Acetylation network via TIP60 complex focusing on damaged chromatin dynamics

• Project/Area Number: 26281020
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Kyoto University
• Principal Investigator: Ikura Tsuyoshi 京都大学, 放射線生物研究センター, 准教授 (70335686)
• Co-Investigator(Renkei-kenkyūsha): MATSUDA Tomonari 京都大学, 工学研究科附属 流域圏総合環境質研究センター, 准教授 (50273488) ; TASHIRO Satoshi 広島大学, 原爆放射線医科学研究所, 教授 (20243610)
• Research Collaborator: IKURA Masae
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
• Keywords: アセチル化 / ヒストンH2AX / TIP60 / リン酸化 / DNA損傷応答 / TIP60ヒストンアセチル化酵素複合体 / H2AX

Outline of Final Research Achievements

We investigated how damaged chromatin dynamics via histone H2AX acetylation by TIP60 histone acetyltransferase complex affects the activation of DNA damage signaling via H2AX-phosphorylation. We found that both acetylation and phosphorylation of H2AX after induction of DNA damage are not required for the initial recruitment of NBS1 to DNA damage sites but for the maintenance of NBS1 at DNA damage sites in different ways. Our findings demonstrate that the phosphorylation of H2AX function as an anchor to maintain NBS1 at DNA damage sites whereas, the acetylation of H2AX by TIP60 complex has an important role to prevent the spreading of NBS1 signaling to undamaged regions.

Research Products

• [Journal Article] Xeroderma pigmentosum group C protein interacts with histones: regulation by acetylated states of histone H3. (2017)
  • Author(s): Kakumu E
  • Journal Title: Genes Cells. Volume: 3 Issue: 3 Pages: 310-327
  • DOI: 10.1111/gtc.12479
  • Peer Reviewed / Open Access
• [Journal Article] Histone H4 lysine 20 acetylation is associated with gene repression in human cells. (2016)
  • Author(s): Kaimori, J. Y., Maehara, K., Hayashi-Takanaka, Y., Harada, A., Fukuda, M., Yamamoto, S., Ichimaru, N., Umehara, T., Yokoyama, S., Matsuda, R., Ikura, T., Nagao, K., Obuse, C., Nozaki, N., Takahara, S., Takao, T., Ohkawa, Y., Kimura, H., and Isaka, Y.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 24318-24318
  • DOI: 10.1038/srep24318
  • NAID: 120005770760
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Histone H2A T120 Phosphorylation Promotes Oncogenic Transformation via Upregulation of Cyclin D1. (2016)
  • Author(s): Aihara H
  • Journal Title: Mol. Cell. Volume: 64 Issue: 1 Pages: 176-188
  • DOI: 10.1016/j.molcel.2016.09.012
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Coordinated regulation of TIP60 and PARP-1 in damaged chromatin dynamics. (2016)
  • Author(s): Ikura M
  • Journal Title: Mol. Cell. Biol. Volume: Epub ahead of print Issue: 10 Pages: 1595-1607
  • DOI: 10.1128/mcb.01085-15
  • Peer Reviewed / Open Access
• [Journal Article] Disruption of DNA Damage-Response by Propyl Gallate and 9-Aminoacridine (2016)
  • Author(s): Matsuda S
  • Journal Title: Toxicol. Sci. Volume: 150 Issue: 2 Pages: 1-12
  • DOI: 10.1093/toxsci/kfw039
  • Peer Reviewed
• [Journal Article] SMARCAD1 is an ATP-dependent stimulator of nucleosomal H2A acetylation via CBP, resulting in transcriptional regulation. (2016)
  • Author(s): Doiguchi M
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 20179-20179
  • DOI: 10.1038/srep20179
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Epigenetic Regulation of the Blimp-1 Gene (Prdm1) in B Cells Involves Bach2 and Histone Deacetylase 3* (2016)
  • Author(s): Tanaka H
  • Journal Title: JBC Volume: 291 Issue: 12 Pages: 6316-6330
  • DOI: 10.1074/jbc.m116.713842
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Acetylation of Histone H2AX at Lys 5 by the TIP60 Histone Acetyltransferase Complex Is Essential for the Dynamic Binding of NBS1 to Damaged Chromatin. (2015)
  • Author(s): Ikura M
  • Journal Title: Mol. cell. Biol. Volume: 35 Issue: 24 Pages: 4147-4157
  • DOI: 10.1128/mcb.00757-15
  • Peer Reviewed
• [Journal Article] Nuclear pyruvate kinase M2 complex serves as a transcriptional coactivator of arylhydrocarbon receptor. (2015)
  • Author(s): Shun Matsuda, Jun Adachi, Masaru Ihara, Nobuhiro Tanuma, Hiroshi Shima, Akira Kakizuka, Masae Ikura, Tsuyoshi Ikura, Tomonari Matsuda
  • Journal Title: Nucleic Acids Res Volume: 44(2) Issue: 2 Pages: 636-647
  • DOI: 10.1093/nar/gkv967
  • NAID: 120005818255
  • Peer Reviewed / Open Access
• [Journal Article] Structural basis of a nucleosome containing histone H2A.B/H2A.Bbd that transiently associates with reorganized chromatin (2015)
  • Author(s): Arimura Y
  • Journal Title: Sci. Rep. Volume: 5 Issue: 1 Pages: 09628-09628
  • DOI: 10.1038/srep09628
  • Peer Reviewed / Open Access
• [Journal Article] hCAS/CSE1L regulates RAD51 distribution and focus formation for homologous recombinational repair (2015)
  • Author(s): 1.Okimoto S, Sun J, Fukuto A, Horikoshi Y, Matsuda S, Matsuda T, Ikura M, Ikura T, Machida S, Kurumizaka H, Miyamoto Y, Oka M, Yoneda Y, Kiuchi Y, Tashiro S.
