Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 8 February 2008:
Vol. 319. no. 5864, pp. 822 - 825
DOI: 10.1126/science.1151844
Prev | Table of Contents | Next

Reports

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}

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

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus.
M. Zamisch, L. Tian, R. Grenningloh, Y. Xiong, K. F. Wildt, M. Ehlers, I-C. Ho, and R. Bosselut (2009)
J. Exp. Med. 206, 2685-2699
   Abstract »    Full Text »    PDF »
Runx proteins regulate Foxp3 expression.
L. Bruno, L. Mazzarella, M. Hoogenkamp, A. Hertweck, B. S. Cobb, S. Sauer, S. Hadjur, M. Leleu, Y. Naoe, J. C. Telfer, et al. (2009)
J. Exp. Med. 206, 2329-2337
   Abstract »    Full Text »    PDF »
ThPOK Derepression Is Required for Robust CD8 T cell Responses to Viral Infection.
R. Setoguchi, I. Taniuchi, and M. J. Bevan (2009)
J. Immunol. 183, 4467-4474
   Abstract »    Full Text »    PDF »
CD4-CD8 Lineage Differentiation: Thpok-ing into the Nucleus.
L. Wang and R. Bosselut (2009)
J. Immunol. 183, 2903-2910
   Abstract »    Full Text »    PDF »
Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs.
F. Cruz-Guilloty, M. E. Pipkin, I. M. Djuretic, D. Levanon, J. Lotem, M. G. Lichtenheld, Y. Groner, and A. Rao (2009)
J. Exp. Med. 206, 51-59
   Abstract »    Full Text »    PDF »
The leukemogenic t(8;21) fusion protein AML1-ETO controls rRNA genes and associates with nucleolar-organizing regions at mitotic chromosomes.
R. Bakshi, S. K. Zaidi, S. Pande, M. Q. Hassan, D. W. Young, M. Montecino, J. B. Lian, A. J. van Wijnen, J. L. Stein, and G. S. Stein (2008)
J. Cell Sci. 121, 3981-3990
   Abstract »    Full Text »    PDF »
Discriminating gene expression profiles of memory B cell subpopulations.
G. R.A. Ehrhardt, A. Hijikata, H. Kitamura, O. Ohara, J.-Y. Wang, and M. D. Cooper (2008)
J. Exp. Med. 205, 1807-1817
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)