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Science 319 (5864): 822-825

Copyright © 2008 by the American Association for the Advancement of Science

Repression of the Transcription Factor Th-POK by Runx Complexes in Cytotoxic T Cell Development

Ruka Setoguchi,1*{dagger} Masashi Tachibana,1* Yoshinori Naoe,1* Sawako Muroi,1,2 Kaori Akiyama,1,2 Chieko Tezuka,1 Tsukasa Okuda,3 Ichiro Taniuchi1,2{ddagger}

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.

1 Laboratory for Transcriptional Regulation, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
2 Precursory Research for Embryonic Science and Techonology (PRESTO), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
3 Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.

* These authors contributed equally to this work.

{dagger} Present address: Department of Immunology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195–7650, USA.

{ddagger} To whom correspondence should be addressed. E-mail: taniuchi{at}rcai.riken.jp


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