Regulation of tyrosine hydroxylase transcription by hnRNP K and DNA secondary structure.
Regulation of tyrosine hydroxylase transcription by hnRNP K and DNA secondary structure.
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DOI：
10.1038/ncomms6769
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发表时间：
2014-12-10
影响因子：
16.6
通讯作者：
Cave, John W.
中科院分区：
文献类型：
--
作者：
Banerjee, Kasturi;Wang, Meng;Cai, Elizabeth;Fujiwara, Nana;Baker, Harriet;Cave, John W.
酪氨酸羟化酶基因（Th）转录的调节是确定和维持多巴胺能神经元表型的关键。在这里，我们定义了一个分子调节机制Th转录保守的四足脊椎动物。我们发现，异质核核糖核蛋白（hnRNP）K是Th转录的反式激活因子。它结合到以前未报道的和进化上保守的G：C-丰富的Th近端启动子的区域。hnRNP K直接结合这些保守区域内的富含C的单链DNA，并且当蛋白质（例如CREB）结合到相邻的顺式调节元件时也与双链序列相关联。在保守的富含G：C的区域内的单链DNA采用G-四链体或i-基序二级结构。我们还表明，这些二级结构的小分子介导的稳定抑制Th启动子活性。这些数据表明，这些二级结构的多巴胺能表型的药理学调制的目标。
Regulation of tyrosine hydroxylase gene (Th) transcription is critical for specifying and maintaining the dopaminergic neuronal phenotype. Here we define a molecular regulatory mechanism for Th transcription conserved in tetrapod vertebrates. We show that heterogeneous nuclear ribonucleoprotein (hnRNP) K is a transactivator of Th transcription. It binds to previously unreported and evolutionarily conserved G:C-rich regions in the Th proximal promoter. hnRNP K directly binds C-rich single DNA strands within these conserved regions and also associates with double-stranded sequences when proteins, such as CREB, are bound to an adjacent cis-regulatory element. The single DNA strands within the conserved G:C-rich regions adopt either G-quadruplex or i-motif secondary structures. We also show that small molecule-mediated stabilization of these secondary structures represses Th promoter activity. These data suggest that these secondary structures are targets for pharmacological modulation of the dopaminergic phenotype.
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影响因子：
2.9
作者：
Fedoroff, OY;Rangan, A;Hurley, LH
通讯作者：
Hurley, LH
影响因子：
15
作者：
Han, HY;Langley, DR;Hurley, LH
通讯作者：
Hurley, LH
DOI：
10.1006/bbrc.2000.3204
发表时间：
2000-08-11
影响因子：
3.1
作者：
Iwawaki, T;Kohno, K;Kobayashi, K
通讯作者：
Kobayashi, K
影响因子：
15
作者：
Han, FXG;Wheelhouse, RT;Hurley, LH
通讯作者：
Hurley, LH
DOI：
10.1523/jneurosci.0419-10.2010
发表时间：
2010-03-31
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cave JW;Akiba Y;Banerjee K;Bhosle S;Berlin R;Baker H
通讯作者：
Baker H