Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 2730K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yamashita, M. Articles by Nakayama, T. Search for Related Content PubMed PubMed Citation Articles by Yamashita, M. Articles by Nakayama, T. Social Bookmarking                            What's this?

¹ Department of Immunology and ² Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan

CORRESPONDENCE Toshinori Nakayama: tnakayama{at}faculty.chiba-u.jp

The maintenance of memory T cells is central to the establishment of immunological memory, although molecular details of the process are poorly understood. In the absence of the polycomb group (PcG) gene Bmi1, the number of memory CD4⁺ T helper (Th)1/Th2 cells was reduced significantly. Enhanced cell death of Bmi1^–/– memory Th2 cells was observed both in vivo and in vitro. Among various proapoptotic genes that are regulated by Bmi1, the expression of proapoptotic BH3-only protein Noxa was increased in Bmi1^–/– effector Th1/Th2 cells. The generation of memory Th2 cells was restored by the deletion of Noxa, but not by Ink4a and Arf. Direct binding of Bmi1 to the Noxa gene locus was accompanied by histone H3-K27 methylation. The recruitment of other PcG gene products and Dnmt1 to the Noxa gene was highly dependent on the expression of Bmi1. In addition, Bmi1 was required for DNA CpG methylation of the Noxa gene. Moreover, memory Th2-dependent airway inflammation was attenuated substantially in the absence of Bmi1. Thus, Bmi1 controls memory CD4⁺ Th1/Th2 cell survival and function through the direct repression of the Noxa gene.

© 2008 Yamashita et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Wang, Q., Mora-Jensen, H., Weniger, M. A., Perez-Galan, P., Wolford, C., Hai, T., Ron, D., Chen, W., Trenkle, W., Wiestner, A., Ye, Y. (2009). ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells. Proc. Natl. Acad. Sci. USA 106: 2200-2205 [Abstract] [Full Text]  
• Yamashita, M., Kuwahara, M., Suzuki, A., Hirahara, K., Shinnaksu, R., Hosokawa, H., Hasegawa, A., Motohashi, S., Iwama, A., Nakayama, T. (2008). Bmi1 regulates memory CD4 T cell survival via repression of the Noxa gene. JCB 181: i5-i5 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS