Regulatory mechanisms of allelic exclusion by epigenetics and chromosome dynamics

• Project/Area Number: 20590298
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: AGATA Yasutoshi Kyoto University, 医学研究科, 准教授 (60263141)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: エピジェネティクス / クロマチン / 対立遺伝子排除 / 転写因子 / 遺伝子発現 / エピジェネテクス / 染色体ダイナミクス / 遺伝子再構成

Research Abstract

The E2A transcription factor binds directly to genetic regions in the TCRβ locus and induces rearrangement by increasing histone acetylation. We analyzed the contraction and decontraction status of the TCRβ locus by 3D-FISH and found that V and DJ regions come into the close proximity during the stage in which rearrangement normally occurs, but become separated away from each other during the stage in which further rearrangement is inhibited. We also found that E2A overexpression induces localization of the V and DJ regions into the close proximity even in the stage in which further rearrangement is inhibited, and finally induces the rearrangement. These results suggest that E2A has the ability of inducing rearrangement not only by epigenetic changes but also by chromosome dynamics including locus contraction.

Research Products

• [Journal Article] Regulation of TCR Vγ2 gene rearrangement by the helix-loop-helix protein, E2A. (2011)
  • Author(s): Nozaki M, Wakae K, Tamaki N, Sakamoto S, Ohnishi K, Uejima T, Minato N, Yanagihara I, Agata Y.
  • Journal Title: Int Immunol. Volume: (In press)
  • Peer Reviewed
• [Journal Article] Claudin-4 induction by E-protein activity in later stages of CD4/8double-positive thymocytes to increase positive selection efficiency. (2011)
  • Author(s): Kawai Y, Hamazaki Y, Fujita H, Fujita A, Sato T, Furuse M, Fujimoto T, Jetten AM, Agata Y, Minato N.
  • Journal Title: Proc Natl Acad Sci USA. Volume: 108 Pages: 4075-4080
  • Peer Reviewed
• [Journal Article] The NF90-NF45 complex functions as a negative regulator in the microRNA processing pathway. (2009)
  • Author(s): Sakamoto S, Aoki K, Higuchi T, Todaka H, Morisawa K, Tamaki N, Hatano E, Fukushima A, Taniguchi T, Agata Y.
  • Journal Title: Mol.Cell.Biol. 29 Pages: 3754-3769
  • NAID: 120001756537
  • Peer Reviewed
• [Journal Article] 転写因子E2AとTCRβ遺伝子の対立遺伝子排除 (2009)
  • Author(s): 縣保年
  • Journal Title: 医学のあゆみ 228(11) Pages: 1126-1127
• [Journal Article] The NF90-NF45 complex functions as a negative regulator in the microRNA processing pathway. (2009)
  • Author(s): Sakamoto S, Aoki K, Higuchi T, Todaka H, Morisawa K, Tamaki N, Hatano E, Fukushima A, Taniguchi T, Agata Y.
  • Journal Title: Mol Cell Biol 29 Pages: 3754-3769
  • NAID: 120001756537
  • Peer Reviewed
• [Journal Article] 転写因子E2AとTCRβ遺伝子の対立遺伝子排除 (2009)
  • Author(s): 縣保年
  • Journal Title: 医学のあゆみ 228 Pages: 1126-1127
• [Journal Article] Regulation of histone H4 acetylation by transcription factor E2A in Ig gene conversion. (2008)
  • Author(s): Kitao, H., Kimura, M., Yamamoto, K., Seo, H., Namikoshi, K., Agata, Y., Ohta, K., Takata, M.
  • Journal Title: Int.Immunol. 20 Pages: 277-284
  • NAID: 10021239538
  • Peer Reviewed
• [Journal Article] E2AはT細胞抗原受容体遺伝子の再構成と対立遺伝子排除を制御する (2008)
  • Author(s): 縣保年
  • Journal Title: 細胞工学 27(3) Pages: 258-259
• [Presentation] E2A negatively regulates TCR Vγ3 rearrangement via transcriptional repressor, Gfi-1. (2010)
  • Author(s): 若江亨祥
  • Organizer: 第14回国際免疫学会
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-26
• [Presentation] Regulation of Vγ2 gene rearrangement by the helix-loop-helix protein, E2A. (2010)
  • Author(s): 野崎昌俊
  • Organizer: 第14回国際免疫学会
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-26
• [Presentation] Regulation of Vγ2 gene rearrangement by the helix-loop-helixprotein, E2A. (2010)
  • Author(s): Nozaki M, Tamaki N, Sakamoto S, Yanagihara I, Agata Y
  • Organizer: 14^<th>International Congress of Immunology
  • Place of Presentation: 神戸市、日本
  • Year and Date: 2010-08-26
• [Presentation] E2A negatively regulates TCR Vγ3 rearrangement via transcriptional repressor, Gfi-1. (2010)
  • Author(s): Wakae K, Yamashita M, Nakayama T, Minato N, Agata Y
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸市、日本
  • Year and Date: 2010-08-26
• [Presentation] bHLH転写因子E2AによるVγ2遺伝子再構成の制御機構 (2010)
  • Author(s): 野崎昌俊
  • Organizer: 第18回Kyoto T Cell Conference
  • Place of Presentation: 京都
  • Year and Date: 2010-06-04
• [Presentation] bHLH転写因子E2AによるVγ2遺伝子再構成の制御機構 (2010)
  • Author(s): 野崎昌俊、柳原格、懸保年
  • Organizer: Kyoto T Cell Conference
  • Place of Presentation: 京都市、日本
  • Year and Date: 2010-06-04
• [Presentation] E2A and CBP/p300 act in synergy to promote chromatin accessibility of the immunoglobulin κlocus in nonlymphoid cells. (2010)
  • Author(s): 縣保年
  • Organizer: Gene Expression & Signaling in the Immune System
  • Place of Presentation: Cold Spring Harbor, USA
  • Year and Date: 2010-04-22
• [Presentation] E2A and CBP/p300 act in synergy to promote chromatin accessibility of the immunoglobulin κ locus in nonlymphoid cells. (2010)
  • Author(s): Agata Y
  • Organizer: Gene Expression & Signaling in the Immune System
  • Place of Presentation: Cold Spring Harbor, USA
  • Year and Date: 2010-04-22
• [Presentation] Regulation of Allelic Exclusion at the TCRβLocus by the Helix-Loop-Helix Protein, E47 (2009)
  • Author(s): 縣保年
  • Organizer: Transcriptional Mechanisms of Early Lymphocyte Development
  • Place of Presentation: La Jolla, USA
  • Year and Date: 2009-11-05
• [Presentation] Regulation of Allelic Exclusion at the TCRβ Locus by the Helix-Loop-Helix Protein, E47. (2009)
  • Author(s): Agata Y, Sakamoto S, Tamaki N, Ikawa T, Masuda K, Kawamoto H, Murre C.
  • Organizer: Transcriptional Mechanisms of Early Lymphocyte Development.
  • Place of Presentation: La Jolla, USA
• [Presentation] Regulation of Allelic Exclusion at the TCRβLocus by the Helix-Loop-Helix Protein, E47 (2008)
  • Author(s): 縣保年
  • Organizer: Gene Expression & Signaling in the Immune System
  • Place of Presentation: Cold Spring Harbor, USA
  • Year and Date: 2008-04-02
• [Remarks] ホームページ等
  • URL: http://www.imm.med.kyoto-u.ac.jp/index.html