Identification of novel transcription factors involved in neuronal maintenance and degeneration.

• Project/Area Number: 23700430
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: YAMANAKA TOMOYUKI 独立行政法人理化学研究所, 脳科学総合研究センター, 研究員 (00381575)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2013)
• 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: 神経変性 / ハンチントン病 / 転写因子 / 遺伝子発現 / 神経変性疾患 / ポリグルタミン

Research Abstract

Through screening using Panomics Protein-DNA array, we identified several transcription factors (TFs) whose DNA binding activities were affected in Huntington's disease (HD) model mice brain. One of them, an E-box binding factor, interacted with mutant huntingtin aggregates. We identified ~300 downstream genes of it by ChIP-chip, and some of their expressions were affected in HD model brains. These data suggest the suppression of E-box binding factor by mutant huntingtin may be involved in some aspects of HD pathogenesis. We also examined NF-Y, another TF affected by mutant huntingtin, by analyzing its neuronal knockout mice or ChIP-chip data, and revealed its critical role in neuronal cell maintenance and degeneration.

Research Products

• [Journal Article] Large-scale RNA interference screening in mammalian cells identifies novel regulators of mutant huntingtin aggregation. (2014)
  • Author(s): Yamanaka T, Wong HK, Tosaki A, Bauer PO, Wada K, Kurosawa M, Shimogori T, Hattori N, Nukina N.
  • Journal Title: PLoS One. Volume: 9 Issue: 4 Pages: e93891-e93891
  • DOI: 10.1371/journal.pone.0093891
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] NF-Y inactivation causes atypical neurodegeneration characterized by ubiquitin and p62 accumulation and endoplasmic reticulum disorganization (2014)
  • Author(s): Yamanaka, T., Tosaki, A., Kurosawa, M., Matsumoto, G., Koike, M., Uchiyama, Y., Maity, S.N., Shimogori, T., Hattori, N. & Nukina, N.
  • Journal Title: Nat. Commun. Volume: 5 Issue: 1 Pages: 3354-3354
  • DOI: 10.1038/ncomms4354
  • Peer Reviewed
• [Journal Article] Loss of aPKCλ in differentiated neurons disrupts the polarity complex but does not induce obvious neuronal loss or disorientation in mouse brains (2013)
  • Author(s): Yamanaka T, Tosaki A, Kurosawa M, Akimoto K, Hirose T, Ohno S, Hattori N, Nukina N
  • Journal Title: PLoS One. Volume: 8(12)
  • Peer Reviewed
• [Journal Article] Loss of aPKClambda in differentiated neurons disrupts the polarity complex but does not induce obvious neuronal loss or disorientation in mouse brains (2013)
  • Author(s): Yamanaka, T., Tosaki, A., Kurosawa, M., Akimoto, K., Hirose, T., Ohno, S., Hattori, N. & Nukina, N.
  • Journal Title: PloS one Volume: 8 Issue: 12 Pages: e84036-e84036
  • DOI: 10.1371/journal.pone.0084036
  • Peer Reviewed / Open Access
• [Presentation] 転写因子 NF-Yの機能破壊はユビキチン・p62の蓄積、小胞体異常を伴う神経変性を誘導する (2014)
  • Author(s): 山中智行、戸崎麻子、黒澤大、松本弦、小池正人、内山安男、Sankar N. Maity、下郡智美、服部信孝、貫名信行
  • Organizer: 第134回日本薬学会
  • Place of Presentation: 熊本
• [Presentation] 転写因子NF-Yの機能破壊はユビキチン・p62の蓄積、小胞体異常を伴う神経変性を誘導する (2014)
  • Author(s): 山中智行、戸崎麻子、黒澤大、松本弦、小池正人、内山安男、Sankar N. Maity、下郡智美、服部信孝、貫名信行
  • Organizer: 第134回日本薬学会
  • Place of Presentation: 熊本大学
• [Presentation] Depletion of aPKC λ in mouse differentiated neurons disrupts the polarity protein complex but does not induce cell degeneration or brain structural disorganization (2013)
  • Author(s): 山中智行、戸崎麻子、黒沢大、秋本和憲、廣瀬智威、大野茂男、服部信孝、貫名信行
  • Organizer: 包括脳ネットワーク夏のワークショップ
  • Place of Presentation: 名古屋国際会議場
• [Presentation] Depletion of aPKCλ in mouse differentiated neurons disrupts the polarity protein complex but does not induce cell degeneration or brain structural disorganization (2013)
  • Author(s): 山中智行、戸崎麻子、黒沢大、秋本和憲、廣瀬智威、大野茂男、服部信孝、貫名信行
  • Organizer: 包括脳ネットワーク 夏のワークショップ 2013
  • Place of Presentation: 名古屋国際会議場
• [Presentation] Role of NF-Y transcription factor in neuronal cell maintenance and chaperone gene expression (2012)
  • Author(s): Yamanaka T, Tosaki A, Kurosawa M, Koike M, Uchiyama Y. Maity SN, Nukina N
  • Organizer: EMBO EMBL conference, September 2012
  • Place of Presentation: Heidelberg, Germany
• [Presentation] Role of NF-Y transcription factor in neuronal cell maintenance and chaperone gene expression (2012)
  • Author(s): Yamanaka T, Tosaki A, Kurosawa M, Koike M, Uchiyama Y. Maity SN, Nukina N
  • Organizer: EMBO EMBL conference
  • Place of Presentation: Heidelberg, Germany
• [Presentation] ポリグルタミン病モデル細胞を用いた凝集体測定法の確立とその応用 (2011)
  • Author(s): 山中智行, 戸崎麻子, Hon Kit Wong, Peter O Bauer, 和田浩司, 貫名信行
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜
• [Remarks] プレス発表
  • URL: http://www.juntendo.ac.jp/graduate/pdf/news06.pdf