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一种新的Cys2/His2锌指基因rKr2在分化的大鼠少突胶质细胞中表达,并编码一种具有功能性阻遏结构域的蛋白质。

A new Cys2/His2 zinc finger gene, rKr2, is expressed in differentiated rat oligodendrocytes and encodes a protein with a functional repressor domain.

作者信息

Pott U, Thiesen H J, Colello R J, Schwab M E

机构信息

Brain Research Institute, University of Zurich, Switzerland.

出版信息

J Neurochem. 1995 Nov;65(5):1955-66. doi: 10.1046/j.1471-4159.1995.65051955.x.

Abstract

The function of the vertebrate nervous system is dependent on the proper myelination of its fiber tracts. Myelin of the CNS is produced by oligodendrocytes. To identify gene regulatory proteins expressed in this particular glial cell type, we isolated cDNAs coding for Cys2/His2 zinc finger proteins from a rat oligodendrocyte cDNA library. One clone, named rKr2 (rKr for rat Krüppel-type protein), encodes a protein with 19 carboxy-terminal zinc finger domains and an amino-terminal Krüppel-associated box domain. This amino-terminal domain of the rKr2 protein behaved as a strong transcriptional repressor module when fused to the DNA binding domain of yeast GAL4 and tested on an appropriate reporter construct. High levels of rKr2 mRNA in adult rat tissues were found only in the CNS and testis; in the CNS, the message was predominantly expressed in differentiated oligodendrocytes. The modular structure of the rKr2 protein (carboxy-terminal DNA binding domain, amino-terminal repressor module) and its expression pattern suggest that it acts as a sequence-specific transcriptional repressor in the myelin-producing glial cells of the CNS.

摘要

脊椎动物神经系统的功能依赖于其纤维束的正常髓鞘形成。中枢神经系统(CNS)的髓鞘由少突胶质细胞产生。为了鉴定在这种特定神经胶质细胞类型中表达的基因调控蛋白,我们从大鼠少突胶质细胞cDNA文库中分离出编码Cys2/His2锌指蛋白的cDNA。一个名为rKr2(大鼠Krüppel型蛋白的rKr)的克隆编码一种具有19个羧基末端锌指结构域和一个氨基末端Krüppel相关框结构域的蛋白。当rKr2蛋白的这个氨基末端结构域与酵母GAL4的DNA结合结构域融合,并在合适的报告基因构建体上进行测试时,它表现为一个强大的转录抑制模块。在成年大鼠组织中,仅在中枢神经系统和睾丸中发现高水平的rKr2 mRNA;在中枢神经系统中,该信使主要在分化的少突胶质细胞中表达。rKr2蛋白的模块化结构(羧基末端DNA结合结构域,氨基末端抑制模块)及其表达模式表明,它在中枢神经系统产生髓鞘的神经胶质细胞中作为序列特异性转录抑制因子发挥作用。

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