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2001 Fiscal Year Final Research Report Summary

Analysis of biological function of regulatory network composed of bZip transcription factors

Research Project

Project/Area Number 12308036
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Molecular biology
Research InstitutionUniversity of Tsukuba

Principal Investigator

YAMAMOTO Masayuki  University of Tsukuba, Institute of Basic Medical Sciences, Professor, 基礎医学系, 教授 (50166823)

Co-Investigator(Kenkyū-buntansha) MOTOHASHI Hozumi  University of Tsukuba, Institute of Basic Medical Sciences, Assistant Professor, 基礎医学系, 講師 (00282351)
Project Period (FY) 2000 – 2001
KeywordsbZip transcription factors / gene targeting / transcription / megakaryocytes / neurodegeneration / gene regulatory network
Research Abstract

Searching for target genes regulated by bZip network.
Proplatelet formation, which is regarded as a major pathway of platelet production, is severely impaired in megakaryocytes obtained from mafG-/-::mafK+/- mutant bone marrow. In order to identify the target genes of small Mafproteins which are important for platelet production, we subtracted CDNA pool of mafG-/-::mafK+/- megakaryocytes from that of wild type megakaryocytes. CDNA clones coding cytoskeletal proteins, such as actin and tubulin, were obtained. One clone obtained from the subtraction, #325, encoded novel unknown protein. Expression level of #325 was high in megakaryocytes but low in erythoid cells. This expression profile suggested that #325 plays an important role in megakaryocytic differentiation, maturation and platelet production.
Analysis of bZip network function in neuronal cells.
MafG-/-::mafK+/- compound mice display severe motor disorder which becomes apparent at two months after birth. This sign resembled hereditary hyperekplexia in human, which is caused by functional insufficiency of glycine receptor. When we examined the expression levels of glycine reseptor subunit genes, both alpha and beta subunits were reduced. This result indicated that glycine receptor subunit genes are regulated through MARE directly or indirectly.
Effect of small Maf proteins to subcellular localization of Bach proteins.
Binding activity to MARE in the brain nuclear extract from mafG-/-::mafK+/- mice was examined by EGMSA, and we found that a shifted band comnosed of Bach/small Maf heterodimers is remarkably reduced in intensity. Interestingly, nuclear localization that Bach proteins was imuuHcu in mafG-/-::mafK;/- brain. It was concluded that small Maf proteins promote the nuclear localization of Bach, which depends on bZip structure of small Maf.

  • Research Products

    (59 results)

All Other

All Publications (59 results)

