Elucidation of nucleosome structural changes based on histone modifications

• Project/Area Number: 24370052
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Horikoshi Masami 東京大学, 分子細胞生物学研究所, 准教授 (70242089)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000); Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2012: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
• Keywords: ヒストンシャペロン / ヌクレオソーム / 化学修飾 / 構造変換 / ヌクレオソームアセンブリー / ヌクレオソームディスアセンブリー / ヒストン / ヒストンバリアント

Outline of Final Research Achievements

We used a histone-GLibrary that encompasses the nucleosomal DNA entry/exit site to show that six residues form a surface on the structured nucleosome core and regulate H3-K36me3. We also found an interaction between Jhd2 and H2A. Two H2A residues serve as a binding site for Jhd2 and mediate its chromatin association and H3K4 demethylase functions. We described a method to discriminate between the functions of a common subunit in different multisubunit complexes. A common subunit in a multisubunit complex is genetically fused to a subunit that is specific to that complex and point mutated. The resulting phenotype(s) identify the specific function(s) of the subunit in that complex only. We proposed an innovative concept for evolutionary analysis that does not require an outer group. This approach utilizes the similarity in intramolecular direct repeats as an evolutionary measure revealing the degree of similarity between the present offspring genes and their ancestors.

Research Products

• [Journal Article] Interaction of the Jhd2 H3K4 demethylase with chromatin is promoted by histone H2A surfaces and restricted by H2B ubiquitylation (2015)
  • Author(s): F.Huang, S.Ramakrishnan, C.Pflueger, T.J.Parnell, M.M.Kasten, S.L.Currie, N.Bhachech, M.Horikoshi, B.J.Graves, S.Bhaskara, B.R.Cairns & M.B.Chandrasekharan
  • Journal Title: J.Biol.Chem. Volume: 290 Issue: 48 Pages: 28760-28777
  • DOI: 10.1074/jbc.m115.693085
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Roles of common subunits within distinct multisubunit complexes (2014)
  • Author(s): Y. Nakabayashi, S. Kawashima, T. Enomoto, M. Seki, M. Horikoshi
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 111 Issue: 2 Pages: 699-704
  • DOI: 10.1073/pnas.1316433111
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Histone acetylation: From code to web and router via intrinsically disordered regions (2013)
  • Author(s): M.Horikoshi
  • Journal Title: Curr. Pharm. Design Volume: 19 Issue: 28 Pages: 5019-5042
  • DOI: 10.2174/1381612811319280002
  • Peer Reviewed
• [Journal Article] Nucleosome surface containing nucleosomal DNA entry/exit site regulates H3-K36me3 via DNA entry/exit site regulates H3-K36me3 via (2012)
  • Author(s): H.Endo, Y.Nakabayashi, S.Kawashima, T.Enomoto, M.Seki & M.Horikoshi
  • Journal Title: Genes Cells Volume: 17 Issue: 1 Pages: 65-81
  • DOI: 10.1111/j.1365-2443.2011.01573.x
  • Peer Reviewed
• [Presentation] Roles of residues of common subunits within major and variant nucleosome complexesUncovering ancient transcription systems with a novel evolutionary indicator (2016)
  • Author(s): 堀越 正美
  • Organizer: Keystone Symposia- Chromatin and Epigenetics
  • Place of Presentation: ウィスラー（カナダ ブリティッシュコロンビア州）
  • Year and Date: 2016-03-20
  • Int'l Joint Research / Invited
• [Presentation] Roles of residues of common subunits within major and variant nucleosome complexes (2016)
  • Author(s): 堀越 正美
  • Organizer: Keystone Symposia-Enhancer Malfunction in CancerJoint meeting:Noncoding RNAs in Health and Disease
  • Place of Presentation: サンタフェ（米国 ニューメキシコ州）
  • Year and Date: 2016-02-21
  • Int'l Joint Research
• [Presentation] 頑強性・脆弱性：要素からシステムまでの横断的理解 (2015)
  • Author(s): 堀越 正美
  • Organizer: BMB2015（第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会）
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] Roles of modification residues within H2A- and Htz1-containing nucleosome complexes (2015)
  • Author(s): 堀越 正美
  • Organizer: Keystone Symposia-Epigenomics
  • Place of Presentation: キーストーン（米国コロラド州）
  • Year and Date: 2015-03-29
  • Int'l Joint Research
• [Presentation] Roles of modification residues within H2A- and Htz1-containing nucleosome complexes (2015)
  • Author(s): 堀越 正美
  • Organizer: Keystone Symposia-Epigenetics and Cancer
  • Place of Presentation: キーストーン（米国コロラド州）
  • Year and Date: 2015-01-25
  • Int'l Joint Research
• [Presentation] 複数のマルチサブユニット複合体に共通に存在するサブユニットの機能解析 (2014)
  • Author(s): 堀越 正美
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-25
  • Invited
• [Presentation] Roles of common subunits within distinct multi-subunit complexes (2014)
  • Author(s): 堀越 正美
  • Organizer: CSHL Meeting- Epigenetics & Chromatin
  • Place of Presentation: コールド・スプリング・ハーバー（米国ニューヨーク州）
  • Year and Date: 2014-09-09
  • Int'l Joint Research
• [Presentation] 複数のマルチサブユニット複合体に共通に存在するサブユニットの機能解析 (2014)
  • Author(s): 堀越 正美
  • Organizer: 第14回日本蛋白質科学会年会
  • Place of Presentation: ワークピア横浜及び横浜産貿ホール マリネリア（神奈川県横浜市）
  • Year and Date: 2014-06-25
  • Invited
• [Presentation] Roles of common subunits within distinct multi-subunit complexes (2014)
  • Author(s): M. Horikoshi
  • Organizer: Keystone Symposia-Transcriptional Regulation
  • Place of Presentation: サンタフェ（米国）
  • Year and Date: 2014-02-04 – 2014-02-09
• [Presentation] Roles of generic subunits within distinct multi-subunit complexes (2013)
  • Author(s): M. Horikoshi
  • Organizer: 2013 Global Biomarker Conference
  • Place of Presentation: トロント（カナダ）
  • Year and Date: 2013-04-26
  • Invited
• [Presentation] An imaginative, creative, original, and competitive scientific journey with nature’s mysterious cell over 30 years (2013)
  • Author(s): M.Horikoshi
  • Organizer: Cold Spring Harbor Laboratory Meeting- From Base Pair to Body Plan: Celebrating 60 years of DNA
  • Place of Presentation: Cold Spring Harbor (NY), USA
• [Presentation] “DESS”, “MUFC” & “FALC” strategies based on “Modification web” & “Signal router” theories on histone modification system (2012)
  • Author(s): M.Horikoshi
  • Organizer: Cold Spring Harbor Laboratory Meeting- Epigenetics & Chromatin
  • Place of Presentation: Cold Spring Harbor (NY), USA
• [Presentation] “Modification web” & “Signal router” theories on histone modification system and their application to development of cancer drugs
  • Author(s): M.Horikoshi
  • Organizer: Keystone Symposia-Epigenetic Marks and Cancer Drugs
  • Place of Presentation: Santa Fe (NM), USA
  • Invited
• [Presentation] ヒストン化学修飾システムに関する”Modification web theory” 及び”Signal router theory”に基づいての”DESS”、 ”MUFC” 及び”FALC”戦略
  • Author(s): 堀越 正美
  • Organizer: 第３５回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場他、福岡市
  • Invited