The mechanism for cell onocogenesis by chromosome-translocated chromatin remodeling factors

• Project/Area Number: 17013018
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: University of Tsukuba
• Principal Investigator: NAGATA Kyosuke University of Tsukuba, 大学院・人間総合科学研究科, 教授 (40180492)
• Co-Investigator(Kenkyū-buntansha): TAKEUCHI Kaoru 筑波大学, 大学院・人間総合科学研究科, 准教授 (00192162) ; OKUWAKI Mitsuru 筑波大学, 大学院・人間総合科学研究科, 准教授 (50322699)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥53,500,000 (Direct Cost: ¥53,500,000); Fiscal Year 2009: ¥10,700,000 (Direct Cost: ¥10,700,000); Fiscal Year 2008: ¥10,700,000 (Direct Cost: ¥10,700,000); Fiscal Year 2007: ¥10,700,000 (Direct Cost: ¥10,700,000); Fiscal Year 2006: ¥10,700,000 (Direct Cost: ¥10,700,000); Fiscal Year 2005: ¥10,700,000 (Direct Cost: ¥10,700,000)
• Keywords: 遺伝子 / 癌 / 分子生物学 / 染色体転座 / 転写 / クロマチン / 細胞死 / 細胞周期 / 白血病 / クロマチンリモデリング / ヒストンシペロン / 核膜孔 / トランスジェニックマウス / エピジェネティクス / ヒストンシャペロン / siRNA

Research Abstract

The aim of this study is to clarify the mechanism of oncogesis by TAF-I-CAN generated by chromosomal translocation and associated with undifferentiated acute myeloma. In TAF-I-CAN transgenic mice that we constructed, haemopoietic cell differentiation was blocked. When TAF-I-CAN in the cell that had been once transformed by TAF-I-CAN was eliminated, some oncogenic phenotypes were not cancelled, suggesting that an epigenetic change(s) is involved in cell transformation by TAF-I-CAN. TAF-I-CAN was found to inhibit NF-κB- and CBP-mediated transcription by their being mislocalized and squelched, respectively, by TAF-I-CAN. In addition, we found the possibility that RAG proteins and their cryptic signal sequences are involved in translocation for generation of TEL-AML1.

Research Products

• [Journal Article] Functional characterization of human Nucleosome Assembly Protein 1-like proteins as histone chaperones (2010)
  • Author(s): Okuwaki, M., et al
  • Journal Title: Genes to cells 15 Pages: 13-27
  • Peer Reviewed
• [Journal Article] Molecular cloning and characterization of porcine Mx2 gene (2009)
  • Author(s): Moroizumi, T., et al
  • Journal Title: Molecular Immunology 46 Pages: 858-865
  • Peer Reviewed
• [Journal Article] Epigenetic control of rDNA loci in response to intracellular energy status. (2008)
  • Author(s): Murayama A, Omori K, Fujimura A, Minami H, Yasuzawa-Tanaka K, Kuroda T, Oie S, Daitoku H, Okuwaki M, Nagata K, Fukamizu A, Kimura K, Shimizu T, Yanagisawa J.
  • Journal Title: Cell 133 Pages: 627-639
• [Journal Article] Spl-mediated transcription regulation of TAF1-alpha geneencoding a histone chaperone (2008)
  • Author(s): Asaka, et.al.
  • Journal Title: Biochem Biophys Res Commun 376 Pages: 665-670
  • Peer Reviewed
• [Journal Article] Epigenetic control of rDNA loci in response to intracellular energy status (2008)
  • Author(s): Murayama A, et.al.
  • Journal Title: Cell 133 Pages: 627-639
  • Peer Reviewed
• [Journal Article] Transcription regulation of rRNA gene by a multi-functional nucleolar protein, B23/nucleophosmin through its histone chaperonactivity (2008)
  • Author(s): Murano K, et.al.
  • Journal Title: Mol Cell Biol 28 Pages: 3114-3126
  • Peer Reviewed
• [Journal Article] The recurrent SET-NUP214 fusion as a new HOXA activationmechanism in pediatric T-cell acute lymphoblastic leukemia (2008)
  • Author(s): Vlierberghe V, et.al.
