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人类胎儿γ-珠蛋白基因上游启动子区域的功能概况

Functional profile of the human fetal gamma-globin gene upstream promoter region.

作者信息

Lin H J, Han C Y, Nienhuis A W

机构信息

Department of Pediatrics, Harbor-UCLA Medical Center, Torrance 90502.

出版信息

Am J Hum Genet. 1992 Aug;51(2):363-70.

PMID:1642236
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1682667/
Abstract

We performed a systematic functional analysis of the human gamma-globin promoter to identify its activator domains. We used a panel of truncation and scanning mutants as well as transfection in human K562 fetal erythroid cells. The various mutations produced relatively small changes in promoter function in both transient and stable transfection assays. The CACCC region and the region containing the binding sites for protein GATA-1 behaved as activator domains. We also obtained evidence for a minor activator site in the - 200 to - 190 region. The results are consistent with the interpretation that gamma-globin gene regulation may occur in part through multiple small effects of promoter elements.

摘要

我们对人γ-珠蛋白启动子进行了系统的功能分析,以确定其激活结构域。我们使用了一系列截短和扫描突变体,并在人K562胎儿红系细胞中进行转染。在瞬时和稳定转染实验中,各种突变在启动子功能上产生了相对较小的变化。CACCC区域和包含蛋白GATA-1结合位点的区域表现为激活结构域。我们还获得了在-200至-190区域存在一个次要激活位点的证据。这些结果与γ-珠蛋白基因调控可能部分通过启动子元件的多种小效应发生的解释一致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8077/1682667/16a0fefcee1d/ajhg00066-0143-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8077/1682667/16a0fefcee1d/ajhg00066-0143-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8077/1682667/16a0fefcee1d/ajhg00066-0143-a.jpg

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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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2
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The erythroid Krüppel-like factor transactivation domain is a critical component for cell-specific inducibility of a beta-globin promoter.红系类Krüppel样因子反式激活结构域是β-珠蛋白启动子细胞特异性诱导的关键组成部分。
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Functional erythroid promoters created by interaction of the transcription factor GATA-1 with CACCC and AP-1/NFE-2 elements.由转录因子GATA-1与CACCC以及AP-1/NFE-2元件相互作用产生的功能性红系启动子。
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FKLF, a novel Krüppel-like factor that activates human embryonic and fetal beta-like globin genes.FKLF,一种激活人类胚胎和胎儿类β珠蛋白基因的新型Krüppel样因子。
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本文引用的文献

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Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.在哺乳动物细胞中表达氯霉素乙酰转移酶的重组基因组。
Mol Cell Biol. 1982 Sep;2(9):1044-51. doi: 10.1128/mcb.2.9.1044-1051.1982.
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G gamma beta+ hereditary persistence of fetal hemoglobin: cosmid cloning and identification of a specific mutation 5' to the G gamma gene.Gγβ⁺遗传性胎儿血红蛋白持续存在:黏粒克隆及Gγ基因5'端特定突变的鉴定
Proc Natl Acad Sci U S A. 1984 Aug;81(15):4894-8. doi: 10.1073/pnas.81.15.4894.
5
An enhancer element lies 3' to the human A gamma globin gene.一个增强子元件位于人类Aγ珠蛋白基因的3'端。
EMBO J. 1987 Oct;6(10):2997-3004. doi: 10.1002/j.1460-2075.1987.tb02605.x.
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Position-independent, high-level expression of the human beta-globin gene in transgenic mice.人β-珠蛋白基因在转基因小鼠中与位置无关的高水平表达。
Cell. 1987 Dec 24;51(6):975-85. doi: 10.1016/0092-8674(87)90584-8.
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Activation of the human beta-globin promoter in K562 cells by DNA sequences 5' to the fetal gamma- or embryonic zeta-globin genes.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。
J Clin Invest. 1987 Aug;80(2):374-80. doi: 10.1172/JCI113082.
8
Human globin gene promoter sequences are sufficient for specific expression of a hybrid gene transfected into tissue culture cells.人类珠蛋白基因启动子序列足以使转染到组织培养细胞中的杂交基因实现特异性表达。
Mol Cell Biol. 1987 Jan;7(1):398-402. doi: 10.1128/mcb.7.1.398-402.1987.
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Expression of a human placental alkaline phosphatase gene in transfected cells: use as a reporter for studies of gene expression.人胎盘碱性磷酸酶基因在转染细胞中的表达:用作基因表达研究的报告基因。
Proc Natl Acad Sci U S A. 1988 Sep;85(17):6342-6. doi: 10.1073/pnas.85.17.6342.
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Promoter sequences required for function of the human gamma globin gene in erythroid cells.人类γ珠蛋白基因在红细胞中发挥功能所需的启动子序列。
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