Widespread Negative Response Elements Mediate Direct Repression by Agonist-Liganded Glucocorticoid Receptor

被引：409

作者：

Surjit, Milan ^{[1
]}

Ganti, Krishna Priya ^{[1
]}

Mukherji, Atish ^{[1
]}

Ye, Tao ^{[1
]}

Hua, Guoqiang ^{[1
]}

Metzger, Daniel ^{[1
]}

Li, Mei ^{[1
]}

Chambon, Pierre ^{[1
]}

机构：

[1] Univ Strasbourg, CNRS, Inst Genet & Biol Mol & Cellulaire, Coll France,Inserm U964,UMR7104, F-67404 Illkirch Graffenstaden, France

来源：

CELL | 2011年 / 145卷 / 02期

关键词：

REV-ERB-ALPHA; MOUSE KERATINOCYTES; GENE PROMOTER; BINDING; MICE; MECHANISMS; GROWTH; TRANSACTIVATION; TRANSREPRESSION; TRANSCRIPTION;

D O I：

10.1016/j.cell.2011.03.027

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The glucocorticoid (GC) receptor (GR), when liganded to GC, activates transcription through direct binding to simple (+)GRE DNA binding sequences (DBS). GC-induced direct repression via GR binding to complex "negative" GREs (nGREs) has been reported. However, GR-mediated transrepression was generally ascribed to indirect "tethered" interaction with other DNA-bound factors. We report that GC-induces direct transrepression via the binding of GR to simple DBS (IR nGREs) unrelated to (+) GRE. These DBS act on agonist-liganded GR, promoting the assembly of cis-acting GR-SMRT/NCoR repressing complexes. IR nGREs are present in over 1000 mouse/human ortho-log genes, which are repressed by GC in vivo. Thus variations in the levels of a single ligand can coordinately turn genes on or off depending in their response element DBS, allowing an additional level of regulation in GR signaling. This mechanism suits GR signaling remarkably well, given that adrenal secretion of GC fluctuates in a circadian and stress-related fashion.

引用

页码：224 / 241

页数：18

共 61 条

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