  • [Publications] Enomoto, A. et al.: "High sensitivity of Nrf2 knockout mice to acetoaminophen hepatotoxicity associated with decreased expression of ARE-regulated drug metabolizing enzyme and antioxidant genes"Toxicol. Sci.. 59. 169-177 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tabata, M. et al.: "Stimulation of GATA-2 as a mechanism of hydrogen peroxide suppression in hypoxia-induced erythropoietin gene expression"J. Cell. Physiol.. 186. 260-267 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ramos-Gomez, M.: "Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice"Proc. Nati. Acad. Sci. USA. 98. 3410-3415 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kwak.M-K., et al.: "Role of Transcription factor Nrf2 in the induction of hepatic phase 2 and antioxidative enzymes in vivo by the cancer chemopreventive agent, 3H-1, 2-dithiole-3-thione"Mol. Med.. 7. 135-145 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanezaki, R., et al.: "Transcription factor BACHL is recruited to nucleus by its novel alternative spliced isoform expressed in testis"J. Biol. Chem.. 276. 7278-7284 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kobayashi, M., et al.: "The homeobox protein Six3 interacts with the Groucho corepressor and acts as a transcriptional repressor in eye and forebrain formation"Dev. Biol.. 232. 315-326 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hosoya, T. et al.: "Defective development of secretary neurons in the hypothalamus of Arnt2-knockout mice"Genes Cells. 6. 361-374 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Umetani, M.: "Function of GATA transcription factors in the induction of endothelial VCAM-1 by TNF-α"Arterioscler. Thromb. Vasc. Biol.. 21. 917-922 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kobayashi, M. et al.: "Positive regulation by GATA-1 of GATA-1 gene hematopoietic regulatory domain in zebrafish embryos in vivo"Development. 128. 2341-2350 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kim, Y-C. et al.: "Hemin-induced activation of the Thioredoxin gene by Nrf2 : a differential regulation of the antioxidant responsive element (ARE) by switch of its binding factors"J. Biol. Chem.. 276. 18399-18406 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogawa, K.: "Heme mediates de-repression of Maf recognition element through direct binding to transcription factor Bach1"EMBO J.. 20. 2835-2843 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoh, K.: "Nrf2 deficient mouse : a novel model for lupus nephritis"Kindney Int.. 60. 1343-1353 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Katho, Y. et al.: "Two domains of Nrf2 cooperatively bind CBP (CREB binding protein) and synergistically activate transcription"Genes Cells. 6. 857-868 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimizu, R. et al.: "In vivo requirements for functional GATA-1, domains during primitive and definitive erythropoiesis"EMBO J.. 20. 5250-5260 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sun, J. et al.: "The promoter of mouse transcription repress is bach1 is regulated by Sp1 and transactivated by Bach1"J. Biochem.. 130. 385-392 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] McMahon, M. et al.: "The Cap'n' Collar basic leucine zipper transcription factor Nrf2 controls both constitutive and inducible expression of intestinal detoxification and glutathione biosynthetic enzymes"Cancer Res.. 61. 3299-3307 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Imagawa, S. et al.: "Levels of vascular endothelial growth factor are elevated in patients with obstructive sleep apnea-hypopnea syndrome"Blood. 98. 1255-1257 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kwak, M.K. et al.: "Role of phase 2 enzyme induction in chemoprotection by dithiolethiones"Mutat Res.. 481. 305-315 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoh, K. et al.: "Transgenic overexpression of MafK suppresses T cell proliferation and function in vivo"Genes Cells. 6. 1055-1066 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujimoto, T. et al.: "Stepwise divergence of primitive and definitive hematopoietic and endothelial cell lineages"Genes Cells. 6. 1113-1127 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Aoki, Y. et al.: "Accelerated DNA adducts formation in the lung of the Nrf knockout mouse exposed to diesel exhaust"Toxicol. Appl. Pharmacol. 173. 154-160 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Cho, H.Y. et al.: "Linkage analysis of susceptibility to hyperoxic lung injury : role of the Nrf as a candidate gene"Am. J. Res. Cell Mol. Biol.