Function of Z-DNA structure in Nrf2-dependent gene activation

• Project/Area Number: 23790319
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Hirosaki University
• Principal Investigator: MARUYAMA Atsushi 弘前大学, 医学(系)研究科(研究院), 助教 (10431438)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 酸化ストレス / 転写制御 / Nrf2 / Z-DNA / ヘムオキシゲナーゼ‐1 / HO-1 / 転写調節

Research Abstract

Left-handed double helix of DNA, called Z-DNA, is an alternative structure of DNA and appears to have many diverse roles in nuclear processes such as transcriptional regulation and nucleosome positioning. In this study, I have developed a method for in vivo detection of Z-DNA formation and show Nrf2 activation is associated with Z-DNA formation in the HO-1 gene promoter. The results implicate Nrf2-dependent Z-DNA formation in HO-1 gene transcriptional activation and suggestthe involvement of BRG1 in Z-DNA formation. Human HO-1 gene promoter might be a good model system to understand Z-DNA formation and how Z-DNA forming sequences regulate geneexpression.

Research Products

• [Journal Article] Nrf2 activation is associated with Z-DNA formation in the human HO-1 promoter (2013)
  • Author(s): Maruyama A, Mimura J, Harada N, Itoh K
  • Journal Title: Nucleic Acids Res Volume: (in press) Issue: 10 Pages: 12-12
  • DOI: 10.1093/nar/gkt243
  • Peer Reviewed
• [Journal Article] Keap1 is localized in neuronal and glial cytoplasmic inclusions in various neurodegenerative diseases (2013)
  • Author(s): Tanji K, Maruyama A, Odagiri S, Mori F, Itoh K, Kakita A, Takahashi H, Wakabayashi K
  • Journal Title: J Neuropathol Exp Neurol Volume: 72 Issue: 1 Pages: 18-28
  • DOI: 10.1097/nen.0b013e31827b5713
  • Peer Reviewed
• [Journal Article] Alteration of autophagosomal proteins in the brain of multiple system atrophy. (2012)
  • Author(s): Tanji K, Odagiri S, Maruyama A, Mori F, Kakita A, Takahashi H, Wakabayashi K.
  • Journal Title: Neurobiol Dis Volume: 49C Pages: 190-198
  • DOI: 10.1016/j.nbd.2012.08.017
  • Peer Reviewed
• [Journal Article] Nrf2 in bone marrow-derived cells positively contributes to the advanced stage of atherosclerotic plaque formation (2012)
  • Author(s): Harada N, Ito K, Hosoya T, Mimura J, Maruyama A, Noguchi N, Yagami KI, Morito N, Takahashi S, Maher JM, Yamamoto M, Itoh K
  • Journal Title: Free Radic Biol Med Volume: 53 Issue: 12 Pages: 2256-2262
  • DOI: 10.1016/j.freeradbiomed.2012.10.001
  • Peer Reviewed
• [Journal Article] Nrf2 regulates NGF mRNA induction by carnosic acid in T98G glioblastoma cells and normal human astrocytes (2011)
  • Author(s): Mimura J, Kosaka K, Maruyama A, Satoh T, Harada N, Yoshida H, Satoh K, Yamamoto M, Itoh K
  • Journal Title: J Biochem Volume: 150 Issue: 2 Pages: 209-217
  • DOI: 10.1093/jb/mvr065
  • NAID: 10030587033
  • Peer Reviewed
• [Journal Article] The novel NRF2-interacting factor KAP1 regulates the susceptibility to oxidative stress by promoting NRF2-mediated cytoprotective response (2011)
  • Author(s): Maruyama A, Nishikawa K, Kawatani Y, Mimura J, Hosoya T, Harada N, Yamamato M, Itoh K
  • Journal Title: Biechem J Volume: 436 Issue: 2 Pages: 387-397
  • DOI: 10.1042/bj20101748
  • Peer Reviewed
• [Journal Article] Nrf2 regulates ferroportin 1-mediated iron efflux and counteracts lipopolysaccharide-induced ferroportin-1 mRNA suppression in macrophages (2011)
