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

Sawako Muroi, Yoshinori Naoe, Chizuko Miyamoto, Kaori Akiyama, Tomokatsu Ikawa, Kyoko Masuda, Hiroshi Kawamoto, Ichiro Taniuchi

研究成果: Article査読

126 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1113-1121
ページ数9
ジャーナルNature Immunology
9
10
DOI
出版ステータスPublished - 2008
外部発表はい

All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学

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