Purification of the functional transcription factor complex and analyses of the factors that constitute the complex

• Project/Area Number: 26670136
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Agata Yasutoshi 滋賀医科大学, 医学部, 教授 (60263141)
• Co-Investigator(Renkei-kenkyūsha): TANAKA HIROYUKI 滋賀医科大学, 医学部, 助教 (10293820) ; WAGATSUMA KEISUKE 滋賀医科大学, 医学部, 助教 (10725071)
• Research Collaborator: ANZAI YUKI
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: E2A / 転写因子 / 核内構造体 / 染色体高次構造 / 染色体ルーピング / 転写因子ファクトリー / 3D-FISH / Immuno-FISH / 転写因子foci / 3D-DNA FISH / 3C assay / 転写因子 foci / Id3

Outline of Final Research Achievements

E2A transcription factor was found to form nuclear dot-like structures called E2A foci, we thus postulated that E2A induces TCRβ gene rearrangement by chromosome looping. To elucidate the molecular mechanism underlying E2A foci formation, we identified factors that constitute the functional E2A transcription factor complex. Among them, histone acetyltransferases CBP/p300 were found to colocalze with E2A foci and to be required for E2A foci formation. Knockdown of E2A or CBP/p300 leads to abrogation of chromosome looping. These results indicate that E2A foci formation is dependent on CBP/p300 and E2A or CBP/p300 are essential for chromosome looping.

Research Products

• [Journal Article] Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program. (2016)
  • Author(s): Ikawa T, Masuda K, Endo TA, Endo M, Isono K, Koseki Y, Nakagawa R, Kometani K, Takano J, Agata Y, Katsura Y, Kurosaki T, Vidal M, Koseki H, Kawamoto H.
  • Journal Title: Genes. Dev. Volume: 30 Issue: 22 Pages: 2475-2485
  • DOI: 10.1101/gad.290593.116
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The Effect of D-Aspartate on Spermatogenesis in Mouse Testis. (2016)
  • Author(s): Tomita K, Tanaka H, Kageyama S, Nagasawa M, Wada A, Murai R, Kobayashi K, Hanada E, Agata Y, Kawauchi A
  • Journal Title: Biol Reprod. Volume: 30 Issue: 2 Pages: 1-7
  • DOI: 10.1095/biolreprod.115.134692
  • Peer Reviewed
• [Journal Article] Induced Developmental Arrest of Early Hematopoietic Progenitors Leads to the Generation of Leukocyte Stem Cells. (2015)
  • Author(s): Ikawa T, Masuda K, Huijskens M.J.A.J., Satoh R, Kakugawa K, Agata Y, Miyai T, Germeraad W.T.V., Katsura Y, Kawamoto H.
  • Journal Title: Stem Cell Reports Volume: 5 Issue: 5 Pages: 716-727
  • DOI: 10.1016/j.stemcr.2015.09.012
  • NAID: 120005745636
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The E-Id protein axis modulates the activities of the PI3K-AKT-mTORC1-Hif1a and c-myc/p19Arf pathways to suppress innate variant TFH cell development, thymocyte expansion, and lymphomagenesis. (2015)
  • Author(s): Miyazaki M, Miyazaki K, Chen S, Chandra V, Wagatsuma K, Agata Y, Rodewald HR, Saito R, Chang AN, Varki N, Kawamoto H, Murre C.
  • Journal Title: Genes Dev. Volume: 29 Issue: 4 Pages: 409-425
  • DOI: 10.1101/gad.255331.114
  • Peer Reviewed / Open Access
• [Journal Article] Crucial role of the Rap G protein signal in Notch activation and leukemogenicity of T-cell acute lymphoblastic leukemia. (2015)
  • Author(s): Doi K, Imai T, Kressler C, Yagita H, Agata Y, Vooijs M, Hamazaki Y, Inoue J, Minato N.
  • Journal Title: Sci Rep. Volume: 5 Issue: 1 Pages: 7978-7985
  • DOI: 10.1038/srep07978
  • NAID: 120005555511
  • Peer Reviewed / Open Access
• [Presentation] E2A and CBP/p300 regulate chromosome dynamics of the TCRβ locus. (2017)
  • Author(s): Agata, Y, Wagatsuma K, Terada K, Tanaka H, Ikawa T, Masuda K, Kawamoto H, Kimura H
  • Organizer: 7th International Workshop of Kyoto T Cell Conference
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2017-03-15
  • Int'l Joint Research
• [Presentation] 転写因子E2AとCBP/p300が形成する核内構造体を足場としたTCRβ遺伝子再構成の制御機構. (2016)
  • Author(s): 寺田晃士、我妻慶祐、田中裕之、伊川友活、増田喬子、河本 宏、縣 保年
  • Organizer: 第26回 Kyoto T Cell Conference
  • Place of Presentation: 京都市
  • Year and Date: 2016-05-21
• [Presentation] E2A 転写因子 foci を足場とした T 細胞受容体遺伝子座の染色体ダイナミクス. (2016)
  • Author(s): 縣 保年、我妻慶祐、寺田晃士、安齋悠樹、田中裕之、伊川友活、増田喬子、河本 宏、木村 宏
  • Organizer: 第10回 日本エピジェネティクス研究会年会
  • Place of Presentation: 豊中市
  • Year and Date: 2016-05-20
• [Presentation] E2A転写因子ファクトリーを足場としたTCRβ遺伝子の染色体ダイナミクス (2015)
  • Author(s): 我妻慶祐、寺田晃士、安齋悠樹、田中裕之、伊川友活、増田喬子、河本 宏、湊 長博、縣 保年
  • Organizer: 第25回 Kyoto T Cell Conference
  • Place of Presentation: 京都市
  • Year and Date: 2015-05-15
• [Presentation] コヒーシン/CTCFとE2AによるT細胞初期分化の制御 (2014)
  • Author(s): 安齋悠樹、山下政克、伊川友活、増田喬子、河本 宏、湊 長博、縣 保年
  • Organizer: Kyoto T Cell Conference
  • Place of Presentation: 京都平安ホテル
  • Year and Date: 2014-05-16 – 2014-05-17
• [Remarks] 滋賀医科大学 生化学・分子生物学講座 分子生理化学部門 研究成果
  • URL: http://www.shiga-med.ac.jp/~hqbioch1/public_html/publish.html
• [Remarks] 滋賀医科大学 生化学・分子生物学講座 分子生理化学部門
  • URL: http://www.shiga-med.ac.jp/~hqbioch1/