Molecular basis of Polycomb and Trithorax complexes in the maintenance of immunological memory

• Project/Area Number: 23790523
• 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, 大学院・医学研究院, 助教 (10586598)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• 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 / アレルギー･ぜんそく

Research Abstract

Allergic disease, which is caused by a disorder of the balance of the immune system, is said to be the Japanese national disease. We focus on Th2 cells because they are thought to play leading role in development of the allergic disease. Polycomb and Trithorax proteins regulate Th2 cell function via binding to specific genes. We made gene maps of the place where they bound using an advanced technique called the ChIP-seq method and discovered some unexpected characteristics. In addition, we found that allergic reactions were attenuated in the mice lacking the Trithorax molecules. We hope that these findings will be applied to the development of therapies for allergic disease.

Research Products

• [Journal Article] Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity. (2013)
  • Author(s): Hosokawa H
  • Journal Title: Proc Natl Acad Sci U SA Volume: - Issue: 12 Pages: 4691-4696
  • DOI: 10.1073/pnas.1220865110
  • Peer Reviewed
• [Journal Article] Too much of a good thing. (2013)
  • Author(s): Onodera, A., Tumes, D. J., and Nakayama, T.
  • Journal Title: Nat. Immunol. Volume: 14 Issue: 2 Pages: 112-114
  • DOI: 10.1038/ni.2510
• [Journal Article] Th2特異的遺伝子のGATA3依存的 (2013)
  • Author(s): 堀内周、小野寺淳、中山俊憲
  • Journal Title: 非依存的な発現制御機構臨床免疫・アレルギー科(科学評論社) Volume: 59(1) Pages: 25-33
• [Journal Article] Th2特異的遺伝子のGATA3依存的，非依存的な発現制御機構 (2013)
  • Author(s): 堀内周、小野寺淳、中山俊憲
  • Journal Title: 臨床免疫・アレルギー科 Volume: 59 Pages: 25-33
• [Journal Article] The transcription factor Sox4 is a downstream target of signaling by the cytokine TGF-・ and suppresses TH2 differentiation (2012)
  • Author(s): Kuwahara, M., Yamashita, M., Shinoda, K., Tofukuji, S., Onodera, A., Shinnakasu, R., Motohashi, S., Hosokawa, H., Tumes, D., Iwamura, C., Lefebvre, V., and Nakayama, T.
  • Journal Title: Nat. Immunol Volume: 13(8) Issue: 8 Pages: 778-786
  • DOI: 10.1038/ni.2362
  • Peer Reviewed
• [Journal Article] 中山俊憲STAT6依存的および非依存的なGata3の発現制御機構-Gata3発現はSTAT6によって誘導され (2012)
  • Author(s): 小野寺淳
  • Journal Title: Menin/TrxG複合体によって維持される-臨床免疫・アレルギ-科 Volume: 57(3) Pages: 330-341
• [Journal Article] 中山俊憲CD4免疫記憶と機能維持-エピジェネティック研究から得られた新知見 (2011)
  • Author(s): 小野寺淳、堀内周
  • Journal Title: 実験医学増刊免疫学のブラックボックス免疫記憶の制御と疾患治療 Volume: 29(17) Pages: 20-28
• [Journal Article] Memory type 2 helper T cells induce long-lasting anti-tumor immunityby activating natural killer cells (2011)
  • Author(s): Kitajima, M., Ito, T., Tumes, J. D., Endo, Y., Onodera, A., Hashimoto, K., Motohashi, S., Yamashita, M., Nishimura, T., Ziegler, F. S. Nakayama, T
  • Journal Title: Cancer Res Volume: 71 Issue: 14 Pages: 4790-4798
  • DOI: 10.1158/0008-5472.can-10-1572
  • Peer Reviewed
• [Journal Article] T細胞機能分化のエピジェネティクス (2011)
  • Author(s): 小野寺淳、中山俊憲
  • Journal Title: 感染・炎症・免疫 Volume: 41(2) Pages: 22-31
• [Journal Article] Genome-wide analysis reveals unique regulation of transcription of Th2-specific genes by GATA3 (2011)
  • Author(s): Horiuchi, S., Onodera, A., Hosokawa, H., Watanabe, Y., Tanaka, T., Sugano, S., SuzukiY. Nakayama, T
  • Journal Title: J. Immunol Volume: 186 Issue: 11 Pages: 6378-6389
  • DOI: 10.4049/jimmunol.1100179
  • Peer Reviewed
