Identification of CTCF as a master regulator of the clustered protocadherin genes.
Identification of CTCF as a master regulator of the clustered protocadherin genes.
复制标题
将CTCF鉴定为聚集的原钙粘着蛋白基因的主要调节剂。
DOI：
10.1093/nar/gkr1260
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发表时间：
2012-04
影响因子：
14.9
通讯作者：
Shapiro E
中科院分区：
文献类型：
--
作者：
Golan-Mashiach M;Grunspan M;Emmanuel R;Gibbs-Bar L;Dikstein R;Shapiro E
大脑是一个庞大而复杂的神经元网络。特异性神经元连接被认为是基于52种原钙粘蛋白（Pcdh）膜粘附蛋白的组合表达，其中每个神经元仅表达特定的子集。Pcdh基因串联排列，形成Pcdhα、Pcdhβ和Pcdhγ三个家族。每个Pcdh基因的表达受具有所有52个基因共有的调控保守序列元件（CSE）的启动子调控。Pcdh基因表达的调控机制和调控因素目前尚不清楚。在这里，我们表明，每个Pcdh基因的启动子包含一个基因特异性的保守控制区，称为特定序列元件（SSE），位于相邻和上游的CSE和激活转录与CSE。我们纯化了特异性结合SSE-CSE区域的复合物，并将CCTC结合因子（CTCF）鉴定为结合并激活Pcdh启动子的关键分子。我们的研究结果指出，CTCF作为一个必不可少的因素Pcdh的表达，并可能管理神经元的连接。
The brain is a large and complex network of neurons. Specific neuronal connectivity is thought to be based on the combinatorial expression of the 52 protocadherins (Pcdh) membrane adhesion proteins, whereby each neuron expresses only a specific subset. Pcdh genes are arranged in tandem, in a cluster of three families: Pcdhα, Pcdhβ and Pcdhγ. The expression of each Pcdh gene is regulated by a promoter that has a regulatory conserved sequence element (CSE), common to all 52 genes. The mechanism and factors controlling individual Pcdh gene expression are currently unknown. Here we show that the promoter of each Pcdh gene contains a gene-specific conserved control region, termed specific sequence element (SSE), located adjacent and upstream to the CSE and activates transcription together with the CSE. We purified the complex that specifically binds the SSE–CSE region and identified the CCTC binding-factor (CTCF) as a key molecule that binds and activates Pcdh promoters. Our findings point to CTCF as a factor essential for Pcdh expression and probably governing neuronal connectivity.
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