The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator
The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator
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DOI：
10.1101/gad.1416106
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发表时间：
2006-06-01
影响因子：
10.5
通讯作者：
Kohtz, Jhumku D.
中科院分区：
文献类型：
--
作者：
Feng, Jianchi;Bi, Chumming;Kohtz, Jhumku D.
脊椎动物中超保守非编码序列的鉴定与发育调节因子和DNA结合蛋白有关。其中第一个是在Dlx-5和Dlx-6基因之间的基因间区域中发现的，Dlx/d11同源结构域蛋白家族的成员。在以前的实验中，我们表明，Sonic hedgehog处理前脑神经外植体导致Dlx-2和新的非编码RNA（ncRNA）Evf-1的激活。在这份报告中，我们表明，Dlx-5/6 ultraconserved区域转录产生的选择性剪接形式的Evf-1，ncRNA Evf-2。Evf-2特异性地与Dlx-2合作，以靶向和同源结构域特异性的方式增加Dlx-5/6增强子的转录活性。一个稳定的复合物含有Evf-2 ncRNA和Dlx-2蛋白在体内形成，表明Evf-2 ncRNA激活转录活性直接影响Dlx-2的活性。这些实验确定了一种新的机制，即转录控制的ncRNA和同源结构域蛋白的合作行动。脊椎动物超保守区域的一个子集可能在DNA和RNA水平发挥作用，控制关键的发育调节因子，这可能解释了为什么即使在脊椎动物进化4.5亿年后，超保守序列仍表现出90%或更多的保守性。
The identification of ultraconserved noncoding sequences in vertebrates has been associated with developmental regulators and DNA-binding proteins. One of the first of these was identified in the intergenic region between the Dlx-5 and Dlx-6 genes, members of the Dlx/d11 homeodomain-containing protein family. In previous experiments, we showed that Sonic hedgehog treatment of forebrain neural explants results in the activation of Dlx-2 and the novel noncoding RNA (ncRNA), Evf-1. In this report, we show that the Dlx-5/6 ultraconserved region is transcribed to generate an alternatively spliced form of Evf-1, the ncRNA Evf-2. Evf-2 specifically cooperates with Dlx-2 to increase the transcriptional activity of the Dlx-5/6 enhancer in a target and homeodomain-specific manner. A stable complex containing the Evf-2 ncRNA and the Dlx-2 protein forms in vivo, suggesting that the Evf-2 ncRNA activates transcriptional activity by directly influencing Dlx-2 activity. These experiments identify a novel mechanism whereby transcription is controlled by the cooperative actions of an ncRNA and a homeodomain protein. The possibility that a subset of vertebrate ultraconserved regions may function at both the DNA and RNA level to control key developmental regulators may explain why ultraconserved sequences exhibit 90% or more conservation even after 450 million years of vertebrate evolution.