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首页> 外文期刊>Nucleic Acids Research >MULTIPLE REGIONS OF P45 NF-E2 ARE REQUIRED FOR BETA-GLOBIN GENE EXPRESSION IN ERYTHROID CELLS
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MULTIPLE REGIONS OF P45 NF-E2 ARE REQUIRED FOR BETA-GLOBIN GENE EXPRESSION IN ERYTHROID CELLS

机译：在红细胞中表达β-球蛋白基因需要多个区域的P45 NF-E2

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摘要

Regulated expression of genes in the beta-globin cluster depends upon sequences located between 5 and 20 kb upstream of the epsilon gene, known as the locus control region (LCR). beta-Globin expression in murine erythroleukemia (MEL) cells depends on NF-E2, a transcription factor which binds to enhancer sequences in the LCR. To gain insight into the mechanism of globin gene activation by NF-E2, an NF-E2 null MEL cell line was used to map regions of NF-E2 required for beta-globin expression. Within the transactivation domain, two discrete proline-rich regions were required for rescue of beta-globin expression. The first was located at the N-terminus of NF-E2, while the second was located N-terminal of the cap 'n collar (CNC) domain. Other proline-rich sequences were dispensable, indicating that proline content per se does not determine NF-E2 activity. Mutations within the conserved CNC domain markedly diminished rescue of beta-globin expression. This domain was required, in addition to the basic leucine zipper domain, for DNA binding activity. The requirement for discrete proline-rich sequences within the transactivation domain suggests that globin gene expression in MEL cells depends on specific interactions between NF-E2 and downstream effector molecules.
机译：β-珠蛋白簇中基因的调控表达取决于位于ε基因上游5至20 kb之间的序列，称为基因座控制区（LCR）。鼠红白血病（MEL）细胞中的β-球蛋白表达取决于NF-E2，NF-E2是与LCR中增强子序列结合的转录因子。为了深入了解NF-E2激活球蛋白基因的机制，使用了NF-E2空MEL细胞系来绘制β-球蛋白表达所需的NF-E2区域。在反式激活域内，需要两个离散的富含脯氨酸的区域来挽救β-珠蛋白的表达。第一个位于NF-E2的N端，而第二个位于cap'n衣领（CNC）域的N端。其他富含脯氨酸的序列是可有可无的，表明脯氨酸含量本身并不决定NF-E2活性。保守的CNC域内的突变显着减少了β-珠蛋白表达的拯救。除了基本的亮氨酸拉链结构域之外，该结构域对于DNA结合活性也是必需的。在反式激活域内对富含脯氨酸的序列的要求表明，MEL细胞中的球蛋白基因表达取决于NF-E2与下游效应分子之间的特异性相互作用。

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