The neuronal microtubule-associated protein 1B is under homeoprotein transcriptional control
The neuronal microtubule-associated protein 1B is under homeoprotein transcriptional control
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DOI：
10.1523/jneurosci.21-10-03350.2001
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发表时间：
2001-05-15
影响因子：
5.3
通讯作者：
Volovitch, M
中科院分区：
文献类型：
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作者：
Montesinos, ML;Foucher, I;Volovitch, M
为了鉴定在出生后神经元中受同源异型蛋白转录因子调控的基因，将Engrailed同源异型蛋白的DNA结合域（同源异型域）内化到大鼠小脑神经元中。内化的同源结构域（EnHD）充当Engrailed和几种同源蛋白的竞争性抑制剂（Mainguy等人，2000）。差异显示分析显示，微管相关蛋白1B（MAP1B）mRNA的上调EnHD。这种上调不需要蛋白质合成，表明同源结构域对MAP1B转录的直接影响。将MAP1B的启动子区切割成几个亚结构域，并测试每个亚结构域结合Engrailed和EnHD以及与含有Engrailed的小脑核提取物结合的能力。此外，通过鸡胚神经管中的电穿孔，在体内评价每个亚结构域和整个启动子的活性和Engrailed的调节。这些实验证明MAP1B启动子在体内受Engrailed调控。此外，他们表明，一个启动子结构域，其中包含所有的ATTA同源蛋白同源结合位点共同的大鼠和人类基因是一个必不可少的因素，这种调节。因此，MAP1B是一种参与神经元生长和再生的细胞骨架蛋白，受同源异型蛋白的转录调控。
To identify genes regulated by homeoprotein transcription factors in postnatal neurons, the DNA-binding domain (homeodomain) of Engrailed homeoprotein was internalized into rat cerebellum neurons. The internalized homeodomain (EnHD) acts as a competitive inhibitor of Engrailed and of several homeoproteins (Mainguy et al., 2000). Analysis by differential display revealed that microtubule-associated protein 1B (MAP1B) mRNA is upregulated by EnHD. This upregulation does not require protein synthesis, suggesting a direct effect of the homeodomain on MAP1B transcription. The promoter region of MAP1B was cut into several subdomains, and each subdomain was tested for its ability to bind Engrailed and EnHD and to associate with Engrailed-containing cerebellum nuclear extracts. In addition, the activity, and regulation by Engrailed, of each subdomain and of the entire promoter were evaluated in vivo by electroporation in the chick embryo neural tube. These experiments demonstrate that MAP1B promoter is regulated by Engrailed in vivo. Moreover, they show that one promoter domain that contains all ATTA homeoprotein cognate binding sites common to the rat and human genes is an essential element of this regulation. It is thus proposed that MAP1B, a cytoskeleton protein involved in neuronal growth and regeneration, is under homeoprotein transcriptional regulation.