Elucidation of transcriptional regulation by histone modification pattern

• Project/Area Number: 26293059
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: NAKAYAMA Keiko 東北大学, 医学(系)研究科(研究院), 教授 (60294972)
• Co-Investigator(Kenkyū-buntansha): 舟山 亮 東北大学, 医学(系)研究科(研究院), 助教 (20452295) ; 細金 正樹 東北大学, 医学(系)研究科(研究院), 助手 (30734347)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2014: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: ヒストン修飾 / Ｂリンパ球 / ChIPシークエンス / 乳癌細胞株 / リンパ球 / Bリンパ球 / インスリン分泌細胞

Outline of Final Research Achievements

TGF-β treatment to breast cancer cell lines induces epithelial-mesenchymal transition. We confirmed suppression of EZH2 expression by shRNA decreased modification levels of Histone H3K27me3. With this method, we analyzed the effect of suppression of H3K27me3 modification on transcript. Contrary to expectations, suppression of H3K27me3 did not cause a major effect.
Next to breast cancer cell lines, we analyzed EZH2 deficient B lymphocytes. As we expected, modification of H3K27me3 in these downregulated and we obtained list of transcriptional activated genes. We also analyzed the modification level of H3K4me1 as a marker of enhancer activity. We identified the region where H3K4me1 increased after EZH2 deletion. However, we could not recognize which genes were regulated by corresponding enhancers.

