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細胞の機能分化に関わる遺伝子制御ネットワーク-転写因子間相互作用-

Research Project

Project/Area Number 05273101
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionTohoku University (1994-1996)
Tokyo Institute of Technology (1993)

Principal Investigator

藤井 義明 (1994-1996)  東北大学, 大学院・理学研究科, 教授 (00098146)

半田 宏 (1993)  東京工業大学, 生命理工学部, 教授 (80107432)

Co-Investigator(Kenkyū-buntansha) 山本 雅之  筑波大学, 基礎医学系, 教授 (50166823)
半田 宏  東京工業大学, 生命理工学部, 教授 (80107432)
長田 重一  大阪大学, 医学部, 教授 (70114428)
石井 俊輔  理科学研究所, 分子遺伝, 主任研究員 (00124785)
審良 静男  兵庫医科大学, 教授 (50192919)
田村 隆明  千葉大学, 理学部, 教授 (30112692)
村松 正実  埼玉医科大学, 教授 (10035454)
藤沢 順一  東京大学, 医科学研究所, 助手 (40181341)
藤井 義明  東北大学, 理学部, 教授 (00098146)
Project Period (FY) 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥316,000,000 (Direct Cost: ¥316,000,000)
Fiscal Year 1996: ¥76,000,000 (Direct Cost: ¥76,000,000)
Fiscal Year 1995: ¥79,000,000 (Direct Cost: ¥79,000,000)
Fiscal Year 1994: ¥80,000,000 (Direct Cost: ¥80,000,000)
Fiscal Year 1993: ¥81,000,000 (Direct Cost: ¥81,000,000)
Keywords遺伝子破壊マウス / コアクチベータ- / STAT / 転写伸長 / Myb / GATA-1 / Ahリセプター / ダイオキシン / 遺伝子欠損マウス / 種特異的転写 / リン酸化 / ホモダイマー / ヘテロダイマー / 相互作用 / マクロファージ / NMR / TBP / ロイシンジッパー / 殺菌機構 / 遺伝子発現 / エンハンサー / 転写制御因子 / RNAポリメラーゼ / 受容体 / シグナル伝達 / コアクチベター / インヒビター
Research Abstract

