Repression of the transcription factor Th-POK by Runx complexes in cytotoxic T cell development

被引：190

作者：

Setoguchi, Ruka ^{[1
]}

Tachibana, Masashi ^{[1
]}

Naoe, Yoshinori ^{[1
]}

Muroi, Sawako ^{[1
,2
]}

Akiyama, Kaori ^{[1
,2
]}

Tezuka, Chieko ^{[1
]}

Okuda, Tsukasa ^{[3
]}

Taniuchi, Ichiro ^{[1
,2
]}

机构：

[1] RIKEN, Res Ctr Allergy & Immunol, Lab Transcript Regulat, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[2] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol PRESTO, Kawaguchi, Saitama 3320012, Japan

[3] Kyoto Prefectural Univ Med, Kamigyo Ku, Kyoto 6028566, Japan

来源：

SCIENCE | 2008年 / 319卷 / 5864期

关键词：

D O I：

10.1126/science.1151844

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：

Mouse CD4(+) CD8(+) double- positive ( DP) thymocytes differentiate into CD4(+) helper- lineage cells upon expression of the transcription factor Th- POK but commit to the CD8(+) cytotoxic lineage in its absence. We report the redirected differentiation of class I - restricted thymocytes into CD4(+) CD8(-) helper- like T cells upon loss of Runx transcription factor complexes. A Runx- binding sequence within the Th- POK locus acts as a transcriptional silencer that is essential for Th- POK repression and for development of CD8(+) T cells. Thus, Th- POK expression and genetic programming for T helper cell development are actively inhibited by Runx- dependent silencer activity, allowing for cytotoxic T cell differentiation. Identification of the transcription factors network in CD4 and CD8 lineage choice provides insight into how distinct T cell subsets are developed for regulating the adaptive immune system.

引用

页码：822 / 825

页数：4

共 21 条

[1] Groucho-dependent and -independent repression activities of runt domain proteins [J].