Cx30.2 enhancer analysis identifies Gata4 as a novel regulator of atrioventricular delay
Cx30.2 enhancer analysis identifies Gata4 as a novel regulator of atrioventricular delay
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DOI：
10.1242/dev.038562
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发表时间：
2009-08-01
期刊：
影响因子：
4.6
通讯作者：
Olson, Eric N.
中科院分区：
文献类型：
--
作者：
Munshi, Nikhil V.;McAnally, John;Olson, Eric N.
心脏传导系统由一组特殊的电耦合心肌细胞组成，负责通过心脏传播脉冲。心脏传导异常导致多种形式的心律失常，但对控制传导系统形成的基因调控机制知之甚少。我们证明了连接蛋白30.2(Cx30.2，也称为Gjd3)基因的末端增强子是直接表达发育中的房室传导系统(AvCs)的必要条件和充分条件，该基因编码了小鼠正常房室延迟所需的缝隙连接蛋白。此外，我们发现这种增强子需要Tbx5和Gata4才能在传导系统中正确表达，而Gata4(+/-)小鼠有较短的PR间期，表明房室传导加速。因此，我们的结果表明Gata4参与了传导系统的功能，并为影响正常房室延迟的转录途径提供了更清晰的理解。
The cardiac conduction system comprises a specialized tract of electrically coupled cardiomyocytes responsible for impulse propagation through the heart. Abnormalities in cardiac conduction are responsible for numerous forms of cardiac arrhythmias, but relatively little is known about the gene regulatory mechanisms that control the formation of the conduction system. We demonstrate that a distal enhancer for the connexin 30.2 (Cx30.2, also known as Gjd3) gene, which encodes a gap junction protein required for normal atrioventricular (AV) delay in mice, is necessary and sufficient to direct expression to the developing AV conduction system (AVCS). Moreover, we show that this enhancer requires Tbx5 and Gata4 for proper expression in the conduction system, and Gata4(+/-) mice have short PR intervals indicative of accelerated AV conduction. Thus, our results implicate Gata4 in conduction system function and provide a clearer understanding of the transcriptional pathways that impact normal AV delay.