A novel role of oncogenic RAS in gene silencing

2013 Fiscal Year Final Research Report

• Project/Area Number: 24700951
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Carcinogenesis
• Research Institution: Tohoku University
• Principal Investigator: FUNAYAMA Ryo 東北大学, 医学(系)研究科(研究院), 助教 (20452295)
• Research Collaborator: NAGASHIMA Takeshi 東北大学, 大学院医学系研究科, 助教 (80443000) ; HOSOGANE Masaki 東北大学, 大学院医学系研究科, 大学院生
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: エピジェネティクス / ヒストン / 発がん / RAS / 転写 / サイレンシング / ｓｈRNA / スクリーニング

Research Abstract

RAS-MAPK signaling regulates cell growth and survival. It is abnormally activated in cancer cells and represses transcription of tumor-suppressive genes to enhance tumorigenesis of the cells. In this study, I investigated the molecular mechanism of RAS-mediated transcriptional repression. RAS-MAPK signaling increases the amount of a histone modification in transcriptionally repressed genes. The alteration of the histone modification occurs after alteration of transcription, suggesting that the histone modification functions to maintain transcriptionally repressed state. Furthermore, I identified three chromatin proteins, which are required for transcriptional repression.

Research Products

• [Journal Article] Ras-induced changes in H3K27me3 occur after those in transcriptional activity (2013)
  • Author(s): Hosogane, M., Funayama, R., Nishida, Y., Nagashima, T. & Nakayama, K.
  • Journal Title: PLoS genetics Volume: 9 Pages: e1003698
  • DOI: 10.1371/journal.pgen.1003698
  • Peer Reviewed
• [Journal Article] Distinct MicroRNAs Expression Profile in Primary Biliary Cirrhosis and Evaluation of miR 505-3p and miR197-3p as Novel Biomarkers (2013)
  • Author(s): Ninomiya, M., Kondo, Y., Funayama, R., Nagashima, T., Kogure, T., et al.
  • Journal Title: PloS one Volume: 8 Pages: e66086
  • DOI: 10.1371/journal.pone.0066086
  • Peer Reviewed
• [Journal Article] ChIP-seq解析をはじめる人のために-ENCODEのChIP-seq解析ガイドライン (2013)
  • Author(s): 舟山亮
  • Journal Title: 実験医学増刊 Volume: 31 Pages: 201-205
  • URL: https://www.yodosha.co.jp/jikkenigaku/book/9784758103282/index.html
• [Journal Article] Illumina社製シークエンサーの特徴と可能性 (2013)
  • Author(s): 中山啓子, 舟山亮
  • Journal Title: 肝胆膵 Volume: 67 Pages: 25-33
  • URL: http://arcmedium.co.jp/publication02.php?a=201307
• [Journal Article] Use of illumina deep sequencing technology to differentiate hepatitis C virus variants (2012)
  • Author(s): Ninomiya, M., Ueno, Y., Funayama, R., Nagashima, T., Nishida, Y., et al.
  • Journal Title: J Clin Microbiol Volume: 50 Pages: 857-866
  • DOI: 10.1128/JCM.05715-11
  • Peer Reviewed
• [Journal Article] 高感度に多型を検出するためのエキソーム・シークエンシング (2012)
  • Author(s): 舟山亮, 長嶋剛史, 中山啓子
  • Journal Title: 実験医学 Volume: 30 Pages: 629-34
  • URL: https://www.yodosha.co.jp/jikkenigaku/book/9784758100816/index.html
• [Presentation] がん遺伝子Rasによる転写変化後のH3K27me3修飾変化 (2013)
  • Author(s): 細金正樹, 舟山亮, 西田有一郎, 長嶋剛史, 中山啓子
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2013-12-03
• [Presentation] Ras-MAPKシグナルを介したFas遺伝子の転写抑制機構の解析 (2013)
  • Author(s): 舟山亮, 細金正樹, 長嶋剛史, 中山啓子
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2013-12-03
• [Presentation] RAS-MAPKシグナルによる遺伝子発現制御とエピゲノム変化 (2013)
  • Author(s): 舟山亮
  • Organizer: 疾患エピゲノムコアセンター第1回ミニシンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2013-10-26
• [Presentation] Comprehensive Analysis of Ras-Mediated Alternative Splicing (2013)
  • Author(s): Matsushima, W., Funayama, R., Nagashima, T., Nakayama, K.
  • Organizer: NIH-Tohoku University-JSPS Symposium
  • Place of Presentation: 仙台
  • Year and Date: 2013-05-10
• [Presentation] Change of Trimethylation of H3K27 Occurs after Ras-mediated Transcriptional Regulation (2013)
  • Author(s): Nakayama, K., Hosogane, M., Funayama, R., Nagashima, T.
  • Organizer: NIH-Tohoku University-JSPS Symposium
  • Place of Presentation: 仙台
  • Year and Date: 2013-05-09
• [Presentation] がん遺伝子Rasによる転写制御後にH3K27me3修飾変化が誘起される (2012)
  • Author(s): 細金正樹, 舟山亮, 西田有一郎, 長嶋剛史, 中山啓子
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-14
• [Presentation] shRNAライブラリのスクリーニングによる遺伝子サイレンシング機構の解析 (2012)
  • Author(s): 舟山亮, 細金正樹, 長嶋剛史, 中山啓子
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-13
• [Presentation] RASシグナルによる選択的スプライシング変化の網羅的解析 (2012)
  • Author(s): 松島和洋, 舟山亮, 長嶋剛史, 中山啓子
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-12
• [Presentation] Comprehensive analysis of altemative splicing by next-generation sequencer (2012)
  • Author(s): Matsushima, W., Funayama, R., Nagashima, T., Nakayama, K.
  • Organizer: Winter Camp of GCOE 2012, Tohoku University Global COE for Conquest of Signal Transduction Diseases with"Network Medicine"
  • Place of Presentation: 仙台
  • Year and Date: 2012-02-04
• [Presentation] Change of trimethylation of H3K27 occurs after Ras-mediated transcriptional regulation (2012)
  • Author(s): Hosogane, M., Funayama, R., Nishida, Y., Nagashima, T., Nakayama, K.
  • Organizer: Winter Camp of GCOE 2012, Tohoku University Global COE for Conquest of Signal Transduction Diseases with"Network Medicine"
  • Place of Presentation: 仙台
  • Year and Date: 2012-02-04
• [Remarks]
  • URL: http://www.devgen.med.tohoku.ac.jp/index.html