Identification and characterization of novel complexes controling chromatin structure

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 16207009
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Molecular biology
• Research Institution: The University of Tokyo
• Principal Investigator: KATO Shigeaki The University of Tokyo, Institute of Molecular and Cellular Biosciences, Professor, 分子細胞生物学研究所, 教授 (60204468)
• Co-Investigator(Kenkyū-buntansha): TAKEYAMA Ken-ichi The University of Tokyo, Institute of Molecular and Cellular Biosciences, Lecturer, 分子細胞生物学研究所, 講師 (30323570) ; KITAGAWA Hirochika The University of Tokyo, Institute of Molecular and Cellular Biosciences, Research Associate, 分子細胞生物学研究所, 助手 (20345234) ; TAKADA Ichiro The University of Tokyo, Institute of Molecular and Cellular Biosciences, Research Associate, 分子細胞生物学研究所, 助手 (50361655)
• Project Period (FY): 2004 – 2006
• Keywords: cell type-specific complex / chromatin remodeling complex / co-legulator complex / spatio-temporal gene disraption / cre-loxP system

Research Abstract

Gene expression is controlled through chromatin remodeling and histon modifications. Such chromatin structure rearrangement is conducted by a number of nuclear complexes composed of multiple subunits. In the present study, to identify and characterize the nuclear complexes to support hormone-induced transcriptional controls by nuclear receptors, a biochemical purification of complexes associating with sex steroid hormone receptors. By such biochemical screening, we could identify several complexes containing histone modifying enzymes. One of the complex was a novel complex containing histone acetyltransferase to coactivate estrogen receptor, while another complex was a histone deacetylase to corepress estrogen and androgen receptors. Moreover, we could identify a novel ubiquitin E3 ligase to degrate sex steroid receptor proteins. Previously, we had shown that activated dioxin receptor(AhR) by ligand binding coactivates unliganded sex steroid receptors in transcriptional controls through direct receptor-receptor protein interaction (Ohtake et al., Nature, 423, 545-550, 2003). However, transrepression of liganded steroid receptors by AhR was still under investigation. By biochemical purification of a complex containing AhR and sex steroid receptors, we have demonstrated that liganded AhR is ligand- dependent E3 ubiquitin ligase to degrate steroid receptors, thereby counteracting biological actions of sex steroid hormones (Ohtake et al., Nature, 446, 562-566, 2007).

Research Products

• [Journal Article] Dioxin receptor is a ligand-dependent E3 ubiquitin ligase (2007)
  • Author(s): Ohtake, F., Baba, A., Takada, I., Okada, M., Iwasaki, K., Miki, H., Takahashi, S., Kouzmenko, A., Nohara, K., Chiba, T., Fujii-Kuriyama, Y., Kato, S.
  • Journal Title: Nature 446 Pages: 562-566
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of MicroRNAs (2007)
  • Author(s): Fukuda, T., Yamagata, K., Fujiyama, S., Matsumoto, T., Koshida, I., Yoshimura, K., Mihara, M., Nakamura.T., Akimoto, C., Yamamoto.Y., Katagiri, T., Foulds, C., Takezawa, S., Kitagawa, H., Takeyama, K., O Malley, B.W., Kato.S.
  • Journal Title: Nat. Cell Biol. 9 Pages: 604-611
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A cell cycle-dependent co-repressor for photoreceptor cell-specific nuclear receptor function (2007)
  • Author(s): Takezawa, S., Yokoyama, A., Okada, M., Fujiki, R., Iriyama, A., Yanagi, Y., Ito, H., Takada, I., Kishimoto, M., Miyajima, A., Takeyama, K., Umesono, K., Kitagawa, H., Kato, S.
  • Journal Title: EMBO J. 26 Pages: 764-774
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Dioxin receptor is a ligand-dependent E3 ubiquitin ligase (2007)
  • Author(s): Ohtake, F., Baba, A., Takada, I., Okada, M., Iwasaki, K.Miki, H., Takahashi, S., Kouzmenko, A., Nohara, K.Chiba, T., Fujii-Kuriyama, Y, Kato, S.
  • Journal Title: Nature 446 Pages: 562-566
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of MicroRNAs (2007)
  • Author(s): Fukuda, T., Yamagata, K., Fujiyama, S., Matsumoto, T., Koshida, I., Yoshimura, K., Mihara, M., Nakamura, T., Akimoto, C., Yamamoto, Y., Katagiri, T., Foulds, C., Takezawa, S., Kitagawa, H., Takeyama, K., O'Malley, B.W., Kato, S
  • Journal Title: Nat.Cell Biol. 9 Pages: 604-611
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A cell cycle-dependent co-repressor for photoreceptor cell-specific nuclear receptor function (2007)
  • Author(s): Takezawa, S., Yokoyama, A., Okada, M., Fujiki, R.Iriyama, A., Yanagi, Y, Ito, H., Takada, I., Kishimoto, M., Miyajima, A., Takeyama, K., Umesono, K.Kitagawa, H., Kato, S.
  • Journal Title: EMBO J. 26 Pages: 764-774
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Premature ovarian failure in androgen receptor-deficient mice (2006)
  • Author(s): Shiina, H., Matsumoto, T., Sato, T., Igarashi, K., Miyamoto, J., Takemasa, S., Sakari, M., Takada, I., Nakamura, T., Metzger, D., Chambon, P., Kanno, J., Yoshikawa, H., Kato.S.
  • Journal Title: Proc. Natl. Acad. Sci. USA 103 Pages: 224-229
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] lalpha, 25(OH)2D3 -induced transrepression by vitamin D receptor through E-box-type elements in the human parathyroid hormone gene promoter. (2006)
  • Author(s): Kim, M.-S., Fujiki, R., Murayama, A., Kitagawa, H., Yamamoto, K., Yamamoto, Y., Mihara, M., Takeyama, K., Kato, S.
  • Journal Title: Mol. Endocrinol. 21 Pages: 334-342
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] An hGCN5/TRRAP HAT complex coactivates BRCA1 transactivation function through histone modification (2006)
  • Author(s): Oishi, H., Kitagawa, H., Wada, O., Takezawa, S., Tora, L., Kouzu-Fujita, M., Takada, I., Yano, T., Yanagisawa, J., Kato, S.
  • Journal Title: J. Biol. Chem. 281 Pages: 20-26
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Premature ovarian failure in androgen receptor-deficient mice (2006)
  • Author(s): Shiina H, Matsumoto, T., Sato, T., Igarashi, K.Miyamoto, J., Takemasa, S., Sakari, M., Takada, I.Nakamura, T., Metzger, D., Chambon, P., Kanno, J.Yoshikawa, H., Kato, S.
  • Journal Title: Proc.Natl.Acad.Sci.USA 103 Pages: 224-229
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] lalpha, 25(OH)2D3 -induced transrepression by vitamin D receptor through E-box-type elements in the human parathyroid hormone gene promoter (2006)
  • Author(s): Kim M.-S., Fujiki, R., Murayama, A., Kitagawa, H., Yamamoto, K., Yamamoto, Y., Mihara, M., Takeyama, K., Kato, S.
  • Journal Title: MoL Endocrinol. 21 Pages: 334-342
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] An hGCN5/TRRAP HAT complex coactivates BRCA1 transactivation function through histone modification (2006)
  • Author(s): Oishi H, Kitagawa, H., Wada, O., Takezawa, S., Tora, L., Kouzu-Fujita, M., Takada, I., Yano, T., Yanagisawa, J., Kato, S.
  • Journal Title: J.Biol.Chem. 281 Pages: 20-26
  • Description: 「研究成果報告書概要(欧文)」より