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纯化的糖皮质激素受体在体外选择性地与一个克隆的DNA片段结合,该片段在体内介导对糖皮质激素的延迟性二次反应。

Purified glucocorticoid receptors bind selectively in vitro to a cloned DNA fragment that mediates a delayed secondary response to glucocorticoids in vivo.

作者信息

Hess P, Meenakshi T, Chan G C, Carlstedt-Duke J, Gustafsson J A, Payvar F

机构信息

E. A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, MO 63104.

出版信息

Proc Natl Acad Sci U S A. 1990 Apr;87(7):2564-8. doi: 10.1073/pnas.87.7.2564.

DOI:10.1073/pnas.87.7.2564
PMID:1690888
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC53730/
Abstract

We have identified and characterized a 206-base-pair region downstream from rat alpha 2u-globulin promoter that specifically mediates a delayed secondary response to glucocorticoids. Unlike positive primary glucocorticoid response elements (GREs), this regulatory element, termed delayed sGRE, dictates an inductive process preceded by a time lag of several hours and blocked by the protein synthesis inhibitor cycloheximide. Reminiscent of GREs and negative GREs (nGREs), a delayed sGRE confers hormonal regulation upon a linked heterologous promoter from a downstream position with respect to transcription start site and, remarkably, also interacts selectively with purified glucocorticoid receptor. These results imply that receptor binding to a delayed sGRE in vivo may mediate certain secondary responses to glucocorticoid hormones.

摘要

我们已经鉴定并表征了大鼠α2u-球蛋白启动子下游一个206个碱基对的区域,该区域特异性介导对糖皮质激素的延迟二次应答。与阳性原发性糖皮质激素反应元件(GREs)不同,这个被称为延迟sGRE的调节元件决定了一个诱导过程,该过程之前有几个小时的时间延迟,并被蛋白质合成抑制剂环己酰亚胺阻断。与GREs和负性GREs(nGREs)类似,延迟sGRE从转录起始位点的下游位置赋予连接的异源启动子激素调节,并且值得注意的是,它还与纯化的糖皮质激素受体选择性相互作用。这些结果表明,体内受体与延迟sGRE的结合可能介导对糖皮质激素的某些二次应答。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5887/53730/c6aaae03a410/pnas01032-0193-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5887/53730/f531325d73bf/pnas01032-0191-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5887/53730/f5b18cdcb7c0/pnas01032-0191-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5887/53730/5b92f5ae1f4d/pnas01032-0192-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5887/53730/30dc787bb8c5/pnas01032-0193-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5887/53730/c6aaae03a410/pnas01032-0193-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5887/53730/f531325d73bf/pnas01032-0191-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5887/53730/f5b18cdcb7c0/pnas01032-0191-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5887/53730/5b92f5ae1f4d/pnas01032-0192-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5887/53730/30dc787bb8c5/pnas01032-0193-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5887/53730/c6aaae03a410/pnas01032-0193-b.jpg

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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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The sequences of an expressed rat alpha-tubulin gene and a pseudogene with an inserted repetitive element.一个表达的大鼠α-微管蛋白基因和一个插入重复元件的假基因的序列。
Nature. 1982 Nov 25;300(5890):330-5. doi: 10.1038/300330a0.
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Sequence-specific binding of glucocorticoid receptor to MTV DNA at sites within and upstream of the transcribed region.
糖皮质激素受体与转录区域内及上游位点的MTV DNA发生序列特异性结合。
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The glucocorticoid receptor binds to defined nucleotide sequences near the promoter of mouse mammary tumour virus.糖皮质激素受体与小鼠乳腺肿瘤病毒启动子附近特定的核苷酸序列结合。
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Multiple specific binding sites for purified glucocorticoid receptors on mammary tumor virus DNA.纯化的糖皮质激素受体在乳腺肿瘤病毒DNA上的多个特异性结合位点。
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DNA sequences required for hormonal induction of rat alpha 2u-globulin genes.激素诱导大鼠α2u-球蛋白基因所需的DNA序列。
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DNA sequences bound specifically by glucocorticoid receptor in vitro render a heterologous promoter hormone responsive in vivo.在体外与糖皮质激素受体特异性结合的DNA序列,在体内可使异源启动子对激素产生反应。
Cell. 1983 Jun;33(2):489-99. doi: 10.1016/0092-8674(83)90430-0.
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