  • Author(s): Harada N, Kanayama M, Maruyama A, Yoshida A, Tazumi K, Hosoya T, Mimura J, Toki T, Maher JM, Yamamoto M, Itoh K
  • Journal Title: Arch Biochem Biophys Volume: 508 Issue: 1 Pages: 101-109
  • DOI: 10.1016/j.abb.2011.02.001
  • Peer Reviewed
• [Journal Article] Nrf2 regulates ferroportin 1-mediated iron efflux and counteracts lipopolysaccharide-induced ferroportin 1 mRNA suppression in macrophages. (2011)
  • Author(s): Harada N*, Kanayama M*, Maruyama A*, Yoshida A, Tazumi K, Hosoya T, Mimura J, Toki T, Maher JM, Yamamoto M, Itoh K.*: equal contribution.
  • Journal Title: Arch. Biochem. Biophys. Volume: 508 Pages: 101-109
  • Peer Reviewed
• [Journal Article] The novel NRF2-interacting factor KAP1 regulates susceptibility to oxidative stress by promoting the NRF2-mediated cytoprotective response. (2011)
  • Author(s): Maruyama A, Nishikawa K, Kawatani Y, Mimura J, Hosoya T, Harada N, Yamamoto M, Itoh K.
  • Journal Title: Biochem. J. Volume: 436 Pages: 387-397
  • Peer Reviewed
• [Journal Article] Nrf2 regulates NGF mRNA induction by carnosic acid in T98G glioblastoma cells and normal human astrocytes. (2011)
  • Author(s): Mimura J, Kosaka K, Maruyama A, Satoh T, Harada N, Yoshida H, Satoh K, Yamamoto M, Itoh K.
  • Journal Title: J. Biochem. (Tokyo) Volume: 150 Pages: 209-217
  • NAID: 10030587033
  • Peer Reviewed
• [Presentation] 酸化ストレス誘導性遺伝子HO-1発現を制御するnon-codingRNAsの解析 (2012)
  • Author(s): 丸山敦史、伊東健
  • Organizer: 第85回日本生化学会大会(ポスター発表)
  • Place of Presentation: 福岡
• [Presentation] Nrf2 induces the Z-DNA formation in the human HO-1 promoter. 7th International Meeting on Heme Oxygenases & Related Enzymes (Poster presentation) (2012)
  • Author(s): Maruyama A, Itoh K
  • Organizer: University of Edinburgh
  • Place of Presentation: Edinburgh (英国)
• [Presentation] Nrf2 induces the Z-DNA formation in the human HO-1 promoter. (2012)
  • Author(s): Maruyama Atsushi
  • Organizer: 7th International Meeting on Heme Oxygenases & Related Enzymes
  • Place of Presentation: University of Edinburgh, Edinburgh (英国）
• [Presentation] 酸化ストレス誘導性遺伝子HO-1発現を制御するnon-coding RNAsの解析 (2012)
  • Author(s): 丸山敦史
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡
• [Presentation] Nrf2 enhances PolII andBRG1 binding to the human HO-1 promoter (2011)
  • Author(s): Maruyama A, Itoh K
  • Organizer: 第34回日本分子生物学会年会(ポスター発表)
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-15
• [Presentation] Nrf2なヒトHO-1遺伝子発現活性化機構の解析 (2011)
  • Author(s): 丸山敦史、伊東健
  • Organizer: 第77回日本生化学会東北支部例会(口頭発表)
  • Place of Presentation: 仙台
  • Year and Date: 2011-07-23
• [Presentation] Nrf2なヒトHO-1遺伝子発現活性化機構の解析 (2011)
  • Author(s): 丸山敦史，伊東健
  • Organizer: 第77回日本生化学会 東北支部例会
  • Place of Presentation: 仙台
• [Presentation] Nrf2 enhances PolII and BRG1 binding to the human HO-1 promoter. (2011)
  • Author(s): Atsushi Maruyama， Ken Itoh
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Book] 実験医学増刊、活性酸素・ガス状分子による恒常性制御と疾患 (2012)
  • Author(s): 丸山敦史、伊東健
  • Publisher: 羊土社
• [Book] 実験医学増刊、活性酸素・ガス状分子による恒常性制御と疾患 (2012)
  • Author(s): 丸山敦史
  • Total Pages: 8
  • Publisher: 羊土社
• [Remarks] 弘前大学大学院医学研究科附属高度先進医学研究センター分子生体防御学講座
  • URL: http://www.med.hirosaki-u.ac.jp~/admed/department/index.html
• [Remarks] 弘前大学大学院医学研究科附属高度先進医学研究センター分子生体防御学講座
  • URL: http://www.med.hirosaki-u.ac.jp/~admed/department/index.html