Individual stage selector element mutations lead to reciprocal changes in beta- vs. epsilon-globin gene transcription: genetic confirmation of promoter competition during globin gene switching.
Individual stage selector element mutations lead to reciprocal changes in beta- vs. epsilon-globin gene transcription: genetic confirmation of promoter competition during globin gene switching.
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各个阶段选择器元件突变导致β珠蛋白基因转录与ε珠蛋白基因转录的相互变化：珠蛋白基因转换过程中启动子竞争的遗传确认。
作者：
Kevin P. Foley;J. D. Engel
对鸡胚胎到成年 β 样珠蛋白基因转换的生化和遗传分析得出这样的假设：顺式连接的 ε 和 β 珠蛋白基因的启动子之间与共享增强子相互作用的竞争介导了 β 珠蛋白同种型表达的发育变化。为了测试该启动子竞争模型的具体预测，使用灵敏的RNA/聚合酶链反应测定来研究单个β-珠蛋白启动子突变对瞬时转染的红细胞中两个连锁基因表达的影响。减弱成人β珠蛋白转录的突变同时导致胚胎ε珠蛋白基因的表达成比例增加。与该模型一致，破坏两个成体阶段特异性转录因子（NF-E4和β CTF）结合位点的突变表明，这些位点对于诱导β珠蛋白基因表达和间接抑制（通过启动子竞争）终形（成体）红系细胞中的ε珠蛋白转录至关重要。这些结果提供了直接证据，表明阶段特异性转录因子影响多个相互作用的珠蛋白顺式调节元件之间存在的平衡。我们得出的结论是，启动子竞争是实现鸡β-珠蛋白基因转换发育调节的重要机制，并且这种竞争性相互作用可能被证明普遍适用于各种其他时间或空间限制基因表达模式的调节。
Biochemical and genetic analysis of the embryonic to adult beta-like globin gene switch in chickens has led to the hypothesis that competition between the promoters of the cis-linked epsilon- and beta-globin genes for interaction with a shared enhancer mediates the developmental changes in expression of beta-globin protein isotypes. To test specific predictions of this promoter competition model, a sensitive RNA/polymerase chain reaction assay has been used to investigate the effects of individual beta-globin promoter mutations on expression of the two linked genes in transiently transfected erythroid cells. Mutations that attenuated adult beta-globin transcription resulted concomitantly in a proportional increase in expression of the embryonic epsilon-globin gene. Consistent with the model, mutations disrupting the binding sites for either of two adult stage-specific transcription factors (NF-E4 and beta CTF) indicate that these sites are essential both for induction of beta-globin gene expression and for indirect suppression (through promoter competition) of epsilon-globin transcription in definitive (adult) erythroid cells. These results provide direct evidence that stage-specific transcription factors affect the equilibrium existing between multiple interacting globin cis-regulatory elements. We conclude that promoter competition is an important mechanism through which developmental regulation of chicken beta-globin gene switching is achieved and that such competitive interactions may prove to be generally applicable to the regulation of a variety of other temporally or spatially restricted gene expression patterns.
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.81.9.2718
发表时间：
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期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
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DOI：
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发表时间：
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期刊：
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影响因子：
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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DOI：
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发表时间：
1990-04-01
影响因子：
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作者：
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