Identification of the functional molecular complexes of GATA3 in Th2 cells.

• Project/Area Number: 20790367
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Chiba University
• Principal Investigator: HOSOKAWA Hiroyuki Chiba University, 大学院・医学研究院, 助教 (60431756)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: GATA3 / Th2細胞 / クロマチン / プロテオミクス / アレルギー

Research Abstract

GATA3 is the master transcription factor for T helper 2 (Th2) cell differentiation and is critical for the expression of Th2 cytokines. Little is known, however, about the nature of the functional molecular complexes of GATA3. We identified a chromodomain-containing transcription factor, chromodomain helicase DNA binding protein 4 (Chd4) in the GATA3 complex present in Th2 cells. We found that Th2 cell differentiation is impaired in Chd4-knockdown cells and Chd4 binds to the Th2 cytokine gene loci in a GATA3-dependent manner. These results suggest that the GATA3-dependent recruitment of Chd4 at the Th2 cytokine gene loci is involved in the induction of Th2 cytokine expression.

Research Products

• [Journal Article] CD69 controls the pathogenesis of allergic airway inflammation. (2009)
  • Author(s): Miki, H.T., Hasegawa, A., Iwamura, C., Shinoda, K., Tofukuji, S., Watanabe, Y., Hosokawa, H., Motohashi, S., Hashimoto, K., Shirai, M., Yamashita, M., Nakayama, T.
  • Journal Title: J. Immunol. 183 Pages: 8203-8215
  • Peer Reviewed
• [Journal Article] Enhanced Th2 cell differentiation and allergen-induced airway inflammation in Zfp35-deficient mice. (2009)
  • Author(s): Kitajima, M., Iwamura, C., Miki, H.T., Shinoda, K., Endo, Y., Watanabe, Y., Shinnakasu, R., Hosokawa, H., Hashimoto, K., Motohashi, S., Koseki, H., Ohara, O., Yamashita, M., Nakayama, T.
  • Journal Title: J. Immunol. 183 Pages: 5388-5396
  • Peer Reviewed
• [Journal Article] cAMPQ1 activation by PACAP/VIP stimulates IL-6 release and inhibits osteoblastic differentiation through VPAC2 receptor in osteoblastic MC3T3 cells. (2009)
  • Author(s): Nagata, A., Tanaka, T., Minezawa, A., Poyurovsky, M., Mayama, T., Suzuki, S., Hashimoto, N., Yoshida, T., Suyama, K., Miyata, A., Hosokawa, H., Nakayama, T., Tatsuno, I.
  • Journal Title: J. Cell. Physiol. 221 Pages: 75-83
  • Peer Reviewed
• [Journal Article] CD69 controls the pathogenesis of allergic airway inflammation (2009)
  • Author(s): Miki, H.T.
  • Journal Title: J.Immunol. 183 Pages: 8203-8215
  • Peer Reviewed
• [Journal Article] Enhanced Th2 cell differentiation and allergen-induced airway inflammation in Zfp35-deficient mice (2009)
  • Author(s): Kitajima, M.
  • Journal Title: J.Immunol. 183 Pages: 5388-5396
  • Peer Reviewed
• [Journal Article] cAMP^<Q1> activation by PACAP/VIP stimulates IL-6 release and inhibits osteoblastic differentiation through VPAC2 receptor in osteoblastic MC3T3 cells (2009)
  • Author(s): Nagata, A.
  • Journal Title: J.Cell.Physiol. 221 Pages: 75-83
  • Peer Reviewed
• [Journal Article] Gfi1-mediated stabilization of GATA3 protein is required for Th2 cell differentiation. (2008)
  • Author(s): Shinnakasu, R., Yamashita, M., Kuwahara, M., Hosokawa, H., Hasegawa, A., Motohashi, S., Nakayama, T.
  • Journal Title: J. Biol. Chem. 283 Pages: 28216-28225
  • Peer Reviewed
• [Journal Article] Lymphoid enhancer factor interacts with GATA-3 and controls its function in T helper type 2 cells. (2008)
  • Author(s): Hossain, M.B., Hosokawa, H., Hasegawa, A., Watarai, H., Taniguchi, M., Yamashita, M., Nakayama, T.
  • Journal Title: Immunology 125 Pages: 377-386
  • Peer Reviewed
• [Journal Article] Human Th1 differentiation induced by lipoarabinomannan/lipomannan from Mycobacterium bovis BCG Tokyo -172 (2008)
  • Author(s): Ito, T., Hasegawa, A., Hosokawa, H., Yamashita, M., Motohashi, S., Naka, T., Okamoto, Y., Fujita, Y., Ishii, Y., Taniguchi, M., Yano, I., Nakayama, T.
