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

Ruka Setoguchi; Masashi Tachibana; Yoshinori Naoe; Sawako Muroi; Kaori Akiyama; Chieko Tezuka; Tsukasa Okuda; Ichiro Taniuchi

doi:10.1126/science.1151844

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

Science. 2008 Feb 8;319(5864):822-5. doi: 10.1126/science.1151844.

Authors

Ruka Setoguchi¹, Masashi Tachibana, Yoshinori Naoe, Sawako Muroi, Kaori Akiyama, Chieko Tezuka, Tsukasa Okuda, Ichiro Taniuchi

Affiliation

¹ Laboratory for Transcriptional Regulation, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.

PMID: 18258917
DOI: 10.1126/science.1151844

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Cell Lineage
Chromatin Immunoprecipitation
Core Binding Factor Alpha 2 Subunit / genetics
Core Binding Factor Alpha 2 Subunit / physiology*
Core Binding Factor Alpha 3 Subunit / genetics
Core Binding Factor Alpha 3 Subunit / physiology*
Core Binding Factor beta Subunit / metabolism
Histocompatibility Antigens Class I / immunology
Histocompatibility Antigens Class II / immunology
Mice
Mice, Transgenic
Molecular Sequence Data
Silencer Elements, Transcriptional
T-Lymphocyte Subsets / cytology
T-Lymphocyte Subsets / immunology*
T-Lymphocyte Subsets / metabolism
T-Lymphocytes, Cytotoxic / cytology
T-Lymphocytes, Cytotoxic / immunology*
T-Lymphocytes, Cytotoxic / metabolism
T-Lymphocytes, Helper-Inducer / cytology
T-Lymphocytes, Helper-Inducer / immunology
T-Lymphocytes, Helper-Inducer / metabolism
Transcription Factors / genetics
Transcription Factors / physiology*

Substances

Cbfb protein, mouse
Core Binding Factor Alpha 2 Subunit
Core Binding Factor Alpha 3 Subunit
Core Binding Factor beta Subunit
Histocompatibility Antigens Class I
Histocompatibility Antigens Class II
Runx1 protein, mouse
Runx3 protein, mouse
Th-POK protein, mouse
Transcription Factors

Associated data

GENBANK/EU371956