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細胞の機能分化に関わる遺伝子制御ネッドワーク-遺伝子の階層的制御システム-

Research Project

Project/Area Number 05273102
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionKyoto University

Principal Investigator

岩渕 雅樹  京都大学, 大学院・理学研究科, 教授 (30000839)

Co-Investigator(Kenkyū-buntansha) 渡辺 武  九州大学, 生体防御医学研究所, 教授 (40028684)
堀越 正美  東京大学, 分子細胞生物学研究所, 助教授 (70242089)
鍋島 陽一  国立精神, 神経センター神経研, 部長 (60108024)
鈴木 義昭  岡崎国立共同研究機構, 基礎生物学研究所, 教授 (50132733)
垣塚 彰  京都大学, 大学院・医学研究科, 教授 (80204329)
安田 國雄  奈良先端科学技術大学院大学, バイオサイエンス科, 教授 (30025473)
原田 久志  東京大学, 医学部, 助手 (10222233)
佐竹 正延  東北大学, 加齢医学研, 教授 (50178688)
浜田 博司  東京都臨床研, 化学療法部, 部長 (00208589)
Project Period (FY) 1993 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥437,600,000 (Direct Cost: ¥437,600,000)
Fiscal Year 1996: ¥102,000,000 (Direct Cost: ¥102,000,000)
Fiscal Year 1995: ¥111,600,000 (Direct Cost: ¥111,600,000)
Fiscal Year 1994: ¥114,000,000 (Direct Cost: ¥114,000,000)
Fiscal Year 1993: ¥110,000,000 (Direct Cost: ¥110,000,000)
Keywords基本転写因子 / 特異的転写調節因子 / 転写因子復合体 / 転写因子ファミリー / 細胞機能制御 / 細胞増殖・分化 / 遺伝子欠損マウス / 転写因子ネットワーク / 機能ドメイン / 細胞機能 / 転写活性化機構 / 遺伝子特異的転写因子 / ノックアウト・マウス / 転写調節因子 / DNA非結合型因子 / 胚発生 / HBP-1a / IRF-1,-2 / 細胞分化
Research Abstract

平成8年度の研究成果を分担者ごとに以下に要約した。
(1)岩渕は、植物ヒストン遺伝子の転写因子のひとつHBP-1aサブファミリーである1a(17)のGCBモチーフと相互作用するタンパク質のcDNAをシロイヌナズナよりクローン化し、この因子の性質を調べた。その結果、このタンパク質がRNAヘリカーゼ活性を持つことを示した。
(2)垣塚は、ドミナント・ネガティブ作用を持つレチノイン酸受容体を軟骨細胞に発現させた形質転換マウスを用いて、レチノイン酸がホメオ遺伝子の発現制御を介して骨格形成に関わっていることを示した。
(3)佐竹は、転写因子PEBP2αBとPEBP2βの各遺伝子の欠損マウスを作出し、これを用いて解析した結果、両因子は生体内でヘテロダイマーとなって造血に等価な働きを持つことを示した。
(4)鈴木は、フィブロイン遺伝子エンハンサーIの転写因子SGF-2の精製に成功し、これが分子量1.1MDaの巨大複合体分子であることを明らかにした。
(5)鍋島は、マウス筋芽細胞において、MyoDの強制発現が筋管細胞へ分化しないreserve cellを筋管細胞へ変換させることを見い出した。
(6)浜田は、哺乳類の左右の位置情報に関与する遺伝子lefty-1とlefty-2をマウスより単離し、その転写調節領域を同定した。
(7)龍は、転写因子IRF-1を欠損したマウスは、タイプIヘルパーT細胞(TH1)の分化に異常を示し、またTH2の分化が抗進することを発見した。IRF-1の機能としては、IL-12のp40サブユニット転写制御や、IL-12への応答性などに作用していることを明らかにした。
(8)堀越は、TFIIDサブユニットとして、ヒストン相同性を持つタンパク因子の単離に成功し、ヒストンオクタマ-様構造モデルを提唱した。またTFIIDに相互作用するもので、クロマチン転写において働くコファクター因子を同定した。
(9)安田は、ニワトリのαA-クリスタリン遺伝子の転写因子であるL-mafの解析を、アフリカツメガエルやゼブラフィッシュについても解析した結果、mafが水晶体分化のマスター遺伝子になっていることを明らかにした。
(10)渡辺は、免疫細胞抗原受容体に会合する情報伝達分子HS1に結合する分子としてHAX-1を同定した。この因子の機能を調べた結果、この因子が細胞死抑制に働くことを明らかにした。

