Modulation of osteoblastic differentiation by G9a and ESET

• Project/Area Number: 26861562
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional basic dentistry
• Research Institution: Tsurumi University
• Principal Investigator: Ideno Hisashi 鶴見大学, 歯学部, 学部助手 (40435699)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: エピジェネティクス / ヒストンメチル化 / 骨芽細胞 / 骨芽細胞分化 / 転写制御 / 転写活性化

Outline of Final Research Achievements

The purpose of this study was to elucidate role of G9a and ESET, both histone methyltransferases, during osteoblastic differentiation. Especially we focused on how they regulate the function of Runx2, which is a critical transcription factor for osteoblastic differentiation. We found that G9a and ESET enhanced transcriptional activity of Runx2. In G9a-knockout osteoblasts, we observed decreased expression of osteocalcin mRNA,　while expression of Runx2 was not affected. Moreover, we found that the C-terminal region of G9a was necessary for binding with Runx2 and enhancement its transcription activation. These results suggest that G9a is required for proper function of Runx2 during osteoblastic differentiation.

Research Products

• [Journal Article] Bardet-Biedl syndrome 3 regulates the development of cranial base midline structures (2017)
  • Author(s): Kawasaki M, Izu Y, Hayata T, Ideno H, Nifuji A, Sheffield VC, Ezura Y, Noda M.
  • Journal Title: Journal of Biomaterials Science, Polymer Edition. Volume: 89 Pages: 179-190
  • DOI: 10.1016/j.bone.2016.02.017
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Essential roles of G9a in cell proliferation and differentiation during tooth development. Experimental Cell Research. (2017)
  • Author(s): Kamiunten T, Ideno H, Shimada A, Arai Y, Terashima T, Tomooka Y, Nakamura Y, Nakashima K, Kimura H, Shinkai Y, Tachibana M, Nifuji A
  • Journal Title: Experimental Cell Research Volume: 印刷中
  • DOI: 10.1016/j.yexcr.2017.05.013
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] BMP-2 Enhances Lgr4 Gene Expression in Osteoblastic Cells. (2016)
  • Author(s): Komatsu K, Shibata T, Shimada A, Ideno H, Nakashima K, Tabata Y, Nifuji A.
  • Journal Title: Journal of Biomaterials Science, Polymer Edition. Volume: 27 Pages: 419-430
  • DOI: 10.1080/09205063.2016.1139486
  • Peer Reviewed / Open Access
• [Journal Article] Coordinated expression of H3K9 histone methyltransferases during tooth development in mice. (2015)
  • Author(s): Kamiunten T, Ideno H, Shimada A, Nakamura Y, Kimura H, Nakashima K, Nifuji A.
  • Journal Title: Histochemistry and Cell Biology. Volume: 143 Pages: 259-266
  • DOI: 10.1007/s00418-014-1284-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] H3K9MTase G9a is essential for the differentiation and growth of tenocytes in vitro. (2015)
  • Author(s): Wada S, Ideno H, Shimada A, Kamiunten T, Nakamura Y, Nakashima K, Kimura H, Shinkai Y, Tachibana M, Nifuji A.
  • Journal Title: Histochem. Cell Biol. Volume: in press Pages: 13-20
  • DOI: 10.1007/s00418-015-1318-2
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Roles of the histone methyltransferase G9a in the development and differentiation of mesenchymal tissues (2015)
  • Author(s): Hisashi Ideno, Kazuhisa Nakashima, Akira Nifuji
