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首页> 外文期刊>Molecular and Cellular Biology >A directly repeated sequence in the beta-globin promoter regulates transcription in murine erythroleukemia cells.
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A directly repeated sequence in the beta-globin promoter regulates transcription in murine erythroleukemia cells.

机译：β-珠蛋白启动子中直接重复的序列调节鼠红白血病细胞中的转录。

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摘要

We have identified a previously undetected cis-acting element in the mouse beta-major globin promoter region that is necessary for maximal transcription levels of the gene in the inducible preerythroid murine erythroleukemia (MEL) cell line. This element, termed the beta-globin direct-repeat element (beta DRE), consists of a directly repeated 10-base-pair sequence, 5'-AGGGCAG(G)AGC-3', that lies just upstream from the TATA box of the promoter. The beta DRE motif is highly conserved in all adult mammalian beta-globin promoter sequences known. Mutation of either single repeat alone caused less than a twofold decrease in transcript levels. However, simultaneous mutation of both repeated regions resulted in a ninefold decrease in accumulated transcripts when the gene was transiently transfected into MEL cells. Attachment of the beta DRE to a heterologous promoter had little effect on levels of accumulated transcripts initiated from the promoter in undifferentiated MEL cells but resulted in a threefold increase in transcript levels in induced (differentiated) MEL cells. Similarly, a comparison of the relative effects of mutations in the beta DRE in uninduced and induced MEL cells indicated that the element was more active in induced cells. The increase in beta DRE activity upon MEL cell differentiation and the more pronounced effects of mutations in both repeats of the beta DRE have implications for the mechanism of action of the element in regulating beta-globin transcription and for mutational studies of other repetitive or redundant transcription elements.
机译：我们已经在小鼠β-主要球蛋白启动子区域中鉴定出一个先前未检测到的顺式作用元件，该元件对于诱导型前红系鼠红细胞白血病（MEL）细胞系中该基因的最大转录水平是必需的。该元件称为β-珠蛋白直接重复元件（beta DRE），由直接重复的10个碱基对的序列5'-AGGGCAG（G）AGC-3'组成，位于TATA框的上游启动子。在所有已知的成年哺乳动物β-珠蛋白启动子序列中，βDRE主题均高度保守。仅单个重复序列的突变就导致转录水平的下降少于两倍。但是，当基因被瞬时转染到MEL细胞中时，两个重复区域的同时突变导致累积的转录物减少了九倍。将βDRE附着到异源启动子上对未分化的MEL细胞中由该启动子启动的累积转录物水平几乎没有影响，但导致诱导（分化）的MEL细胞中转录物水平增加了三倍。同样，比较未诱导和诱导的MEL细胞中βDRE突变的相对影响，表明该元素在诱导的细胞中更具活性。 MEL细胞分化后βDRE活性的增加以及βDRE的两个重复序列中突变的更明显影响都对元素调节β珠蛋白转录的作用机理以及其他重复或冗余转录的突变研究产生了影响元素。

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