  • Journal Title: Genes Cells. Volume: 20 Issue: 9 Pages: 681-94
  • DOI: 10.1111/gtc.12262
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Absolute quantification of acetylation and phosphorylation of the histone variant H2AX upon ionizing radiation reveals distinct cellular responses in two cancer cell lines (2015)
  • Author(s): Matsuda S
  • Journal Title: Radiat. Environ. Biophys. Volume: 54 Issue: 4 Pages: 403-411
  • DOI: 10.1007/s00411-015-0608-3
  • Peer Reviewed
• [Journal Article] SUMOylation of xeroderma pigmentosum group C protein regulates DNA damage recognition during nucleotide excision repair (2015)
  • Author(s): Akita M
  • Journal Title: Sci. Rep. Volume: 5 Issue: 1 Pages: 10984-10984
  • DOI: 10.1038/srep10984
  • Peer Reviewed / Open Access
• [Journal Article] Absolute quantification of γH2AX using liquid chromatography-triple quadrupole tandem mass spectrometry (2015)
  • Author(s): Matsuda, S., Ikura, T., Matsuda, T.
  • Journal Title: Analytical and Bioanalytical Chemistry Volume: in press Issue: 18 Pages: 5521-5527
  • DOI: 10.1007/s00216-015-8725-z
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Regulation of homologous recombinational repair by lamin B1 in radiation-induced DNA damage. (2015)
  • Author(s): Liu NA
  • Journal Title: FASEB J. Volume: 14 Pages: 265546-265546
  • Peer Reviewed
• [Journal Article] Reorganization of Damaged Chromatin by the Exchange of Histone Variant H2A.Z-2. (2014)
  • Author(s): Nishibuchi I
  • Journal Title: Int J Radiat Oncol Biol Phys. Volume: 89 Issue: 4 Pages: 736-744
  • DOI: 10.1016/j.ijrobp.2014.03.031
  • Peer Reviewed / Open Access
• [Journal Article] Nap1 stimulates homologous recombination by RAD51 and RAD54 in higher-ordered chromatin containing histone H1. (2014)
  • Author(s): Machida, S., Takaku, M., Ikura, M., Sun, J., Suzuki, H., Kobayashi, W., Kinomura, A., Osakabe, A., Tachiwana, H., Horikoshi, Y., Fukuto, A., Matsuda, R., Ura, K., Tashiro, S., Ikura, T., and Kurumizaka, H.