• [Journal Article] ポリコームとトライソラックスによるGata3遺伝子発現のエピジェネティック制御 (2011)
  • Author(s): 小野寺淳
  • Journal Title: 医学のあゆみ Volume: 237(13) Pages: 1154-1160
• [Journal Article] Gata3遺伝子のエピジェネティック制御 (2011)
  • Author(s): 小野寺淳
  • Journal Title: 医学のあゆみ Volume: 237(4) Pages: 314-314
• [Journal Article] Memory type 2 helper T cells induce long-lasting anti-tumor immunity by activating natural killer cells. 71:4790-4798 (2011). (2011)
  • Author(s): Kitajima, M., Ito, T., Tumes, J. D., Endo, Y., Onodera, A., Hashimoto, K., Motohashi, S., Yamashita, M., Nishimura, T., Ziegler, F. S. and Nakayama, T.
  • Journal Title: Cancer Res. Volume: 71 Pages: 4790-4798
  • Peer Reviewed
• [Presentation] Epigenetic regulation of helper T cells by Polycomb and Trithorax complexes (2013)
  • Author(s): Onodera, A., Horiuchi, S., Sasaki, T., Hosokawa, H., Watanabe, Y., Suzuki, Y., and Nakayama, T.
  • Organizer: International Symposium on Genome Science
  • Place of Presentation: Tokyo
  • Year and Date: 2013-01-09
• [Presentation] Regulation of memory CD4 T cell pool size and function by NKT cells invivo (2012)
  • Author(s): Iwamura, C., Endo, Y., Onodera, A.,Watanabe, Y., Suzuki, A., Kinjo, Y., and Nakayama, T.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-06
• [Presentation] Genome-wide gene expression profiling revealed a critical role for GATA3 in the maintenance of the Th2 cell phenotype (2012)
  • Author(s): Sasaki, T., Onodera, A., Hosokawa, H., Watanabe, Y., Horiuchi, S., Yamashita, J., and Nakayama, T.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-05
• [Presentation] メモリ-Th2 細胞は NK 細胞を活性化し抗腫瘍効果を持続させる/ Memory type2 helper T cells induce long-lasting anti-tumor immunity by activating natural killer cells (2011)
  • Author(s): Ito, T., Kitajima, M., Tumes, J. D., Endo, Y., Onodera, A., Hashimoto, K., Motohashi, S., Yamashita, M., Nishimura, T., and Nakayama,T.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
  • Year and Date: 2011-11-28
• [Presentation] STAT6 によって誘導されるポリコームとトライソラックスの置換反応/STAT6-mediated displacement of Polycomb by Trithorax complex establishes long-term maintenance of GATA3 expression in Th2 cells (2011)
  • Author(s): Onodera, A., Yamashita, M., Endo, Y., Kuwahara, M., Tofukuji, S., Hosokawa, H., Horiuchi, S., Watanabe, Y., and Nakayama,T.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
  • Year and Date: 2011-11-27
• [Presentation] GATA3 ChIP-sequence 解析を用いたTh2特異的遺伝子の転写調節機構の解明/Genome-wide analysis revealsunique regulation of transcription of Th2-specific genes by GATA3 (2011)
  • Author(s): 堀内周、小野寺淳、細川裕之、渡邊友紀子、中山俊憲
  • Organizer: 第40回日 本免疫学会学術集会
  • Place of Presentation: 幕張
  • Year and Date: 2011-11-27
• [Presentation] Genome-wide analysis reveals unique regulation of transcription of Th2-specific genes by GATA3 (2011)
  • Author(s): Onodera, A., Horiuchi, S., Hosokawa, H., Watanabe, Y., Suzuki, Y., and Nakayama, T.
  • Organizer: NCI Symposium on Chromosome Structure and Function
  • Place of Presentation: Bethesda, MD, USA
  • Year and Date: 2011-11-01
• [Presentation] Regulation of memory Th2 cell function and allergic airway inflammation via polycomb and trithorax molecules (2011)
  • Author(s): Nakayama, T., and Onodera, A.
  • Organizer: 30^<th> Congress of the European Academy of Allergy and Clinical Immunology
  • Place of Presentation: Istanbul, Turkey
  • Year and Date: 2011-06-15
• [Presentation] Eomesodermin controls IL-5 production inmemory Th2 cells through the inhibition of GATA3 activity (2011)
  • Author(s): 遠藤裕介、小野寺淳、細川裕之、中山俊憲
