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胎儿γ-珠蛋白基因或胚胎ζ-珠蛋白基因5'端的DNA序列对K562细胞中人β-珠蛋白启动子的激活作用。

Activation of the human beta-globin promoter in K562 cells by DNA sequences 5' to the fetal gamma- or embryonic zeta-globin genes.

作者信息

Lin H J, Anagnou N P, Rutherford T R, Shimada T, Nienhuis A W

出版信息

J Clin Invest. 1987 Aug;80(2):374-80. doi: 10.1172/JCI113082.

DOI:10.1172/JCI113082
PMID:3611352
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC442247/
Abstract

Regulatory sequences of the human fetal gamma-globin gene were studied by constructing composite gamma/beta globin promoters and comparing their function to that of intact beta promoters in human K562 cells. The beta-globin gene with either 1,600 or 127 basepairs of beta promoter sequence was not expressed after stable introduction into K562 cells, consistent with the known inactivity of the beta-globin gene in these cells. In contrast, a gamma/beta promoter composed of a gamma fragment spanning positions -408 to -137 joined to the 127-bp beta promoter was able to drive the beta-globin gene. The gene appeared to be inducible with hemin. A zeta-globin 5' flanking fragment also activated the beta promoter. The function of a series of composite gamma/beta promoters was then assessed by their ability to drive directly the neomycin resistance gene, again in stably transformed cells. The -408 to -137 gamma fragment activated the beta promoter in an orientation-specific manner in this assay. Deletion analysis showed that regulatory sequences were present between positions -259 and -137 of the fetal gamma-globin gene flanking region.

摘要

通过构建复合γ/β珠蛋白启动子并将其功能与完整β启动子在人K562细胞中的功能进行比较，研究了人胎儿γ-珠蛋白基因的调控序列。带有1600或127个碱基对β启动子序列的β-珠蛋白基因在稳定导入K562细胞后未表达，这与这些细胞中β-珠蛋白基因已知的无活性一致。相比之下，由跨越-408至-137位的γ片段与127bp的β启动子连接而成的γ/β启动子能够驱动β-珠蛋白基因。该基因似乎可被血红素诱导。ζ-珠蛋白5'侧翼片段也激活了β启动子。然后通过一系列复合γ/β启动子在稳定转化细胞中直接驱动新霉素抗性基因的能力来评估它们的功能。在该试验中，-408至-137γ片段以方向特异性方式激活了β启动子。缺失分析表明，在胎儿γ-珠蛋白基因侧翼区域的-259和-137位之间存在调控序列。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6201/442247/22eb8f611d11/jcinvest00092-0105-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6201/442247/915f485651c2/jcinvest00092-0105-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6201/442247/798be7685d22/jcinvest00092-0105-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6201/442247/87ece287dee2/jcinvest00092-0105-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6201/442247/22eb8f611d11/jcinvest00092-0105-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6201/442247/915f485651c2/jcinvest00092-0105-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6201/442247/798be7685d22/jcinvest00092-0105-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6201/442247/87ece287dee2/jcinvest00092-0105-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6201/442247/22eb8f611d11/jcinvest00092-0105-d.jpg

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引用本文的文献

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本文引用的文献

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Beta Thalassemia: mutations which affect processing of the beta-Globin mRNA precursor.β地中海贫血：影响β-珠蛋白mRNA前体加工的突变。
Cell. 1980 Aug;21(1):149-57. doi: 10.1016/0092-8674(80)90122-1.
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RNA processing errors in patients with beta-thalassemia.β地中海贫血患者的RNA加工错误。
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Abundance and structure of globin mRNA in K562 human leukemia cells.K562人白血病细胞中珠蛋白mRNA的丰度和结构
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Mutations in two regions upstream of the A gamma globin gene canonical promoter affect gene expression.γ珠蛋白基因典型启动子上游两个区域的突变会影响基因表达。
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A 46 base pair enhancer sequence within the locus activating region is required for induced expression of the gamma-globin gene during erythroid differentiation.在红细胞分化过程中，γ-珠蛋白基因的诱导表达需要基因座激活区域内一段46个碱基对的增强子序列。
Nucleic Acids Res. 1990 May 11;18(9):2721-31. doi: 10.1093/nar/18.9.2721.
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Roles of fetal G gamma-globin promoter elements and the adult beta-globin 3' enhancer in the stage-specific expression of globin genes.胎儿γ-珠蛋白启动子元件和成人β-珠蛋白3'增强子在珠蛋白基因阶段特异性表达中的作用。
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Inducibility of the HS II enhancer depends on binding of an erythroid specific nuclear protein.HS II增强子的可诱导性取决于一种红细胞特异性核蛋白的结合。
Nucleic Acids Res. 1990 Oct 25;18(20):6011-7. doi: 10.1093/nar/18.20.6011.
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A naturally occurring gamma globin gene mutation enhances SP1 binding activity.一种自然发生的γ珠蛋白基因突变增强了SP1结合活性。
Mol Cell Biol. 1990 Jan;10(1):95-102. doi: 10.1128/mcb.10.1.95-102.1990.
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Functional profile of the human fetal gamma-globin gene upstream promoter region.人类胎儿γ-珠蛋白基因上游启动子区域的功能概况
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10
Identification of a stage selector element in the human gamma-globin gene promoter that fosters preferential interaction with the 5' HS2 enhancer when in competition with the beta-promoter.在人γ-珠蛋白基因启动子中鉴定出一个阶段选择元件，当与β-启动子竞争时，该元件促进与5' HS2增强子的优先相互作用。
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Erythroleukemia (K562) cells contain a functional beta-globin gene.红白血病（K562）细胞含有一个功能性β-珠蛋白基因。
Mol Cell Biol. 1984 Nov;4(11):2553-5. doi: 10.1128/mcb.4.11.2553-2555.1984.
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Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation.通过电穿孔导入小鼠前B淋巴细胞的人κ免疫球蛋白基因的增强子依赖性表达。
Proc Natl Acad Sci U S A. 1984 Nov;81(22):7161-5. doi: 10.1073/pnas.81.22.7161.
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Specific factor conferring nuclease hypersensitivity at the 5' end of the chicken adult beta-globin gene.赋予鸡成年β-珠蛋白基因5'端核酸酶超敏感性的特定因子。
Proc Natl Acad Sci U S A. 1984 Jan;81(1):95-9. doi: 10.1073/pnas.81.1.95.
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Inducible transcription of five globin genes in K562 human leukemia cells.K562人白血病细胞中五个珠蛋白基因的可诱导转录。
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Three regions upstream from the cap site are required for efficient and accurate transcription of the rabbit beta-globin gene in mouse 3T6 cells.兔β-珠蛋白基因在小鼠3T6细胞中高效且准确转录需要帽位点上游的三个区域。
Cell. 1983 Mar;32(3):695-706. doi: 10.1016/0092-8674(83)90055-7.
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Differences in human alpha-, beta- and delta-globin gene expression in monkey kidney cells.猴肾细胞中人类α、β和δ珠蛋白基因表达的差异。
Cell. 1982 Aug;30(1):173-83. doi: 10.1016/0092-8674(82)90023-x.
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Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter.利用处于SV40早期区域启动子控制下的细菌基因将哺乳动物细胞转化为抗生素抗性细胞。
J Mol Appl Genet. 1982;1(4):327-41.