Cascading suppression of transcriptional silencers by ThPOK seals helper T cell fate

被引：127

作者：

Muroi, Sawako ^{[1
,2
]}

Naoe, Yoshinori ^{[1
]}

Miyamoto, Chizuko ^{[1
]}

Akiyama, Kaori ^{[1
]}

Ikawa, Tomokatsu ^{[3
]}

Masuda, Kyoko ^{[3
]}

Kawamoto, Hiroshi ^{[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, Kawaguchi, Saitama 3320012, Japan

[3] RIKEN, Res Ctr Allergy & Immunol, Lab Lymphocyte Dev, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

来源：

NATURE IMMUNOLOGY | 2008年 / 9卷 / 10期

基金：

日本科学技术振兴机构;

关键词：

D O I：

10.1038/ni.1650

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

CD4 and the transcription factor ThPOK are essential for the differentiation of major histocompatibility complex class II restricted thymocytes into the helper T cell lineage; their genes (Cd4 and Zbtb7b (called 'ThPOK' here)) are repressed by transcriptional silencer elements in cytotoxic T cells. The molecular mechanisms regulating expression of these genes during helper T cell lineage differentiation remain unknown. Here we showed that inefficient upregulation of ThPOK, induced by removal of the proximal enhancer from the ThPOK locus, resulted in the transdifferentiation of helper lineage-specified cells into the cytotoxic T cell lineage. Furthermore, direct antagonism by ThPOK of the Cd4 and ThPOK silencers generated two regulatory loops that initially inhibited Cd4 downregulation and later stabilized ThPOK expression. Our results show how an initial lineage-specification signal can be amplified and stabilized during the lineage-commitment process.

引用

页码：1113 / 1121

页数：9

共 40 条

[31] Contingent gene regulatory networks and B cell fate specification [J].