本重点領域研究は今年度が最終年度となるので各々の研究班員は一応のまとめをすることを中心に研究を行った。審良はSTAT3遺伝子の欠失マウスを作製したところ、同型接合体で致死になることを見出した。致死は胎生期の極めて初期に観察され、原腸形成にも至らないことが判明した。また転写因子STATの特異性を決める部位がSHドメインと考えられていたが、STAT1とSTAT3のドメインスウィッチの実験からSTAT3のチロシンリン酸化部位よりさらに下流のアミノ酸も特異性の決定に関与していることを明らかにした。石井はCBPがMybのコアクチベータ-であることを明らかにすると共にショウジョウバエのcubitus interruptusのコアクチベータ-としても働き、形態形成の因子として働いていることを明らかにした。半田はカゼインキナーゼ(CKII)が転写制御に関与していることを見出して、その阻害剤DRBの作用点は転写開始前にあるが、その作用効果は転写伸長段階に現れることを見出した。これはRNAポリメラーゼIIの転写伸長活性が転写開始前に既に調節されているという新しい転写制御機構を示したものである。そのDRBの転写阻害に関わる転写制御因子(DSIF)を同定し、分離・精製した。DSIFは160と14kDaのサブユニットからなる複合体で、その部分アミノ酸配列からオリゴヌクレオチドのプライマーを作製して、RT-PCR法によってcDNAの全構造を決定した。その結果DSIFは酵母の転写因子SPT5とSPT4に相当するヒトホモローグであることが判明した。山本はGATA-1の遺伝子破壊マウスの作製に成功し、同型接合体は卵黄嚢造血細胞の成熟障害のため貧血となり胎生致死となることを明らかにした。藤井はダイオキシンなどの薬物誘導に関わるAhリセプター/Arntへテロ2量体のArntの転写活性化ドメインがCBP/P300と相互作用することを示し、この転写活性化系でもCBP/P300がコアクチベータ-として働いていることを明らかにし、さらに東大・医科研・勝木教授との共同研究でAhリセプター破壊マウスを作製し、Ahリセプターがダイオキシン等の催奇形性に関与している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] M. Ema, et al.: "Two new mambers of murine sim-homologous gene family are transcriptional repressor and show different expression patterns in mouse embryogenesis." Mol. Cell. Biol.16. 5865-5875 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M. Enari, et al.: "Sequential activation of ICE-like and CPP-like proteases during FAS-mediated apoptosis." Nature. 380. 723-726 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K. Takeda, et al.: "Esential role of STAT6 in IL-4 signalling." Nature. 380. 627-630 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] P. Dai, et al.: "CBP as a transcriptional coactivator of c-MYB." Genes & Dev.10. 528-540 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y. Shiiro, et al.: "Activation of the retinoblastoma gene expression by Bcl-3 impression for muscle cell differentiation." Oncogene. 12. 1837-1845 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H. Motohashiet al.: "Mesodermal-verus neuronal-specific expression of Maf K is elicited by different promoter." Genes Cells. 1. 223-238 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Sogawa,et al.: "Possible function of ah receptor nuclear translocator(arnt)homodimer in transcritional regulation." Proc.Natl.acad.Sci.92. 1936-1940 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T.Tanaka,et al.: "Targeted disruption of the Nf-IL6 gene dicloses its essential role in bacteria killing and tumor cytotoxicity by macrophages." Cell.80. 353-361 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Dai P.,et al.: "CBP as a transcirptional coactivator of c-Myb." Genes & Dev.(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] A.Yoshikawa,et al.: "Distrinct signal transduction through the tyrosine-containing domains of the granulocyte colony-stimulating factor receptor." EMBOJ.14. 5288-5296 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] K.Hanada,et al.: "RNA polymerase I associated factor 53 binds to the nucelolar transcription factor UBF and functions in specific rDNA transcriptiona." EMBOJ.(in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Rosmarin,A.G.,et al.: "GABP and PU.1 compete for binding ,yet cooperate to increase CD18(B2 leukocyle integrin)transcription." J.Biol.Chem.270. 23627-23633 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] M.Ema,et al.: "Dioxin-binding activities of polymorphic forms of mouse and human Ah receptors." J.Biol.Chem.269. 27337-27343 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Sogawa,et al.: "Possible function of Ah receptor nuclear translocator(Arnt)homodimer in transcriptional regulation." Proc.Natl.Acad.Sci.(in print.).

