Neuronal restrictive silencing element is found in the KCC2 gene: Molecular basis for KCC2-Specific expression in neurons
Neuronal restrictive silencing element is found in the KCC2 gene: Molecular basis for KCC2-Specific expression in neurons
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DOI：
10.1152/jn.2001.85.2.995
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发表时间：
2001-02-01
影响因子：
2.5
通讯作者：
Delpire, E
中科院分区：
文献类型：
--
作者：
Karadsheh, MF;Delpire, E
KCC 2是K-Cl协同转运蛋白的四种已知亚型之一，其表达模式仅限于神经元。它介导Cl-穿过神经元膜的外排，并在GABA能和甘氨酸能神经传递中起重要作用。为了理解KCC 2表达的神经元特异性的分子基础，我们分离并测序了KCC 2基因的部分，包括其5'侧翼（对照）区域的一些。我们发现了一个21 bp的序列，内含子1内，共享80%的同源性的共识网站神经元限制性沉默因子的结合。我们证明，这种特定的序列的KCC 2基因促进转录调控显示，从小鼠神经前体细胞系分离的核蛋白与此21 bp的元件相互作用，并通过建立该元件沉默报告基因在非神经元细胞的表达。
KCC2 is one of four known isoforms of the K-Cl cotransporter with an expression pattern restricted to neurons. It mediates efflux of Cl- across neuronal membranes and plays an important role in GABAergic and glycinergic neurotransmission. To understand the molecular basis for neuronal specificity of KCC2 expression, we isolated and sequenced portions of the KCC2 gene, including some of its 5' flanking (control) region. We found a 21-bp sequence, within intron 1, that shares 80% homology to the consensus site for neuronal-restrictive silencing factor binding. We demonstrated that this specific sequence of the KCC2 gene promotes transcriptional regulation by showing that nuclear proteins isolated from a mouse neural progenitor cell line interact with this 21-bp element and by establishing that this element silences reporter gene expression in nonneuronal cells.