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Morimitsu, Y.: "A sulforaphane analogue that potentially activates the Nrf2-dependent detoxification pathway"J. Biol. Chem.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kirito, K. et al.: "A functional role of Stat3 in in vivo megakaryopoiesis"Blood. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kusunoki, H. et al.: "Solution structure of the DNA-binding domain of MafG"Nature Str. Biol.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kwak, M.K. et al.: "Regulation of the expression of Nrf2 transcription factor by cancer chemopreventive agents through antioxidant response element (ARE)-like sequences in its proximal promoter region"Mol. Cell. Biol.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ueno, Y. et al.: "Elimination of Pasteurella pneumotropica from a Contaminated Mouse Colony by Oral Administration of Enrofloxacin"Exp. Animals. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山本雅之編: "「遺伝子の構造と機能」シリーズ・バイオサイエンスの新世紀"日本生化学会編集, 共立出版. 178 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 勝岡史城, 山本雅之: "新臨床医のための分子医学シリーズ/造血幹細胞研究のいまと臨床応用「遺伝子操作マウスを用いた血液疾患モデルの作製」"羊土社. (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中島修, 山本雅之: "Annal Review 血液2002「X染色体連鎖型鉄芽球性貧血モデルおよび鉄代謝異常関連遺伝子改変動物の分子生物学的解析」"中外医学社(印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 鈴木教郎, 山本雅之: "造血幹細胞:基礎から遺伝子医療・再生医療へ「造血幹細胞の転写調節機構」"中外医学社(印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishimura, S., Takahashi, S., Kuroha., T., Suwabe, N., Nagasawa, T., Trainor, C., Yamamoto, M.: "A GATA box in the GATA-1 gene hematopoietic enhancer is critical element in the network of GATA factors and sites that regulate this gene"Mol. Cell. Biol.. 20. 713-723 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Pan, X., Minegishi, N., Harigae, R, Yamagiwa, H., Minegishi, M., Akine, Y., Yamamoto, M.: "Identification of human GATA-2 gene distal IS exon and its expression in hematopoietic stem cell fractions."J. Biochem. 127. 105-112 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kobayashi, A., Yamagiwa, R, Hoshino, H., Muto, A., Sato, K., Morita, M., Hayashi, N., Yamamoto, M., Igarashi, K.: "A combinatorial code for gene expression generated by transcription factor Bach2 and MAZR (MAZ-related factor) through BTB/ POZ domain."Mol. Cell. Biol.. 20. 1733-1746 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Onodera, K., Shavit, J.A., Motohashi, H., Yamamoto. M., Engel JD.: "Perinatal synthetic lethality and hematopoietic detects in compound mafG::mafK mutant mice"EMBO J. 19. 1335-1345 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katsuoka, E, Motohashi, H., Onodera, K., Suwabe, N., Engel J. D., Yamamoto, M.: "One enhancer mediates mafK transcriptional activation in both hematopoietic and cardiac muscle cells."EMBO J. 19. 2980-2991 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishii, T., Itoh, K., Akasaka, J., Yanagawa, T., Takahashi, S., Yoshida, H., Bannai, S., Yamamoto, M.: "Induction of murine intestinal and hepatic peroxiredoxin MSP23 by dietary butylated hydroxyanisole."Carcinogenesis. 21. 1013-1016 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hoshino, H., Kobayashi, A., Yoshida, M., Ovake, T., Motohashi, H., Hayashi, N., Yamamoto, M., Igarashi, K.: "Oxidative stress abolishes leptomycine B-sensitive nuclear export of transcription represser Bach2 that counteracts activation of Maf recognition element"J. Biol. Chem.. 275. 15370-15376 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishii, T., Itok K., Takahashi, S., Satb, H., Yanagawa, T., Katoh, Y., Bannai, S., Yamamoto, M.: "Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages"J. Biol. Chem.. 275. 16023-16029 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi, S., Shimizu, R., Kuroha, T., Yoh, K., Suwabe, R, Ohta, J., Nishimura, S. Limu, K-C., Engel, J.D., Yamamoto, M.: "GATA factor transgenes under GATA-1 locus control rescue germ line GATA-1 mutant deficiencies"Blood. 96. 910-916 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hayes, J. D., Chanas, S. A., Henderson, C. J., McMahon, M., Sun, C., Moffat, G. J., Wolf, C. R., Yamamoto, M.: "The Nrf2 transcription factor contributes both to the basal expression of glutathione S-transferases in mouse liver and to their induction by the chemopreventive synthetic antioxidants, butylated hydroxyanisole and ethoxyquin."Biochem. Soc. Trans.. 28. 33-41 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Motonasni, H., Katsuoka, F., Shavit, J., Engel. J. D., Yamamoto, M.: "Positive or negative MARE-dependent transcriptional regulation determined by the abundance of small Maf proteins"Cell. 103. 865-875 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kobayashi, M., Osanai, H., Kawakami, K., Yamamoto, M.: "Expression of three zebrafish Six3 genes in cranial sensory placodes and the developing somites"Mech. Dev.. 98. 