  • Organizer: 第21回Kyoto T Cell Conference
  • Place of Presentation: 京都
  • Year and Date: 2011-06-11
• [Presentation] Epigenetic control of memory Th2 cell function via Polycomb and Trithorax molecules (2011)
  • Author(s): Nakayama,T.,and Onodera, A.
  • Organizer: EUThyme-Rolduc Meeting
  • Place of Presentation: Leeuwenhorst, NL
  • Year and Date: 2011-05-24
• [Presentation] GATA3 ChIP-sequence解析を用いたTh2特異的遺伝子の転写調節機構の解明 (2011)
  • Author(s): 堀内周、小野寺淳、細川裕之、渡邊友紀子、鈴木穣、中山俊憲
  • Organizer: 第5回日本エピジェネティックス研究会
  • Place of Presentation: 熊本
  • Year and Date: 2011-05-19
• [Presentation] Epigenetic control of memory Th2 cell function via Polycomb and Trithorax molecules. (2011)
  • Author(s): Nakayama, T., and Onodera, A.
  • Organizer: EUThyme-Rolduc Meeting
  • Place of Presentation: Leeuwenhorst, NL
• [Presentation] Regulation of memory Th2 cell function and allergic airway inflammation via polycomb and trithorax molecules. (2011)
  • Author(s): Nakayama, T., and Onodera, A.
  • Organizer: 30th Congress of the European Academy of Allergy and Clinical Immunology
  • Place of Presentation: Istanbul, Turkey
• [Presentation] Eomesodermin controls IL-5 production in memory Th2 cells through the inhibition of GATA3 activity (2011)
  • Author(s): 遠藤裕介、小野寺淳、細川裕之、中山俊憲.
  • Organizer: 第21回Kyoto T Cell Conference
  • Place of Presentation: 京都
• [Presentation] Genome-wide analysis reveals unique regulation of transcription of Th2-specific genes by GATA3. (2011)
  • Author(s): Onodera, A., Horiuchi, S., Hosokawa, H., Watanabe, Y., Suzuki, Y., and Nakayama, T..
  • Organizer: NCI Symposium on Chromosome Structure and Function
  • Place of Presentation: Bethesda, MD, USA
• [Presentation] GATA3 ChIP-sequence解析を用いたTh2特異的遺伝子の転写調節機の解明/ Genome-wide analysis reveals unique regulation of transcription of Th2-specific genes by GATA3. (2011)
  • Author(s): 堀内周、小野寺淳、細川裕之、渡邊友紀子、中山俊憲
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
• [Presentation] STAT6によって誘導されるポリコ－ムとトライソラックスの置換反応/ STAT6-mediated displacement of Polycomb by Trithorax complex establishes long-term maintenance of GATA3 expression in Th2 cells. (2011)
  • Author(s): Onodera, A., Yamashita, M., Endo, Y., Kuwahara, M., Tofukuji, S., Hosokawa, H., Horiuchi, S., Watanabe, Y., and Nakayama, T
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
• [Presentation] メモリ－Th2細胞はNK細胞を活性化し抗腫瘍効果を持続させる/ Memory type 2 helper T cells induce long-lasting anti-tumor immunity by activating natural killer cells. (2011)
  • Author(s): Ito, T., Kitajima, M., Tumes, J. D., Endo, Y., Onodera, A., Hashimoto, K., Motohashi, S., Yamashita, M., Nishimura, T., and Nakayama, T.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
• [Presentation] Epigenetic regulation of helper T cells by Polycomb and Trithorax complexes.
  • Author(s): Onodera, A., Horiuchi, S., Sasaki, T., Hosokawa, H., Watanabe, Y., Suzuki, Y., and Nakayama, T.
  • Organizer: International Symposium on Genome Science
  • Place of Presentation: 東京
• [Presentation] Regulation of memory CD4 T cell pool size and function by NKT cells in vivo.
  • Author(s): Iwamura, C., Endo, Y., Onodera, A., Watanabe, Y., Suzuki, A., Kinjo, Y., and Nakayama, T.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
• [Presentation] Genome-wide gene expression profiling revealed a critical role for GATA3 in the maintenance of the Th2 cell phenotype.
  • Author(s): Sasaki, T., Onodera, A., Hosokawa, H., Watanabe, Y., Horiuchi, S., Yamashita, J., and Nakayama, T.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