Report

(4 results)
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] Okanami,M.: "A bZIP-type protein interactng with the wheat transcription factor HBP-1a contains a novel transcription activation domain" Genes to Cells. 1. 87-99 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sakamoto,A.: "A zinc-finger-type transcription factor WZF-1 that binds to a novel cis-acting element of histone gene promoters supress its own promoter" Plant Cell Physiol.37. 557-562 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakayama,T.: "Dissection of the wheat transcription factor HBP-1a(17)revealed the modular structure of the activation domain" Mol.Gen.Genet.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Watanabe,G.: "Protein Kinase N(PKN)and PKN-related protein rhophilin as targets of the small GTPase Rho" Science. 271. 645-648 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Isizaki,T.: "The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase" EMBO Journal. 15. 1885-1893 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Early,E.: "Transgenic expression of PML-PARa impairs myelopoiesis" Proc.Natl.Acad.Sci.U.S.A.93. 7900-7904 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujioka,M.: "Runt domain partner proteins enhance DNA binding and transcriptional repression in cultured Drosophila cells" Genes to Cells. 1. 741-751 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Mach,V.: "The Drosophila Fork head factor directly controls larval salivary gland-specific expression of the glue protein gene Sgs3" Nucl.Acids.Res.24. 2387-2394 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nagata,T.: "Developmental expression of the Bombyx Antennapedia homologue and homeotic changes in the Nc mutant" Genes to Cells. 1. 555-568 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yoshida,S.: "Lysophosphatidic acid and bFGF control different modes in proliferating myoblasts" J.Cell Biol.132. 181-193 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sone,M.: "The Still life protein,homologous to GDP-GTP exchangers for rho-like GTPase,in synaptic terminals" Science. 275. 543-547 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Meno,C.: "Left-right asymmetric expression of the TGF β-family member lefty in mouse embryo" Nature. 381. 151-155 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Okazawa,H.: "Regulation of strial D1A dopamine receptor gene transcription by Bm-4" Proc.Natl.Acad.Sci.U.S.A.93. 11933-11938 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Choi,B.: "Isolation and characterization of a cDNA encoding a novel human transcription factor TFIID subunit containing similarities with histones H2B and H3" Gene. 169. 263-267 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nishikawa,J.: "Drosophila TAFII230 and the transciptional activator VP16 bind competitively to the TATA box-binding domain of TBP" Proc.Natl.Acad.Sci.U.S.A.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Duncan,M.K.: "Developmental regulation of the chicken bB1-crystallin promoter in transgenic mice" Mechnisms of Development. 57. 79-89 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Wang,J.: "Expression and function of Fas antigen on activated murine B cells" Eur.J.Immunol.26. 92-96 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Suzuki,Y: "HAX-1,a novel intracellular protein,localized on mitochondria,directly associates with HS1,a substrate of Src-family tyrosine kinases" J.Immunology. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Mikami,K.: "Developmental and tissue-specific regulation of the gene for the wheat basec/leucine zipper protein HBP-1a(17) in transgenic Arabidopsis plants." Mol.Gen.Genet.248. 573-582 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Satake,M.: "Expression of the runt domin-encoding PEBP2α genes in T cells during thymic development." Mol.Cell.Biol.15. 1662-1670 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mach,V.: "Silk gland factor-1 involved in the regulation of Bombyx sericin-1 gene contains fork head motif." J.Biol.Chem.270. 9340-9346 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hirata,J.: "Asymmetric segregation of the homeodomain protein Prospcro during Drosophila development." Nature. 377. 627-630 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yagami-Hiromasa,T.: "A metalloprotease-disintegrin participating in myoblast fusion." Nature. 377. 652-656 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakai,S.: "The POU-domain transcription factor Brn-2 is required for the determination of specific neuronal lineages in the hypothalamus of the mouse." Genes & Dev.(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Saijoh,Y.: "Identification of putative downstream genes of Oct-3,a pluripotent cell-specific transcription factor." Genes to Cells.(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tamura,T.: "An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes." Nature. 376. 596-599 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Vaughan,P.S.: "Activation of a cell-cycle regulated histone gene by the oncogenic transcription factor IRF-2." Nature. 377. 362-365 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ohkuma,T.: "Analysis of the role of TFIIE in basal transcription and TFIIH-mediated carboxyterminal domain phosphorylation through structure-function studies of TFIIE-α." Mol.Cell.Biol.15. 4856-4866 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ogawa,H.: "Localization,trafficking,and temperature-dependence of the Aquorea green fluorescent protein in cultured vertebrate cells." Proc.Natl.Acad.Sci.USA. 92. 11899-11903 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Taniuchi I.: "Antigen-receptor induced clonal expansion and deletion of lymphocytes are impaired in the mice lacking HS1 protein,a substrate of the antigen-receptor coupled tyrosine kinases." EMBO J.14(15). 3664-3678 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mikami,K.: "The HBP-1 family of wheat bZIP proteins interacts with overlapping cis-acting hexamer motifs of plant histone genes." J.Biol.Chem.269. 9974-9985 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Bae,S.C.: "PEBP2αB/mouse AML1 consists of multiple isoforms that posses differential transactivation potentials." Mol.Cell.Biol.14. 3242-3252 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Xu,P.-X.: "Promoter of the POU-M1/SGF-31 gene involved in the expression of Bombyx silk genes." J.Biol.Chem.269. 2733-2742 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Harada,H.: "Anti-oncogenic and oncogenic potentials of interferon regulatory factors-1 and -2." Science.259. 971-974 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kim.T.K.: "Effects of activation - defective TBP mutations on transcription initiation in yeast." Nature.369. 252-255 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kokubo,T.: "Molecular cloning of drosophila TFIID subunits." Nature.367. 484-487 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mikami,K.: "The HBP-1 family of wheat bZIP proteins interacts with overlapping cis-ctiting hexamer motifs of plant histone genes." J.Biol.Chem.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ogawa,E.: "PEBP2/PEA2 represents a family of transcription factor homologous to the products of the Drosophila runt gene and the human AML1 gene." Proc.Natl.Acad.Sci.USA.90. 6859-6863 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Fukuta,M.: "Molecular cloning of a POU domain-containing factor involved in the regulation of the Bombyx sericin-1 gene." J.Biol.Chem.268. 19471-19475 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nabeshima,Y.: "Myogenin gene disruption results in perinatal lethality because of severe muscle defect" Nature. 364. 532-535 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shimazaki,T.: "Hybrid cell extinction and re-expression of Oct-3 gene correlates with differentiation potential." EMBO J.12. 4489-4498 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Harada,H.: "Anti-oncogenic and oncogenic potentials of interferon regulatory factors-1 and-2." Science. 259. 971-974 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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