DNA Binding Site Sequence Directs Glucocorticoid Receptor Structure and Activity

被引：528

作者：

Meijsing, Sebastiaan H. ^{[1
]}

Pufall, Miles A. ^{[1
]}

So, Alex Y. ^{[1
,2
]}

Bates, Darren L. ^{[3
]}

Chen, Lin ^{[3
]}

Yamamoto, Keith R. ^{[1
,2
]}

机构：

[1] Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94158 USA

[2] Univ Calif San Francisco, Chem & Chem Biol Program, San Francisco, CA 94107 USA

[3] Univ So Calif, Dept Mol & Computat Biol, Los Angeles, CA 90089 USA

来源：

SCIENCE | 2009年 / 324卷 / 5925期

关键词：

RESPONSE ELEMENTS; NUCLEAR RECEPTOR; GENE; EXPRESSION; REPRESSION; MOTIF;

D O I：

10.1126/science.1164265

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Genes are not simply turned on or off, but instead their expression is fine-tuned to meet the needs of a cell. How genes are modulated so precisely is not well understood. The glucocorticoid receptor (GR) regulates target genes by associating with specific DNA binding sites, the sequences of which differ between genes. Traditionally, these binding sites have been viewed only as docking sites. Using structural, biochemical, and cell-based assays, we show that GR binding sequences, differing by as little as a single base pair, differentially affect GR conformation and regulatory activity. We therefore propose that DNA is a sequence-specific allosteric ligand of GR that tailors the activity of the receptor toward specific target genes.

引用

页码：407 / 410

页数：4

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