  • Journal Title: Blood 111 Pages: 4668-4680
  • Peer Reviewed
• [Journal Article] Impairment of erythroid and megakaryocytic differentiation by a Leukemia-associated and t(9 ; 9)-derived fusion gene product, SET/TAFIbetaCAN/Nun214 (2008)
  • Author(s): Saito S, et.al.
  • Journal Title: J Cell Physiol 214 Pages: 322-333
  • Peer Reviewed
• [Journal Article] Transcription regulatior of rRNA gene by a multi-functional nucleolar protein, B23/nucleophosmin through its histone chaperone activity (2008)
  • Author(s): K. Murano, et. al.
  • Journal Title: Mol. Cell. Biol. 35(印刷中)
  • Peer Reviewed
• [Journal Article] Impairment of erythroid and megakaryocytic differentiation by a leukemia-associated and t(9;9)-derived fusion gene product (2007)
  • Author(s): Saito S, Nouno K, Shimizu R, Yamamoto M, Nagata K.
  • Journal Title: SET/TAF-I β-CAN/Nup214. J. Cell. Physiol. 214 Pages: 322-333
• [Journal Article] Impairment of erythroid and megakaryocytic differentiation by a lcukemia-associated and t(9;9)-derived fusion gene product, SET/TAF-Iβ-CAN/Nup214 (2007)
  • Author(s): S. Saito, et. al.
  • Journal Title: J. Cell. Physiol. 214 Pages: 322-333
  • Peer Reviewed
• [Journal Article] Physical and functional interaction between a nucleolar protein nucleophosmin/B23 and adenovirus basic core proteins (2007)
  • Author(s): A. M. Samad, et. al.
  • Journal Title: FEBS Lett. 581 Pages: 3283-3288
  • Peer Reviewed
• [Journal Article] Histone acetylation-independenttranscription stimulation by a histone chaperone (2007)
  • Author(s): K. Kato, et. al.
  • Journal Title: Nucleic Acids Res. 35 Pages: 705-715
  • Peer Reviewed
• [Journal Article] Histone acetylationi-independent transcription stimulation by a histone chaperone. (2007)
  • Author(s): Kato, K., Miyaji-Yamaguchi, M., Okuwaki, M., Nagata, K.
  • Journal Title: Nucleic Acids Research 35 Pages: 705-715
• [Journal Article] Regulation of histone acetylation and nucleosome assembly by transcription factor JDP2 (2006)
  • Author(s): Jin C, Kato K, Chimura T, Yamasaki T, Nakade K, Murata T, Li H, Pan J, Zhao M, Sun K, Chiu R, Ito T, Nagata K, Horikoshi M, Yokoyama K.
  • Journal Title: Nature Structural & Molecular Biology 13 Pages: 331-338
• [Journal Article] Involvement of TAF-I/SET in transcription of adenovirus early genes as a positively acting factor. (2006)
  • Author(s): Haruki, H., Okuwaki, M., Miyagishi, M., Taira, K., Nagata, K.
  • Journal Title: Journal of Virology 80 Pages: 794-801
• [Journal Article] Binding modes of the precursor of adenovirus major core protein VII to DNA and Template Activating Factor-I : Implication for the mechanism of remodeling of the adenovirus chromatin. (2006)
  • Author(s): Gyurcsik, B., Haruki, H., Takahashi, T., Mihara, H., Nagata, K.
  • Journal Title: Biochemistry 45 Pages: 303-313
• [Journal Article] Regulation of histone acetylation and nucleosome assembly by transcription factor JDP2. (2006)
  • Author(s): Jin, C., Kato, K., Chimura, T., Yamasaki, T., Nakade, K., Murata, T., Li, H., Pan, J., Zhao, M., Sun, K., Chiu, R., Ito, T., Nagata, K, Horikoshi, M., Yokoyama, K.
  • Journal Title: Nature Strfuctural and Molecular Biology 13 Pages: 331-338
• [Journal Article] SET-mediated promoter hypoacetylation is a prerequisite for coactivation of the estrogen-responsive PS2 gene by PRMT1. (2006)
  • Author(s): Wagner, S., Weber, S., Kleinschmidt, M.A., Nagata, K., Bauer, U-T.
