CoREST:: A functional corepressor required for regulation of neural-specific gene expression
CoREST:: A functional corepressor required for regulation of neural-specific gene expression
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DOI：
10.1073/pnas.96.17.9873
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发表时间：
1999-08-17
影响因子：
11.1
通讯作者：
Mandel, G
中科院分区：
文献类型：
--
作者：
Andrés, ME;Burger, C;Mandel, G
几种编码对神经元表型至关重要的蛋白质的基因，如脑II型钠通道基因，仅在神经元中高水平表达。这种细胞特异性部分是由于阻遏蛋白REST/NRSF（RE 1沉默转录因子/中性-限制性沉默因子）介导的非神经细胞中的长期抑制。我们在这里表明，CoREST，一个新发现的人类蛋白质，作为一个辅助抑制REST的功能。REST中的单个锌指基序是CoREST相互作用所必需的。破坏结合的基序突变也消除了抑制。当与Ga 14 DNA结合结构域融合时，CoREST作为阻遏物发挥作用，CoREST存在于表达REST的细胞系中，并且蛋白质存在于相同的免疫复合物中。CorREST包含两个SANT（SW 13/ADA 2/NCoR/TFIIII B B）结构域，其是类维生素A和甲状腺人受体（SMRT）延伸的辅阻遏物的核受体和沉默介体的结构特征，所述辅阻遏物介导类固醇激素受体的诱导型阻遏。REST和CoREST一起介导非神经细胞中II型钠通道启动子的阻遏，REST/CoREST复合物可能介导维持细胞身份所必需的长期抑制。
Several genes encoding proteins critical to the neuronal phenotype, such as the brain type II sodium channel gene, are expressed to high levels only in neurons. This cell specificity is due, in part, to long-term repression in nonneural cells mediated by the repressor protein REST/NRSF (RE1 silencing transcription factor/neutral-restrictive silencing factor). We show here that CoREST, a newly identified human protein, functions as a corepressor for REST. A single zinc finger motif in REST is required for CoREST interaction. Mutations of the motif that disrupt binding also abrogate repression. When fused to a Ga14 DNA-binding domain, CoREST functions as a repressor, CoREST is present in cell lines that express REST, and the proteins are found in the same immunocomplex. CoREST contains two SANT (SW13/ADA2/NCoR/TFIIIB B) domains, a structural feature of the nuclear receptor and silencing mediator for retinoid and thyroid human receptors (SMRT)-extended corepressors that mediate inducible repression by steroid hormone receptors, Together, REST and CoREST mediate repression of the type II sodium channel promoter in nonneural cells, and the REST/CoREST complex may mediate long-term repression essential to maintenance of cell identity.