  • Journal Title: JPFSM Volume: 4(5) Issue: 5 Pages: 357-362
  • DOI: 10.7600/jpfsm.4.357
  • NAID: 130005113195
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ヒストンメチル化酵素G9aはマウス歯胚の増殖と分化を制御する (2017)
  • Author(s): 出野 尚、上運天太一、島田明美、寺島達夫、中島和久、友岡康弘、中村芳樹、木村 宏、立花 誠、二藤 彰
  • Organizer: 第35回日本骨代謝学会学術集会
• [Presentation] H3K9MTase G9a regulates tooth development in mice (2017)
  • Author(s): Ideno H., Kamiunten T., Shimada A., Terashima T., Nakashima K., Tomooka Y., Nakamura Y., Kimura H., Tachibana M., Nifuji A
  • Organizer: 第39回米国骨代謝学会（ASBMR）
  • Int'l Joint Research
• [Presentation] Histone methyltransferase G9a is essential for osteoblastic differentiation and skull bone formation during development (2017)
  • Author(s): Ideno H., Komatsu K., Shimada A., Arai Y., Nakashima K., Tachibana M., Kimura H., Nifuji A）
  • Organizer: 第57回米国細胞生物学会議（ASCB）
  • Int'l Joint Research
• [Presentation] ヒストンメチル化酵素 G9aの骨芽細胞分化における機能 (2016)
  • Author(s): 出野尚、小松浩一郎、島田明美、新井嘉則、中島和久、荒木良子、安倍真澄、立花誠、木村宏、二藤彰
  • Organizer: 第39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: 2016-11-30
• [Presentation] Essential roles of H3K9MTase G9a during tooth development (2016)
  • Author(s): 出野尚、上運天太一、島田明美、中村芳樹、中島和久、木村宏、立花誠、二藤彰
  • Organizer: 第34回日本骨代謝学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2016-07-21
• [Presentation] Histone methyltransferase G9a is essential for osteoblastic differentiation and proliferation in vitro, and skull bone formation in vivo (2015)
  • Author(s): Hisashi Ideno, Koichiro Komatsu, Akemi Shimada, Taichi Kamiunten, Yoshinori Arai, Kazuhisa Nakashima, Ryoko Araki, Yoshiki Nakamura, Masumi Abe, Makoto Tachibana, Hiroshi Kimura, Akira Nifuji
  • Organizer: 2015 The American Society for Cell Biology Annual Meeting
  • Place of Presentation: San Diego Convention Center, San Diego, CA, USA
  • Year and Date: 2015-12-12
  • Int'l Joint Research
• [Presentation] Deletion of G9a, histone methyltransferase, causes impaired bone formation (2015)
  • Author(s): Hisashi Ideno, Koichiro Komatsu, Akemi Shimada, Taichi Kamiunten, Yoshinori Arai, Kazuhisa Nakashima, Ryoko Araki, Yoshiki Nakamura, Masumi Abe, Makoto Tachibana, Hiroshi Kimura, Akira Nifuji
  • Organizer: 2015 Australia and New Zealand Bone & Mineral Society
  • Place of Presentation: Hotel Grand Chancellor Hobart, Hobart, TAS, Australia
  • Year and Date: 2015-11-01
  • Int'l Joint Research
• [Presentation] ヒストンメチル化酵素G9a欠損マウスは骨形成阻害を示す (2015)
  • Author(s): 出野 尚, 小松浩一郎, 島田明美, 上運天太一, 新井嘉則, 中島和久, 荒木良子, 中村芳樹, 安倍真澄, 立花 誠, 木村 宏, 二藤 彰
  • Organizer: 第33回日本骨代謝学会学術集会
  • Place of Presentation: 京王プラザホテル （東京都新宿区）
  • Year and Date: 2015-07-23
• [Presentation] ヒストンメチル化酵素G9aによる間葉系細胞の増殖と分化の調節 (2014)
  • Author(s): 出野 尚、島田明美、上運天太一、和田悟史、小松浩一郎、立花 誠、荒木良子、中村芳樹、安倍真澄、中島和久、二藤 彰
  • Organizer: 第56回歯科基礎医学会学術大会
  • Place of Presentation: 福岡国際会議場・福岡県・福岡市
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] The functions of histone methyltransferase G9a during growth and differentiation of mesenchymal cells (2014)
  • Author(s): 出野 尚、島田明美、上運天太一、和田悟史、小松浩一郎、荒木良子、中村芳樹、安倍真澄、中島和久、二藤 彰
  • Organizer: 第32回日本骨代謝学会学術集会
  • Place of Presentation: 大阪国際会議場・大阪府・大阪市
  • Year and Date: 2014-07-24 – 2014-07-26