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

Research output: Contribution to journalArticlepeer-review

112 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1113-1121
Number of pages9
JournalNature Immunology
Volume9
Issue number10
DOIs
Publication statusPublished - 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Cascading suppression of transcriptional silencers by ThPOK seals helper T cell fate'. Together they form a unique fingerprint.

Cite this