  • Journal Title: Int. Immunol. 20 Pages: 849-860
  • Peer Reviewed
• [Journal Article] Bmi1 regulates memory CD4 T cell survival via repression of the Noxa gene. (2008)
  • Author(s): Yamashita, M., Kuwahara, M., Suzuki, A. 、, Hirahara, K., Shinnakasu, R., Hosokawa, H., Hasegawa, A., Motohashi, S., Iwama, A., Nakayama, T.
  • Journal Title: Exp. Med. 205 Pages: 1109-1120
  • Peer Reviewed
• [Journal Article] Gfil-mediated stabilization of GATA3 protein is required for Th2 cell differentiation (2008)
  • Author(s): Shinnakasu, R.
  • Journal Title: J. Biol. Chem 283 Pages: 28216-28225
  • Peer Reviewed
• [Journal Article] Lymphoid enhancer factor interacts with GATA-3 and controls its function in T helper type 2 cells (2008)
  • Author(s): Hossain, M. B.
  • Journal Title: Immunology 125 Pages: 377-386
  • Peer Reviewed
• [Journal Article] Human T_hl differentiation induced by lipoarabinomannan/lipomannan from Mycobacterium bovis BCG Tokyo-172 (2008)
  • Author(s): Ito, T.
  • Journal Title: Int. Immunol. 20 Pages: 849-860
  • Peer Reviewed
• [Journal Article] Bmil regulates memory CD4 T cell survival via repression of the Noxa gene (2008)
  • Author(s): Yamashita, M.
  • Journal Title: J. Exp. Med. 205 Pages: 1109-1120
  • Peer Reviewed
• [Presentation] Transcription factor MLL regulates IL-4 mediated anti -tumor response by tumor specific memory Th2 cells (2009)
  • Author(s): Hosokawa, H.
  • Organizer: 39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-03
• [Presentation] Transcription factor MLL regulates IL-4 mediated anti-tumor response by tumor specific memory Th2 cells (2009)
  • Author(s): Hosokawa, H
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-03
• [Presentation] Regulation of memory Th cell survival and function by the polycomb and trithorax group gene products. (2009)
  • Author(s): Nakayama, T., Hosokawa, H.
  • Organizer: The 5th International Workshop of Kyoto T Cell Conference 2009
  • Place of Presentation: 京都
  • Year and Date: 2009-06-04
• [Presentation] Regulation of memory Th cell survival and function by the polycomb and trithorax group gene products (2009)
  • Author(s): Nakayama, T.
  • Organizer: The 5th International Workshop of Kyoto T Cell Conference 2009
  • Place of Presentation: 京都
  • Year and Date: 2009-06-04
• [Presentation] Bmi1はNoxa遺伝子の発現抑制を介してメモリーTh細胞の生存を制御する/Bmi1 regulates memory CD4 T cell survival via repression of the Noxa gene. (2008)
  • Author(s): Yamashita, M., Hosokawa, H.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] Lymphoid enhancer factor 1 (LEF1)はGATA3に会合しその機能を調節する/Lymphoid enhancer factor interacts with GATA3 and controls its function in T helper type 2 cells (2008)
  • Author(s): 細川裕之
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-01
• [Presentation] BCG Tokyo-172から分離精製したLAM/LM分子によるHuman Th1分化誘導機構/Human Th1 differentiation induced by lipoarabinomannan/lipomannan from Mycobacterium bovis BCG Tokyo-172. (2008)
  • Author(s): Ito, T., Hosokawa, H.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-01
• [Presentation] Lymphoid enhancer factor 1(LEF1)はGATA3に会合しその機能を調節する/Lymphoid enhancer factor interacts with GATA3 and controls its function in T helper type 2 cells (2008)
  • Author(s): 細川裕之
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] BCG Tokyo-72から分離精製したLAM/LM分子によるHuman Th1分化誘導機構/Human Th1 differentiation induced by lipoarabinomannan/lipomannan from Mycobacterium bovis BCG Tokyo-172 (2008)
  • Author(s): Ito, T.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] BmilはNoxa遺伝子の発現抑制を介してメモリーTh細胞の生存を制御する/Bmil regulates memory CD4 T cell survival via repression of the Noxa gene (2008)
  • Author(s): Yamashita, M.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都