Research Products

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• [Journal Article] The aryl hydrocarbon receptor AhR links atopic dermatitis and air pollution via induction of the neurotrophic factor artemin. (2017)
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• [Journal Article] Dramatic response after functional hemispherectomy in a patient with epileptic encephalopathy carrying a de novo COL4A1 mutation. (2017)
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• [Journal Article] Ubiquitylation of Ku80 by RNF126 Promotes Completion of Nonhomologous End Joining-Mediated DNA Repair. (2017)
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• [Journal Article] Wnt-beta-catenin signaling regulates ABCC3 (MRP3) transporter expression in colorectal cancer. (2016)
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• [Journal Article] Lack of genetic variation prevents adaptation at the geographic range margin in a damselfly. (2016)
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• [Journal Article] The Tohoku Medical Megabank Project: Design and Mission (2016)
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  • Journal Title: Journal of Epidemiology Volume: 26 Issue: 9 Pages: 493-511
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  • NAID: 130005409018
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• [Journal Article] Lack of Transcription Triggers H3K27me3 Accumulation in the Gene Body. (2016)
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  • Journal Title: Cell Rep. Volume: 16 Pages: 696-706
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• [Journal Article] The double knockout of Bach1 and Bach2 in mice reveals shared compensatory mechanisms in regulating alveolar macrophage function and lung surfactant homeostasis. (2016)
  • Author(s): Ebina-Shibuya, R., Watanabe-Matsui, M., Matsumoto, M., Itoh-Nakadai, A., Funayama, R., Nakayama, K., Muto, A., Igarashi, K.
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• [Journal Article] Genomewide approaches for BACH1 target genes in mouse embryonic fibroblasts showed BACH1-Pparg pathway in adipogenesis. (2016)
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• [Journal Article] Protein monoubiquitylation: targets and diverse functions (2015)
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• [Journal Article] Role of the Atg9a gene in intrauterine growth and survival of fetal mice. (2015)
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• [Journal Article] The artificial loss of Runx1 reduces the expression of quiescence-associated transcription factors in CD4(+) T lymphocytes. (2015)
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  • Journal Title: Mol Immunol Volume: 68 Pages: 223-233
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• [Journal Article] Rho-kinase inhibition during early cardiac development causes arrhythmogenic right ventricular cardiomyopathy in mice. (2015)
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• [Journal Article] S6 Kinase- and beta-TrCP2-Dependent Degradation of p19Arf Is Required for Cell Proliferation (2015)
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• [Journal Article] CRL4 E3 Ligase Promotes Monoubiquitylation and Chromatin Binding of TET Dioxygenases (2015)
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  • Journal Title: Mol Cell Volume: 57 Pages: 247-260
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• [Journal Article] Identification of acquired mutations by whole-genome sequencing in GATA-2 deficiency evolving into myelodysplasia and acute leukemia. (2014)
  • Author(s): Fujiwara, T., Fukuhara, N., Funayama, R., Nariai, N., Kamata, M., Nagashima, T., Kojima, K., Onishi, Y., Sasahara, Y., Ishizawa, K., Nagasaki, M., Nakayama, K. & Harigae, H
  • Journal Title: Annals of Hematology Volume: 93 Pages: 1515-1522
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• [Journal Article] HCV infection enhances Th17 commitment, which could affect the pathogenesis of autoimmune diseases (2014)
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  • Journal Title: PLoS One. Volume: 9(6)
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• [Journal Article] GNE myopathy associated with congenital thrombocytopenia: a report of two siblings. (2014)
  • Author(s): Izumi R, Niihori T, Suzuki N, Sasahara Y, Nishiyama A, Nishiyama S, Endo K, Kato M, Warita H, Konno H, Tateyama M, Nagashima T, Funayama R, Nakayama K, Kure S, Matsubara Y, Aoki Y, Aoki M.
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• [Presentation] Molecular analysis of Amyotrophic Lateral Sclerosis associated Cyclin F mutants. (2016)
  • Author(s): Yujiao Yu, Akane Morohoshi, Tadashi Nakagawa, Keiko Nakayama.
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-12-01
• [Presentation] ユビキチン化によるFACT複合体の機能制御 (2016)
  • Author(s): 諸星茜、中川直、中山啓子
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-12-01
• [Presentation] H3K27ヒストン修飾によるエンハンサー制御のゲノムワイド解析 (2016)
  • Author(s): 細金正樹、中山啓子
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-12-01
• [Presentation] 大腸がんにおけるタンパク質シトルリン化酵素PADI2の役割 (2016)
  • Author(s): 舟山亮、谷口肇、水間正道、藤島史喜、小林実、大沼忍、海野倫明、中山啓子
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-12-01
• [Presentation] Reactivation of cell proliferation by continuous TGF-β treatment. (2016)
  • Author(s): Tadashi Nakagawa, Masaki Hosogane, Ryo Funayama, Keiko Nakayama.
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-11-30
• [Presentation] 大腸癌で発現が抑制されるPeptidylarginine deiminase2の機能解析 (2016)
  • Author(s): 谷口肇、舟山亮、小林実、高館達之、阿部友哉、水間正道、藤島史喜、大沼忍、内藤剛、海野倫明、中山啓子
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2016-10-06
• [Presentation] がん原遺伝子RASによる遺伝子サイレンシングの分子機構の解析 (2015)
  • Author(s): 舟山亮、細金正樹、長嶋剛史、中山啓子
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] TGF-β刺激によるTFIID構成因子TAF7の分解とその役割の解明 (2015)
  • Author(s): 中川直、細金正樹、舟山亮、中山啓子
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] セルトリ細胞特異的β-TrCPノックアウトマウスの解析 (2015)
  • Author(s): 諸星茜、中川直、中野星児、中山啓子.
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] マウスES細胞におけるgemininの細胞周期と分化に対する制御. (2014)
  • Author(s): 福本恵美子, Kundu, Lena Rani, 佐藤聡一郎, 細金正樹 & 中山啓子
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-27
• [Presentation] H3K27me3修飾パターン形成過程の時系列解析 (2014)
  • Author(s): 細金正樹, 舟山亮, 城田松之 & 中山啓子
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-27
• [Presentation] 精子形成におけるE3ユビキチンリガーゼβ-TrCPの新規基質の同定と解析 (2014)
  • Author(s): 久志瞭, 中川直, 中野星児, 遠藤尚博 & 中山啓子
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-25
• [Presentation] TFIID complex changes accompany epithelial-mesenchymal transition (EMT). (2014)
  • Author(s): Nakagawa, Tadashi & Nakayama, Keiko
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-25
• [Presentation] がん遺伝子による転写変化とエピゲノム変化 (2014)
  • Author(s): 中山啓子
  • Organizer: 第23回長崎障害者支援再生医療研究会
  • Place of Presentation: 長崎大学医学部良順会館（長崎県長崎市）
  • Year and Date: 2014-11-04
  • Invited
• [Remarks] 東北大学がん医学コアセンター細胞増殖制御分野
  • URL: http://www.devgen.med.tohoku.ac.jp/
• [Remarks] がん医学コアセンター 細胞増殖制御分野
  • URL: http://www.devgen.med.tohoku.ac.jp/index.html