  • Journal Title: The Journal of Biological Chemistry 281 Pages: 27242-27250
• [Journal Article] Involvement of TAF-I/SET in transcription of adenovirus early genes as a positively acting factor. (2006)
  • Author(s): Haruki H, Okuwaki M, Miyagishi M, Taira K, Nagata K
  • Journal Title: Journal of Virology 80 Pages: 794-801
• [Journal Article] Binding modes of the precursor of adenovirus major core protein VII to DNA and Template Activating Factor-I : Implication for the mechanism of remodeling of the adenovirus chromatin. (2006)
  • Author(s): Gyuresik B, Haruki H, Takahashi T, Mihara H, Nagata K
  • Journal Title: Virology 45 Pages: 303-313
• [Journal Article] THAP7 associates with TAF-Iβ and inhibits histone acetylation to repress transcription. (2006)
  • Author(s): Macfarlan T, Parker J B, Nagata K, Chakravarti D
  • Journal Title: Molecular Endocrinology (In press)
• [Journal Article] Regulation of histone acetylation and nucleosome assembly by transcription factor JDP2. (2006)
  • Author(s): Jin C, Kato K, Chimura T, Yamasaki T, Nakade K, Murata T, Li H, Pan J, Zhao M, Sun K, Chiu R, Ito T, Nagata K, Horikoshi, Yokoyama K
  • Journal Title: Nature Structural & Molecular Biology (In press)
• [Journal Article] Synergistic action of MLL, a TRX protein with Template Activating Factor-I, a histone chaperone. (2005)
  • Author(s): Shimoyama T, Kato K, Miyaji-Yamaguchi M, Nagata K
  • Journal Title: FEBS Letters 579 Pages: 757-762
• [Journal Article] Assembly and disassembly of nucleosome core particles containing histone variants by human Nucleosome Assembly Protein-I. (2005)
  • Author(s): Okuwaki M, Kato K, Shimahara H, Tate S, Nagata K
  • Journal Title: Molecular and Cellular Biology 25 Pages: 10639-10651
• [Presentation] Molecular and Physiological Roles of Nuclear and Nucleolar Histone chaperones (2009)
  • Author(s): Nagata, K., et al
  • Organizer: Yokohama NMR 39^<th> Workshop
  • Place of Presentation: 横浜
  • Year and Date: 2009-11-12
• [Presentation] Molecular and pysiological roles of nucleolar histone chaperones. (2009)
  • Author(s): Nagata K, Kato K, Murano K.
  • Organizer: The 24th Naito Conference on Nuclear Dynamics and RNA.
  • Place of Presentation: Sapporo
• [Presentation] 細胞核内ループ構造によるTAF-Iαの転写制御機構 (2009)
  • Author(s): 浅賀正充, 他
  • Organizer: 第8回核ダイナミクス研究会
  • Place of Presentation: 修善寺
• [Presentation] 分裂期リン酸化による核小体タンパク質 Nucleophosmin/B23のクロマチン制御機能の調節 (2009)
  • Author(s): 久岡美晴, 他
  • Organizer: 第8回核ダイナミクス研究会
  • Place of Presentation: 修善寺
• [Presentation] Molecular and Pysiological Roles of Nucleolar Histone Chaperones (2009)
  • Author(s): Nagata, K., et al
  • Organizer: The 24^<th> Naito Conference on Nuclear Dynamics and RNA
  • Place of Presentation: 札幌
• [Presentation] Transcription regulation of TAF-1α promoter through DNA loop structure (2009)
  • Author(s): 浅賀正充 , et al
  • Organizer: EMBO Conference Series Nuclear Structure and Dynamics
  • Place of Presentation: France Domaine de Mousquety
• [Presentation] HMGBタンパク質による異常なRAG依存的DNA切断活性促進 (2009)
  • Author(s): 沼田和志, 他
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] Functions of a linker histone chaperone in regulation of chromatin dynamics (2009)
  • Author(s): 加藤広介, 他
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Knock out of TAF-1, a histone chaperone, causes developmental defects and embryonic lethality (2009)
  • Author(s): 村野健作, 他
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] HMGB1-dependent stimulation of RAG-mediated cleavage at cryptic RSS associated with chromosomal translocation (2009)
  • Author(s): 沼田和志, 他
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] アデノウイルスクロマチンの構造変換による転写制御機構の解析 (2008)
  • Author(s): 小松哲郎、他
  • Organizer: 第5回ウイルス学キャンプ
  • Place of Presentation: 湯河原
• [Presentation] The mechanism of transcription and chromatin structure regulation by histone chaperone TAF-I (2008)
  • Author(s): Kato K, et.al.