  • Journal Title: Scientific Rep. Volume: 4 Issue: 1 Pages: 4863-4863
  • DOI: 10.1038/srep04863
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] FANCD2 Binds CtIP and Regulates DNA-End Resection during DNA Interstrand Crosslink Repair. (2014)
  • Author(s): Unno J
  • Journal Title: Cell Rep. Volume: 7 Issue: 4 Pages: 1039-1047
  • DOI: 10.1016/j.celrep.2014.04.005
  • Peer Reviewed / Open Access
• [Presentation] タンパク質複合体解析の現状と今後への挑戦 (2016)
  • Author(s): 井倉 毅
  • Organizer: 岡崎フラグメント50周年シンポジウム
  • Place of Presentation: 名古屋市
  • Year and Date: 2016-12-21
  • Invited
• [Presentation] ゲノムストレス応答の多様性を数理的アプローチで理解する (2016)
  • Author(s): 井倉 毅
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-11-30
• [Presentation] リンカーヒストンH1を含むクロマチンでの相同組換え反応 (2016)
  • Author(s): 町田晋一
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-11-30
• [Presentation] RAD51による相同組換え修復の制御機構 (2016)
  • Author(s): 堀越保則
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-11-30
• [Presentation] DNAチェックポイント因子Rad9の機能制御を担うCdk-Plk1依存的機構の意義 (2016)
  • Author(s): 郡司 未佳
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-11-30
• [Presentation] がん細胞で高頻度におこるヒストンH2B点変異体はヌクレオソーム構造および細胞増殖に影響を与える (2016)
  • Author(s): 野田真美子
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-11-30
• [Presentation] Molecular mechanism of etoposide induced 11q23 chromosome translocations. (2016)
  • Author(s): 孫 継英
  • Organizer: 日本放射線影響学会 第59回大会
  • Place of Presentation: 広島市
  • Year and Date: 2016-10-26
• [Presentation] がん研究入門コース1「がん研究におけるクロマチン生物学」 (2016)
  • Author(s): 井倉 毅
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-10-06
  • Invited
• [Presentation] DNA損傷応答におけるヒストンH2AX複合体モジュールのダイナミクス (2016)
  • Author(s): 井倉 毅
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台市
  • Year and Date: 2016-09-25
• [Presentation] Molecular mechanism of etoposide induced 11q23 chromosome translocations. (2016)
  • Author(s): Jiying Sun
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台市
  • Year and Date: 2016-09-25
• [Presentation] クロマチンの動的変化に着目したゲノム損傷応答の多様性の理解 (2016)
  • Author(s): 井倉 毅
  • Organizer: 日本環境変異原学会・変異機構研究会・第29回 夏の学校
  • Place of Presentation: 京都府京北町
  • Year and Date: 2016-09-10
  • Invited
• [Presentation] クロマチン制御から見たDNA 損傷応答研究の現状と今後の展望 (2016)
  • Author(s): 井倉 毅
  • Organizer: 東北大学加齢医学研究所セミナー
  • Place of Presentation: 仙台市
  • Year and Date: 2016-01-15
  • Invited
• [Presentation] DNA損傷応答における動的クロマチン平衡とその意義 (2015)
  • Author(s): 井倉 毅
  • Organizer: 第38回日本分子生物学会年会第88回日本生化学会合同大会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-12-01
• [Presentation] ヒストン化学修飾から見たDNA修復研究の展望 (2015)
  • Author(s): 井倉 毅
  • Organizer: 第38回日本分子生物学会年会第88回日本生化学会合同大会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] DNAチェックポイント因子Rad9の分解を促進するCdk-Plk1依存的機構 (2015)
  • Author(s): 郡司未佳
  • Organizer: 第38回日本分子生物学会年会第88回日本生化学会合同大会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-12-01
• [Presentation] ピルビン酸キナーゼとピルビン酸デヒドロゲナーゼ複合体によるアセチルCoAの治産池消モデル (2015)
  • Author(s): 松田俊
  • Organizer: 第38回日本分子生物学会年会第88回日本生化学学会合同大会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-12-01
• [Presentation] Involvement of a chromatin remodeling factor in chromosomal translocations (2015)
  • Author(s): 孫継英
  • Organizer: 第38回日本分子生物学会年会第88回日本生化学会合同大会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-12-01
• [Presentation] アセチル化を介した損傷クロマチンダイナミクス (2015)
  • Author(s): 井倉 毅
  • Organizer: 横浜市立大学生命医科学研究科セミナー
  • Place of Presentation: 横浜市
  • Year and Date: 2015-11-17
  • Invited
• [Presentation] Molecular mechanism of etoposide induced 11q23 chromosome translocation. (2015)
  • Author(s): Jiying Sun
  • Organizer: 第74回日本癌学会学術総会,
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-10-08
• [Presentation] The Role of Histone H2AX Dynamics in DNA Damage Responsehe Role of Histone H2AX Dynamics in DNA Damage Response (2015)
  • Author(s): Tsuyoshi Ikura
  • Organizer: 第15回国際放射線研究会議（ICRR2015）
  • Place of Presentation: 京都市
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] Acetylation-dependent positive feedback loop regulation in dynamic chromatin equilibrium (2015)
  • Author(s): Tsuyoshi Ikura
  • Organizer: Institute for Protein Research (IPR) Seminar
  • Place of Presentation: 吹田市
  • Year and Date: 2015-05-18
  • Invited
• [Presentation] Chromatin dynamics in DNA damage response (2015)
  • Author(s): Tsuyoshi Ikura
  • Organizer: First DSV/CEA-RBC joint workshop
  • Place of Presentation: France
  • Year and Date: 2015-04-08
  • Int'l Joint Research / Invited
• [Presentation] Histone H2AX dynamics coordinates DNA repair with chromatin reorganization (2015)
  • Author(s): Masae Ikura
  • Organizer: The 5th International Symposium of RIRBM, Hiroshima University
  • Place of Presentation: 広島市
  • Year and Date: 2015-03-02 – 2015-03-03
• [Presentation] The coupling of epigenetic regulation with metabolism in cancer (2015)
  • Author(s): Tsuyoshi Ikura
  • Organizer: The 30th RBC-NIRS International Symposium "Frontier Radiation Biology, Now and In the future."
