Polycomb and Trithorax complexes control epigenetic memory of T helper cells

• Project/Area Number: 25860351
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Chiba University
• Principal Investigator: ONODERA Atsushi 千葉大学, 医学(系)研究科(研究院), 助教 (10586598)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 免疫記憶 / 発生・分化 / エピジェネティクス / アレルギー・ぜんそく / 発現制御

Outline of Final Research Achievements

One-thirds of Japanese suffer from allergies, which are caused by imbalances in the immune system. We focus on helper T (Th) cells because they are thought to play important roles both in development of the allergic diseases and host defense against pathogens. Polycomb and Trithorax proteins regulate Th cell function via binding to specific genes, and we propose that their spatial interplay is crucial for regulating target gene transcription. In this study, we investigated the roles of Ezh2, one of the Polycomb group proteins, and demonstrated that it functions to prevent unwanted immune responses. We also clarified the roles of Menin, one of the Trithorax group proteins, in the pathogenesis of steroid-resistant asthma. We hope that these findings will be applied to the development of therapies for allergic disease.

Research Products

• [Journal Article] Epigenetics of T cells regulated by Polycomb/Trithorax molecules. (2015)
  • Author(s): Onodera, A., and Nakayama, T.
  • Journal Title: Trends Mol. Med. Volume: - Issue: 5 Pages: 1-11
  • DOI: 10.1016/j.molmed.2015.03.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Trithorax complex component Menin controls differentiation and maintenance of T helper 17 cells. (2014)
  • Author(s): Watanabe, Y., Onodera, A., Kanai, U., Ichikawa, T., Obata-Ninomiya, K., Wada, T., Kiuchi, M., Iwamura, C., Tumes, DJ., Shinoda, K., Yagi, R., Motohashi, S., Hirahara, K. and Nakayama, T.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 111(35) Issue: 35 Pages: 12829-34
  • DOI: 10.1073/pnas.1321245111
  • Peer Reviewed / Open Access
• [Journal Article] Sox5 and c-Maf cooperatively induce Th17 cell differentiation via ROR gamma t induction as downstream targets of Stat3 (2014)
  • Author(s): Tanaka S, Suto A, Iwamoto T, Kashiwakuma D, Kagami S, Suzuki K, Takatori H, Tamachi T, Hirose K, Onodera A, Suzuki J, Ohara O, Yamashita M, Nakayama T, Nakajima H
  • Journal Title: J Exp Med Volume: 211 Issue: 9 Pages: 1857-1874
  • DOI: 10.1084/jem.20130791
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Histone acetylation mediated by Brd1 is crucial for Cd8 gene activation during early thymocyte development. (2014)
  • Author(s): Mishima Y, Wang C, Miyagi S, Saraya A, Hosokawa H, Mochizuki-Kashio M, Nakajima-Takagi Y, Koide S, Negishi M, Sashida G, Naito T, Ishikura T, Onodera A, Nakayama T, Tenen DG, Yamaguchi N, Koseki H, Taniuchi I, Iwama A.
  • Journal Title: Nature Communications Volume: 18 Issue: 1 Pages: 5872-5882
  • DOI: 10.1038/ncomms6872
  • Peer Reviewed / Open Access
• [Journal Article] The polycomb protein Ezh2 regulates differentiation and plasticity of CD4+ T helper type-1 and type-2 cells. (2013)
  • Author(s): Tumes, D. J., Onodera, A., Suzuki, A., Shinoda, K., Endo, Y., Iwamura, C., Hosokawa, H., Koseki, H., Tokoyoda, K., Suzuki, Y., Motohashi, S., and Nakayama, T.
  • Journal Title: Immunity Volume: 39 Issue: 5 Pages: 819-32
  • DOI: 10.1016/j.immuni.2013.09.012
  • Peer Reviewed
• [Journal Article] Genomic-wide gene expression profiling revealed a critical role for GATA3 in the maintenance of the Th2 cell identity. (2013)