  • Organizer: The 21^<ST> NAITO CONFERENCE on Nuclear Dynamics and RNA [I]
  • Place of Presentation: 山梨
• [Presentation] ヒストンシャペロンと核膜孔構成因子の融合タンパク質SET/TAF-1-Nup2141CANによるCBPの活性制御機構 (2008)
  • Author(s): 斎藤祥子、他
  • Organizer: 第67回日本癌学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] 染色体転座形成におけるRAGのHGMタンパク質依存的なDNA切断制御機構 (2008)
  • Author(s): 沼田和志、他
  • Organizer: 第31回日本分子生物学会学術集会
  • Place of Presentation: 神戸
• [Presentation] 感染細胞内におけるアデノ・ウイルスクロマチンの構造変換による転写制御 (2008)
  • Author(s): 小松哲郎、他
  • Organizer: 第31回日本分子生物学会学術集会
  • Place of Presentation: 神戸
• [Presentation] 転写因子PU.1と核膜孔タンパク質CANの相互作用 (2008)
  • Author(s): 加藤寛之、他
  • Organizer: 第31回日本分子生物学会学術集会
  • Place of Presentation: 神戸
• [Presentation] RAGによるTEL-AML1染色体転座の酵素機構 (2007)
  • Author(s): 沼田和志・ほか
  • Organizer: 第30回日本分子生物学会年会及び第80回日本生物化学大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] Increase of hematopoietic progenitors but impairment of erythroid and megakaryocytic differentiation in transgenic mice expressing SET-CAN (2007)
  • Author(s): S., Saito, et. al.
  • Organizer: Gordon Research Conference-STEM CELLS&CANCER-
  • Place of Presentation: Bigsky(USA)
  • Year and Date: 2007-09-12
• [Presentation] Regulation of histone acetylation and nucleosome assembly by transcription factor JDP2 (2006)
  • Author(s): Jin C, Kato K, Chimura T, Yamasaki T, Nakade K, Murata T, Li H, Pan J, Zhao M, Sun K, Chiu R, Ito T, Nagata K, Horikoshi M, Yokoyama K.
  • Organizer: Nature Structural & Molecular Biology
• [Book] 目的別で選べるタンパク質発現プロトコール (2010)
  • Author(s): 永田恭介
  • Total Pages: 267
  • Publisher: 羊土社
• [Book] 分子細胞生物学辞典(第2版) (2008)
  • Author(s): 永田恭介
  • Total Pages: 1184
  • Publisher: 東京化学同人
• [Book] ヒトの生物学(翻訳) (2007)
  • Author(s): 永田恭介
  • Total Pages: 543
  • Publisher: 丸善株式会社
• [Book] Nuclear Dynamics-Molecular Biology and Visualozation of the Nucleus-. (2006)
  • Author(s): Nagata K, Takeyasu K.
  • Total Pages: 279
  • Publisher: Springer
• [Book] Nuclear Dynamics -Molecular Biology and Visualozation of the Nucleus- (2006)
  • Author(s): Nagata, K., Takeyasu, K.
  • Total Pages: 279
  • Publisher: Springer
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/basicmed/infectionbiology/virology/Site_2/Welcome.html
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/basic-med/infectionbiology/virology/Site_2/Welcome.html
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  • URL: http://www.md.tsukuba-ac.jp/basic-med/infectionbiology/virology/Site_2/Welcome.html
• [Patent(Industrial Property Rights)] 酵母細胞を用いたインフルエンザウイルスゲノムの複製・転写系 (2007)
  • Inventor(s): 永田, 恭介・内藤, 忠相
  • Industrial Property Rights Holder: 国立大学法人筑波大学
  • Filing Date: 2007-05-15
  • Overseas
• [Patent(Industrial Property Rights)] 酵母を用いたインフルエンザウイルスゲノムの複製・転写系 (2005)
  • Inventor(s): 永田 恭介, 内藤 忠相
  • Industrial Property Rights Holder: 筑波大学
  • Industrial Property Number: 2005-334549
  • Filing Date: 2005-11-18