  • Place of Presentation: 京都市
  • Year and Date: 2015-02-20 – 2015-02-21
  • Invited
• [Presentation] The role of the pyruvate kinase M2 (PKM2) in the Arylhydrocarbon Receptor-mediated Transcription (2015)
  • Author(s): Tsuyoshi Ikura
  • Organizer: 5th meeting of the Asian Forum for chromatin and chromosome Biology
  • Place of Presentation: Bungalow, India.
  • Year and Date: 2015-01-13 – 2015-01-19
  • Invited
• [Presentation] The role of histone H2AX dynamics in DNA damage response (2014)
  • Author(s): Tsuyoshi Ikura
  • Organizer: The 4D Nucleome 2014
  • Place of Presentation: 広島市
  • Year and Date: 2014-12-17 – 2014-12-20
• [Presentation] Nap1 is required for the homologous recombination reaction in higher-order chromatin containing histone H1 (2014)
  • Author(s): Shinichi Machida
  • Organizer: The 4D Nucleome 2014
  • Place of Presentation: 広島市
  • Year and Date: 2014-12-17 – 2014-12-20
• [Presentation] Nap1は高次クロマチンでの相同組換えを促進する (2014)
  • Author(s): 町田晋一
  • Organizer: 第32回 染色体ワークショップ
  • Place of Presentation: 広島市
  • Year and Date: 2014-12-15 – 2014-12-17
• [Presentation] 翻訳後修飾を介した色素性乾皮症遺伝子産物の機能制御 (2014)
  • Author(s): 秋田 真季
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] ＤＮＡ複製チェックポイント蛋白質Rad9は、PLK1依存的に分解をうける (2014)
  • Author(s): 郡司 未佳
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 生細胞イメージングを用いたDNA損傷修復過程におけるヒストン修飾動態とクロマチン凝集の解析 (2014)
  • Author(s): 大倉 健太
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] DNA損傷応答におけるヒストンアセチル化を介したクロマチン動的制御とその意義 (2014)
  • Author(s): 井倉 毅
  • Organizer: 平成26年度遺伝研研究会「クロマチンにおけるゲノムDNAの機能発現メカニズム」
  • Place of Presentation: 静岡県三島市
  • Year and Date: 2014-10-30 – 2014-10-31
  • Invited
• [Presentation] Activation of the SUMO modification system is required for the accumulation of RAD51 at sites containing DNA damage (2014)
  • Author(s): Tsuyoshi Ikura
  • Organizer: 第５回日米修復会議
  • Place of Presentation: 徳島県鳴門市
  • Year and Date: 2014-10-28 – 2014-10-29
• [Presentation] DNA損傷応答におけるヒストンH2AX化学修飾の時空間的制御 (2014)
  • Author(s): 井倉 毅
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都市
  • Year and Date: 2014-10-15 – 2014-10-16
  • Invited
• [Presentation] DNA損傷応答におけるポジティブフィードバック制御を介した高次クロマチン構造の役割 (2014)
  • Author(s): 井倉 毅
  • Organizer: 神戸大学セミナー
  • Place of Presentation: 神戸市
  • Year and Date: 2014-06-04
  • Invited
• [Presentation] Chromatin dynamics in DNA damage response (2014)
  • Author(s): Masae Ikura
  • Organizer: IIAS Research Conference 2014 Chromatin decoding
  • Place of Presentation: 京都市
  • Year and Date: 2014-05-12 – 2014-05-14
• [Presentation] DNA損傷初期応答におけるヒストンシグナルネットワークの解明 (2014)
  • Author(s): 井倉 毅
  • Organizer: 新学術領域 ゲノム普遍的制御 第5回領域班会議
  • Place of Presentation: 徳島県鳴門市
  • Year and Date: 2014-05-07 – 2014-05-09