The Regulatory T Cell Lineage Factor Foxp3 Regulates Gene Expression through Several Distinct Mechanisms Mostly Independent of Direct DNA Binding

被引：40

作者：

Xie, Xin ^{[1
]}

Stubbington, Michael J. T. ^{[2
]}

Nissen, Jesper K. ^{[1
]}

Andersen, Kristian G. ^{[1
]}

Hebenstreit, Daniel ^{[1
]}

Teichmann, Sarah A. ^{[2
]}

Betz, Alexander G. ^{[1
]}

机构：

[1] MRC Lab Mol Biol, Cambridge, England

[2] European Bioinformat Inst, European Mol Biol Lab, Hinxton, England

来源：

PLOS GENETICS | 2015年 / 11卷 / 06期

基金：

英国医学研究理事会; 欧洲研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

HISTONE DEACETYLASES; EPIGENETIC CHANGES; TARGET GENES; RNA-SEQ; TRANSCRIPTION; PROTEIN; TREG; INTERLEUKIN-2; ACETYLATION; ACTIVATION;

D O I：

10.1371/journal.pgen.1005251

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The lineage factor Foxp3 is essential for the development and maintenance of regulatory T cells, but little is known about the mechanisms involved. Here, we demonstrate that an N-terminal proline-rich interaction region is crucial for Foxp3's function. Subdomains within this key region link Foxp3 to several independent mechanisms of transcriptional regulation. Our study suggests that Foxp3, even in the absence of its DNA-binding forkhead domain, acts as a bridge between DNA-binding interaction partners and proteins with effector function permitting it to regulate a large number of genes. We show that, in one such mechanism, Foxp3 recruits class I histone deacetylases to the promoters of target genes, counteracting activation-induced histone acetylation and thereby suppressing their expression.

引用

页数：32

共 63 条

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