Epigenetics and the control of epithelial sodium channel expression in collecting duct.
Epigenetics and the control of epithelial sodium channel expression in collecting duct.
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集合管上皮钠通道表达的表观遗传学和控制。
DOI：
10.1038/ki.2008.475
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发表时间：
2009-02
影响因子：
19.6
通讯作者：
Kone, Bruce C.
中科院分区：
文献类型：
--
作者：
Zhang, Dongyu;Yu, Zhi-yuan;Cruz, Pedro;Kong, Qun;Li, Shiyu;Kone, Bruce C.
在真核生物细胞核中，基因组DNA与组蛋白和非组蛋白紧密结合，形成一种称为染色质的动态聚合物。通过组蛋白修饰、染色质因子的作用或DNA甲基化来重组染色质结构，可以深刻地改变基因表达。这些表观遗传修饰允许在不改变DNA序列的情况下发生遗传和潜在可逆的基因功能变化，从而扩展了遗传密码的信息潜力。本文介绍了肾脏研究人员的表观遗传学概念，并概述了我们的工作，详细介绍了醛固酮信号传导的表观遗传学途径和收集管中上皮Na+通道-α亚基（ENaCα）基因表达的控制。这一新的通路涉及一个核抑制因子复合物，包括组蛋白H3 Lys-79甲基转移酶Dot1a、Af9（一种序列特异性dna结合蛋白，可结合ENaCα启动子）和其他潜在的核蛋白。该复合物调节与ENaCα启动子相关的染色质的靶向组蛋白H3 Lys-79甲基化，从而抑制其转录活性。醛固酮通过Sgk1磷酸化Af9破坏Dot1a-Af9的相互作用，抑制Dot1a和Af9的表达，导致组蛋白H3 Lys-79在特定亚区低甲基化，去抑制ENaCα启动子。Dot1a-Af9通路也可能参与控制与肾纤维化和高血压有关的基因。
In eukaryotic nuclei, genomic DNA is compacted with histone and non-histone proteins into a dynamic polymer termed chromatin. Reorganization of chromatin structure through histone modifications, the action of chromatin factors, or DNA methylation, can profoundly change gene expression. These epigenetic modifications allow heritable and potentially reversible changes in gene functioning to occur without altering the DNA sequence, thus extending the information potential of the genetic code. This review provides an introduction to epigenetic concepts for renal investigators and an overview of our work detailing an epigenetic pathway for aldosterone-signaling and the control of epithelial Na+ channel-α subunit (ENaCα) gene expression in the collecting duct. This new pathway involves a nuclear repressor complex, consisting of histone H3 Lys-79 methyltransferase Dot1a, Af9, a sequence-specific DNA-binding protein that binds the ENaCα promoter, and potentially other nuclear proteins. This complex regulates targeted histone H3 Lys-79 methylation of chromatin associated with the ENaCα promoter, thereby suppressing its transcriptional activity. Aldosterone disrupts the Dot1a-Af9 interaction via Sgk1 phosphorylation of Af9, and inhibits Dot1a and Af9 expression, resulting in histone H3 Lys-79 hypomethylation at specific subregions, and de-repression of the ENaCα promoter. The Dot1a-Af9 pathway may also be involved in the control of genes implicated in renal fibrosis and hypertension.
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影响因子：
64.5
作者：
Garcia-Bassets, Ivan;Kwon, Young-Soo;Rosenfeld, Michael G.
通讯作者：
Rosenfeld, Michael G.
影响因子：
3.6
作者：
Kikuchi, Ryota;Kusuhara, Hiroyuki;Sugiyama, Yuichi
通讯作者：
Sugiyama, Yuichi
影响因子：
11.2
作者：
Kort, Eric J.;Farber, Leslie;Teh, Bin T.
通讯作者：
Teh, Bin T.
影响因子：
9.2
作者：
Feng, Q;Wang, HB;Zhang, Y
通讯作者：
Zhang, Y
DOI：
10.1073/pnas.0611192104
发表时间：
2007-02-27
影响因子：
11.1
作者：
Kato, Mitsuo;Zhang, Jane;Natarajan, Rama
通讯作者：
Natarajan, Rama