A noncoding RNA regulates the neurogenin1 gene locus during mouse neocortical development
A noncoding RNA regulates the neurogenin1 gene locus during mouse neocortical development
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DOI：
10.1073/pnas.1202956109
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发表时间：
2012-10-16
影响因子：
11.1
通讯作者：
Gotoh, Yukiko
中科院分区：
文献类型：
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作者：
Onoguchi, Masahiro;Hirabayashi, Yusuke;Gotoh, Yukiko
前神经碱性螺旋-环-螺旋（bHLH）转录因子神经生成素1（Neurog 1）在哺乳动物发育过程中的神经元分化中起着关键作用。Neurog 1基因表达的时空控制是由几个特定的增强子元件介导的，尽管这些元件如何调节Neurog 1基因座仍然很不清楚。最近，它已被证明，大量的增强子元件被转录，但所产生的转录本的调节和功能已被调查，只有几个这样的元素。我们现在表明，位于5.8-7.0 kb的小鼠Neurog 1基因座上游的增强子元件被转录。这种转录物的产生，命名为utNgn 1，与神经元分化过程中的Neurog 1 mRNA高度相关。此外，通过相应的短干扰RNA敲低utNgn 1抑制响应于神经元分化诱导的Neurog 1 mRNA的产生。我们还发现，utNgn 1的产生受到polycomb组（PcG）蛋白的抑制，该蛋白抑制Neurog 1的表达。因此，我们的研究结果表明，从增强子元件转录的非编码RNA正调控Neurog 1基因座的转录。
The proneural basic helix-loop-helix (bHLH) transcription factor neurogenin1 (Neurog1) plays a pivotal role in neuronal differentiation during mammalian development. The spatiotemporal control of the Neurog1 gene expression is mediated by several specific enhancer elements, although how these elements regulate the Neurog1 locus has remained largely unclear. Recently it has been shown that a large number of enhancer elements are transcribed, but the regulation and function of the resulting transcripts have been investigated for only several such elements. We now show that an enhancer element located 5.8-7.0 kb upstream of the mouse Neurog1 locus is transcribed. The production of this transcript, designated utNgn1, is highly correlated with that of Neurog1 mRNA during neuronal differentiation. Moreover, knockdown of utNgn1 by a corresponding short interfering RNA inhibits the production of Neurog1 mRNA in response to induction of neuronal differentiation. We also found that production of utNgn1 is suppressed by polycomb group (PcG) proteins, which inhibit the expression of Neurog1. Our results thus suggest that a noncoding RNA transcribed from an enhancer element positively regulates transcription at the Neurog1 locus.