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Regulation of the cholinergic gene locus by the repressor element-1 silencing transcription factoreuron restrictive silencer factor (REST/NRSF) [Review]

机译:阻遏物1沉默转录因子/神经元限制性沉默子因子(REST / NRSF)对胆碱能基因基因座的调控[综述]

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摘要

The cholinergic gene locus is comprised of two genes, the choline acetyltransferase gene and the vesicular acetylcholine transporter gene. The vesicular acetylcholine transporter gene is located within the first intron of the choline acetyltransferase gene. This arrangement permits coordinate regulation of the locus. Protein kinase A regulates expression of the cholinergic gene locus in PC 12 cells. This regulation was found to be dependent on the presence of a 21-bp DNA sequence known as the repressor element-1 (RE-1)euron-restrictive silencer element (NRSE). Repressor element-1 silencing transcription factor (REST)euron-restrictive silencer factor (NRSF), which binds to the RE-1/NRSE, is a zinc finger containing transcriptional repressor that blocks the expression of many neuronal RE-1/NRSE containing genes in nonneuronal cells. However, REST/NRSF expression has also been observed in neurons as well as the PC 12 cell line used in these studies. REST/NRSF truncated isoforms were expressed in neuronal cells, suggesting they also function in regulating neuronal gene expression. A study of REST4, one of the REST/NRSF isoforms, suggests that it regulates transcription of the cholinergic gene locus by blocking the repressor activity of REST/NRSF. Protein kinase A regulation of the cholinergic gene locus in PC 12 cells can thus be attributed, at least in part, to increased synthesis of REST4, which in turn derepresses the repressor activity of REST/NRSF. (C) 2004 Elsevier Inc. All rights reserved. [References: 66]
机译:胆碱能基因基因座由两个基因组成,胆碱乙酰转移酶基因和囊泡乙酰胆碱转运蛋白基因。水泡乙酰胆碱转运蛋白基因位于胆碱乙酰转移酶基因的第一个内含子内。这种布置允许对基因座进行协调调节。蛋白激酶A调节PC 12细胞中胆碱能基因座的表达。发现这种调节依赖于21-bp DNA序列的存在,该序列被称为阻遏物1(RE-1)/神经元限制性沉默子(NRSE)。与RE-1 / NRSE结合的Repressor element-1沉默转录因子(REST)/神经元限制性沉默子因子(NRSF)是含锌指的转录阻遏物,可阻止许多神经元RE-1 / NRSE的表达非神经细胞中的基因。但是,在这些研究中使用的神经元以及PC 12细胞系中也观察到REST / NRSF表达。 REST / NRSF截短的亚型在神经元细胞中表达,表明它们在调节神经元基因表达中也起作用。对REST4(一种REST / NRSF异构体)的研究表明,它可通过阻断REST / NRSF的阻遏物活性来调节胆碱能基因座的转录。因此,PC 12细胞中胆碱能基因基因座的蛋白激酶A调节至少可以部分归因于REST4合成的增加,进而降低了REST / NRSF的阻遏物活性。 (C)2004 Elsevier Inc.保留所有权利。 [参考:66]

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