    • Related Report
      1994 Annual Research Report
  • [Publications] S.Akira,et al.: "Molecular cloning of APRF,a novel ISGF3 p91-related transcription factor involved in the gp130-mediated signiling pathway." Cell. 77. 63-71 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Kato.et al.: "Multimerization of the mouse TATA-binding protein(TBP)driven by its C-terminal domain" Nucl.Acids Res.22. 1179-1185 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Hirai,et al.: "Tax protein of human T-cell leulemia virus type I binds to the ankyrin motifs of inhibitory factor KB and induces unclear translocation of transcription factor NF-κB proteins for transcriptional activation." Proc.Natl.Acad.Sci.91. 3584-3588 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Song,et al.: "High conservation of subunit composition of RNA polymerase I(A)between yeast and mouse and the molecular cloning of mouse RNA polymerase I 40-kDa subunit RPA40." J.Biol.Chem.269. 26976-26981 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] J-I.Swada et al.: "Transcriptional activation through the tetrameric complex formation of E4TF1 subunitsa." EMBO J.(in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] D.Ma et al.: "Isolation of a cDNA encoding the largest subunit of TFIIA reveals functions imortant for activated transcription." Gens Dev.7. 2246-2257 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] H.Watanabe et al.: "cDNA cloning of transcription factor E4TF1 subunits with ETS and NOTCH motifs." Mol.Cell.Biol.13. 1385-1391 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Nakajima et al.: "Phosphorylation at threonine 235 by a ras-dependent MAP kinase is essential for transcriptional activation of NF-IL6." Proc.Natl.Acad.Sci.USA. 90. 2207-2211 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y.Nishio et al.: "A nuclear factor for interlekin6 expression(NF-IL6)and the glucocorticoid receptor synergistically activate transcription of rat α1-acid glycoprotein gene via direct protein-protein interaction." Mol.Cell.Biol.13. 1854-1862 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Matsusaka et al.: "NF-IL6 and NF-kB synergistically activate transcription of the inflammatory cytokines,IL-6 and IL-8." Proc.Natl,Acad.Sci.USA. 90. 10193-10197 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Kishimoto et al.: "Interactions of cytokines with the receptor family." Cell. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Nomura: "Negative autoregulation of c-Myb activity by homodimer formation through the leucine zipper." J.Biol.Chem.168. 21914-21923 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] I.Tanikawa et al.: "Recognition of specific DNA sequences by the c-myb proto-oncogene product:role of three repeat units in the DNA binding domain." Proc.Natl.Acad.Sci.USA. 90. 9320-9324 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] N.Sakai et al.: "Lassin:a leucine repeat-associated inhibitor of Myb." Genes Dev.(in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] E.Ishizaka-Ikeda et al.: "Signal transduction mediated by the growth hormone receptor and its chimeric molecules with the G-CSF receptor." Proc.Natl.Acad.Sci.USA. 90. 123-127 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] J.Ogasawara et al.: "Lethal effect of the anti-Fas antibody in mice." Nature. 364. 806-809 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] R.Fukunaga et al.: "Growth and differentiation signals mediated by two different regions in the cytoplasmic domain of G-CSF receptor." Cell. 74. 1079-1087 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Suda et al.: "Molecular cloning and expression of the Fas ligand,a novel member of the tumor necrosis factor family." Cell. 75. 1169-1178 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] K.Sogawa et al.: "cDNA cloning and transcriptional properties of a novel GC box-binding protein BTEB2." Nucleic Acids Res.21. 1527-1532 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] N.Watanabe et al.: "A novel cAMP-dependent regulatory region including a sequence like the cAMP-responsive element upstream of the human CYP21A2 gene." Eur.J.Biochem.214. 521-531 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Matsushita et al.: "A factor binding to the xenobiotic responsive element(XRE)of P-4501A1 gene consists of at least two helix-loop-helix proteins,Ah receptor and Arnt." J.Biol.Chem.268. 21002-21006 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] J.Fujisawa et al.: "The trans-activator Tax of human T-cell leukemia virus type 1(HTLV-1)interacts with cAMP-responsive element(CRE)binding and CRE modulator proteins that bind to the 21-base-pair enhancer of HTLV-1" Proc.Natl.Acad.Sci.USA. 90. 610-614 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Suzuki et al.: "A trans-activator Tax of human T-cell leukemia virus type 1 bimds to NF-kB p50 and serum response factor(SRF)and associates with enhancer DNAs of the NF-kB site and CArG box." Oncogene. 8. 2391-2397 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Watanabe et al.: "HTLV-1 encoded Tax in association with NF-kB precursor p105 enhancers nuclear localization of NF-kB p50 and p65 in transfected cells" Oncogene. 8. 2949-2958 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y.Maeda et al.: "Nuclear targeting of transcription factor UBF directed by both HMG boxes and acidic tail." EMBO J.11. 3695-3704 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y.Mishima et al.: "Transcription of mouse ribosomal RNA gene with inactivate extracts is activated by NAD in vitro." J.Biochem.113. 36-42 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Kermckchiev et al.: "Presence of an inhibitor of RNA polymerase I transcription in extracts from growth arrested mouse cells." Nucleic Acids Res.21. 447-453 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Wada et al.: "Methods in Enzymology" DNA affinity chromatography, ((in press))

    • Related Report
      1993 Annual Research Report

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

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