythm
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DOI：
10.1007/s10142-009-0137-8
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发表时间：
2010-03-01
影响因子：
2.9
通讯作者：
Spray, D. C.
中科院分区：
文献类型：
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作者：
Iacobas, D. A.;Iacobas, S.;Spray, D. C.
比较了66个选定的心律决定基因（HRD）在4只雄性和4只雌性成年小鼠心房和心室中的表达水平、控制和相互协调。我们发现，编码各种肾上腺素能受体、锚定蛋白、离子通道和转运蛋白、连接蛋白、钙粘蛋白、嗜血小板蛋白和嵌入盘的其他成分的基因形成了一个复杂的网络，这个网络依赖于腔室，在两性之间是不同的。此外，大多数HRD基因在心房中的表达水平在男性中高于女性，而在心室中，女性的表达水平大多高于男性。此外，在两性之间观察到显著的腔室差异，男性心房的表达高于心室，女性心室的表达高于心房。我们根据它们在HRD基因网中的突出性（新概念）对所选基因进行了排序，HRD基因网的定义是与其他网络基因的表达协调程度和表达稳定性。有趣的是，两性之间的突出等级有很大的不同。综上所述，这些发现表明心律转录组的组织原则是性别依赖的，新引入的突出分析允许识别对性别二分法至关重要的基因。
Expression level, control, and intercoordination of 66 selected heart rhythm determinant (HRD) genes were compared in atria and ventricles of four male and four female adult mice. We found that genes encoding various adrenergic receptors, ankyrins, ion channels and transporters, connexins, cadherins, plakophilins, and other components of the intercalated discs form a complex network that is chamber dependent and differs between the two sexes. In addition, most HRD genes in atria had higher expression in males than in females, while in ventricles, expression levels were mostly higher in females than in males. Moreover, significant chamber differences were observed between the sexes, with higher expression in atria than ventricles for males and higher expression in ventricles than atria for females. We have ranked the selected genes according to their prominence (new concept) within the HRD gene web defined as extent of expression coordination with the other web genes and stability of expression. Interestingly, the prominence hierarchy was substantially different between the two sexes. Taken together, these findings indicate that the organizational principles of the heart rhythm transcriptome are sex dependent, with the newly introduced prominence analysis allowing identification of genes that are pivotal for the sexual dichotomy.