151-155 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Enomoto, A., Itoh, K., Nagayoshi, E., Hamta, J., Kimura, T., O'Connor, T., Harada, T., Yamamoto, M.: "High sensitivity of Nrf2 knockout mice to acetoaminophen hepatotoxicitv associated with decreased expression of ARE-regulated drug metabolizing enzyme and antioxidant genes"Toxicol. Sci.. 59. 169-177 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ramos-Gomez, M., Kvyak, M-K., Dolan, P. M., Itoh, K., Yamamoto, M., Talalay, P., Kensler, T. W.: "Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nr」2 transcription factor-deficient mice"Proc. Natl. Acad. Sci.. 98. 3410-3415 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kwak, M-K, Itoh, K., Yamamoto, M., Suffer, T. R., Kensler, T. W.: "Role of Transcription factor Nrf2 in the induction of hepatic phase 2 and antioxidative enzymes in vivo by the cancer chemopreventive agent, 3H-1, 2-dithiole-3-thione"Mol. Med.. 7. 135-145 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kobayashi, M., Nishikawa, K., Suzuki, T., Yamamoto, M.: "The homeobox protein Six3 interacts with the Groucho corepressor and acts as a transcriptional repressor in eye and forebrain formation"Dev. Biol.. 232. 315-326 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hosoya, T., Oda, Y, Takahashi, S., Morita, M., Kawauchi, S., Ema, M., Yamamoto, M., Fujii-Kuriyama, Y.: "Defective development of secretary neurons in the hypothalamus of Arnt2-knockout mice"Genes Cells. 6. 361-374 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kobayashi, M., Nishikawa, K., Yamamoto, M.: "Positive regulation by GATA-1 of GATA-1 gene hematopoietic regulatory domain in zebrafish embryos in vivo"Development. 128. 2341-2350 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Aoki, Y, Sato, H., Nishimura, N., Takahashi, S., Itoh, K., Yamamoto, M.: "Accelerated DNA adducts formation in the lung of the Nif2 knockout mouse exposed to diesel exhaust"Toxicol. Appl. Pharmacol.. 173. 154-160 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoh, K., Itoh, K., Enomoto, A., Hirayama, A., Yamaguchi, N., Kobayashi, M., Morito, N., Koyama, A., Yamamoto, M., Takahashi, S.: "Nrf2 deficient mouse : a novel model for lupus nephritis"Kidney Int.. 60. 1343-1353 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katoh, Y, Itoh, K., Yoshida, E., Miyagishi, M., Fukamizu., A., Yamamoto, M.: "Two domains of Nrf2 cooperatively bind CBP (CREB binding protein) and synergistically activate transcription"Genes Cells. 6. 857-868 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimizu, R., Takahashi, S., Ohneda, K., Engel, I D., Yamamoto, M.: "In vivo requirements for functional GATA-1 domains during primitive and definitive erythropoiesis"EMBO J.. 20. 5250-5260 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] McMahon, M., Itoh, K., Yamamoto, M., Chanas, S. A., Henderson, C. J., McLellan, L. I., Wolf, C. R., Cavin, C., Hayes, J. D.: "The Cap' n' Collar basic leucine zipper transcription factor Nrf2 controls both constitutive and inducible expression of intestinal detoxification and glutathione biosynthetic enzymes"Cancer Res.. 61. 3299-3307 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kwak, M. K., Egner, P. A., Dolan, P. M., Ramos-Gomez, M., Groopman, J. D., Itoh, K., Yamamoto, M., Kensler, T. W.: "Role of phase 2 enzyme induction in chemoprotection by dithiolethiones"Mutat Rels.. 481. 305-315 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoh, K., Sugawara, T., Motohashi, H., Takahama, Y, Koyama, A., Yamamoto, M., Takahashi, S.: "Transgenic overexpression of MafiC suppresses T cell proliferation and function in vivo"Genes Cells. 6. 1055-1066 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Cho, H. Y., Jedlika, A. E., Reddy, S. P. M., Zhang, L. Y., Yamamoto, M.,Kensler, T. W., Kleeberger, S. R.: "Linkage analysis of susceptibility to hyperoxic lung injury : role of Nrf2 as a candidate gene"Am. J. Res. Cell Mol. Biol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kusunoki, H., Motohashi, H., Katsuoka, R, Morohashi, A., Yamamoto, M., Tanaka, T.: "Solution structure of the DNA-binding domain of MafG"Nature Str. Biol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kwak, M. K., Itoh, K., Yamamoto, M, Kensler, T.: "Regulation of the expression of Nrf2 transcription factor by cancer chemopreventive agents through antioxidant response element (ARE)-like sequences in its proximal promoter region"Mol. Cell. Biol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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