  • Author(s): Sasaki, T., Onodera, A., Hosokawa, H., Watanabe, Y., Horiuchi, S., Yamashita, J., Tanaka, H., Ogawa, Y., Suzuki, Y., and Nakayama, T.
  • Journal Title: PLOS ONE Volume: 8 Issue: 6 Pages: e66468-e66468
  • DOI: 10.1371/journal.pone.0066468
  • Peer Reviewed
• [Presentation] Polycomb and Trithorax complexes control epigenetic memory of T helper cells. (2015)
  • Author(s): Onodera, A. and Nakayama, T.
  • Organizer: International Symposium on Genome Science 2015
  • Place of Presentation: 一橋講堂、東京都、千代田区
  • Year and Date: 2015-01-20 – 2015-01-21
• [Presentation] Polycomb and Trithorax complexes control epigenetic memory of T helper cells. (2014)
  • Author(s): Onodera, A., and Nakayama, T.
  • Organizer: 第43回日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館、京都府、京都市
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Sox5 and c-Maf cooperatively induce Th17 cell differentiation via RORgt induction as downstream targets of Stat3. (2014)
  • Author(s): Tanaka, S., Suto, A., Iwamoto, T., Suzuki, K., Takatori, H., Tamachi, T., Hirose, K., Onodera, A., Suzuki, J., Ohara, O., Yamashita, M., Nakayama, T., and Nakajima, H.
  • Organizer: 第43回日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館、京都府、京都市
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] The trithorax complex component Menin controls differentiation and maintenance of T helper 17 cells. (2014)
  • Author(s): Watanabe, Y., Onodera, A., Ichikawa, T., Obata-Ninomiya, K., Wada, T., Kiuchi, M., Morimoto, Y., Shinoda, K., Yagi, R., Motohashi, S., Hirahara, K., and Nakayama, T.
  • Organizer: 第43回日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館、京都府、京都市
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] The polycomb protein Ezh2 regulates differentiation and plasticity of CD4 T helper type-1 and type-2 cells. (2014)
  • Author(s): Tumes, J. D., Onodera, A., Hosokawa, H., Koseki, H., Suzuki, Y., Motohashi, S., and Nakayama, T.
  • Organizer: 第24回Kyoto T cell Conference
  • Place of Presentation: 京都平安ホテル、京都府、京都市
  • Year and Date: 2014-05-16 – 2014-05-17
• [Presentation] Cellular memory of T helper type 2 cells controlled by GATA3 and epigenetic regulators.
  • Author(s): Onodera, A., Horiuchi, S., Sasaki, T., Hosokawa, H., Watanabe, Y., and Nakayama, T.
  • Organizer: 第42回日本免疫学会総会学術集会
  • Place of Presentation: 幕張メッセ (千葉県千葉市)
• [Presentation] Generation and maintenance of pathogenic memory CD4 T cells.
  • Author(s): Nakayama, T., Endo, Y., Onodera, A., and Tumes, D. J.
  • Organizer: The 3rd CSI/JSI/KAI Joint Symposium on Immunology
  • Place of Presentation: POSTECH Biotech Center(慶尚北道浦項市･韓国)
• [Presentation] The histone methyltransferase Ezh2 regulates differentiation and plasticity of CD4 T helper cells.
  • Author(s): Tumes, D., Onodera, A., Suzuki, A., Shinoda, K., Endo, Y., Iwamura, C., Hosokawa, H., Koseki, H., Tokoyoda, K., Suzuki, Y., and Nakayama, T.
  • Organizer: AAI Annual Meeting
  • Place of Presentation: Hawaii Convention Center (Honolulu, Hawaii)
• [Book] Transcriptional and Epigenetic Mechanisms Regulating Normal and Aberrant Blood Cell Development (2014)
  • Author(s): Onodera, A., Tumes, D. J., and Nakayama, T.
  • Total Pages: 416
  • Publisher: Springer Berlin Heidelberg
• [Remarks] 千葉大学大学院医学研究院免疫発生学
  • URL: http://www.m.chiba-u.ac.jp/class/meneki/
• [Remarks] 国立大学法人 千葉大学ホームページ
  • URL: http://www.chiba-u.ac.jp/general/publicity/press/pdf/2013/20131111.pdf
• [Remarks] 独立行政法人 科学技術振興機構(JST)ホームページ
  • URL: http://www.jst.go.jp/pr/announce/20131115/