Analysis of adipocyte accumulation mechanism through histone H4 methylation

• Project/Area Number: 26860227
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human genetics
• Research Institution: Sasaki Foundation (2015-2017); Juntendo University (2014)
• Principal Investigator: Fujii Tomoaki 公益財団法人佐々木研究所, 附属研究所, 部長(移行) (10511420)
• 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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: メチルトランスフェラーゼ / エピジェネティクス / 脂肪細胞分化

Outline of Final Research Achievements

The aim of this study is to unclear the function of Smyd2 and Smyd3, both of which methylate the histone H4, in adipocyte accumulation. To compare the differentiation into adipocyte in mesenchymal stem cell and preadipocytes of Smyd2-/- and wild type mice, the expression of their adipogenic marker genes was examined. There were no significant differences in their expression between Smyd2-/- and wild type mice. The body weight of Smyd2-/-;Smyd3-/-mice elevated compared with wild type with a high-fat diet or normal chow. Smyd2-/-;Smyd3-/- mice also had higher plasma total cholesterol and free fatty acids levels than wild type mice. In further study, we will perform these experiments with other genotype mice.

Research Products

• [Journal Article] Identification and characterization of a novel <i>adenomatous polyposis coli</i> mutation in adult pancreatoblastoma (2018)
  • Author(s): Yamaguchi S, Fujii T, Izumi Y, Fukumura Y, Han M, Yamaguchi H, Akita T, Yamashita C, Kato S, Sekiya T.
  • Journal Title: Oncotarget Volume: 9(12) Issue: 12 Pages: 10818-10827
  • DOI: 10.18632/oncotarget.24017
  • Peer Reviewed / Open Access
• [Journal Article] Establishment and analysis of a novel mouse line carrying a conditional knockin allele of a cancer-specific FBXW7 mutation. (2018)
  • Author(s): Ikenoue T, Terakado Y, Zhu C, Liu X, Ohsugi T, Matsubara D, Fujii T, Kakuta S,Kubo S, Shibata T, Yamaguchi K, Iwakura Y, Furukawa Y.
  • Journal Title: Sci Rep Volume: 8 Issue: 1 Pages: 2021-2021
  • DOI: 10.1038/s41598-018-19769-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Smyd5 plays pivotal roles in both primitive and definitive hematopoiesis during zebrafish embryogenesis. (2016)
  • Author(s): Fujii T, Tsunesumi S, Sagara H, Munakata M, Hisaki Y, Sekiya T, Furukawa Y,Sakamoto K, Watanabe S.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 29517-29517
  • DOI: 10.1038/srep29157
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A novel mouse model of intrahepatic cholangiocarcinoma induced by liver-specific Kras activation and Pten deletion. (2016)
  • Author(s): Ikenoue T, Terakado Y, Nakagawa H, Hikiba Y, Fujii T, Matsubara D, Noguchi R, Zhu C, Yamamoto K, Kudo Y, Asaoka Y, Yamaguchi K, Ijichi H, Tateishi K, Fukushima N, Maeda S, Koike K, Furukawa Y
  • Journal Title: Sci Rep Volume: 印刷中 Issue: 1 Pages: 23899-23899
  • DOI: 10.1038/srep23899
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An impact of Chromosome 17q deletion in the primary lesion of colorectal cancer on liver metastasis. (2016)
  • Author(s): Kawai M, Komiyama H, Hosoya M, Okubo H, Fujii T, Yokoyama N, Sato C, Ueyama T, Okuzawa A, Goto M, Kojima Y, Takahashi M, Sugimoto K, Ishiyama S, Munakata S, Ogura D, Niwa S, Tomiki Y, Ochiai T, Sakamoto K:
  • Journal Title: Oncology Letters Volume: 12(6) Issue: 6 Pages: 4773-4778
  • DOI: 10.3892/ol.2016.5271
  • Peer Reviewed / Open Access
• [Journal Article] Critical roles of DNase1l3l in lens nuclear degeneration in zebrafish. (2014)
  • Author(s): Iida A, Tabata Y, Baba Y, Fujii T, Watanabe S
  • Journal Title: Biochimie Volume: 106 Pages: 68-74
  • Peer Reviewed
• [Presentation] 成人膵芽腫に見られた新規Adenoma polyposis coli (APC)遺伝子変異の機能解析 (2017)
  • Author(s): 泉 祐毅 山口 茂夫 藤井 智明 韓 敏 野崎 由美 山下 親正 加藤 俊介
  • Organizer: 第 15 回日本臨床腫瘍学会学術集会
• [Presentation] Expression and functional analysis of Smyd5 in zebrafish. (2016)
  • Author(s): Tomoaki Fujii, Shin-ichiro Tsunesumi, Hiroshi Sagara, Miyo Munakata, Yoshihiro Hisaki, Takao Sekiya,Yoichi Furukawa, Kazuhiro Sakamoto, and Sumiko Watanabe.
  • Organizer: American Society for Cell Biology Annual Meeting
  • Place of Presentation: Moscone Center San Francisco, California
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] 癌で高頻度に見られるFBXW7変異の条件的ノックインマウスの樹立 (2016)
  • Author(s): 池上 恒雄、寺門 侑美、藤井 智明、松原 大祐、山口 貴世志、 古川 洋一
  • Organizer: 第76回日本癌学会学術総会
  • Place of Presentation: パシフィッコ横浜
  • Year and Date: 2016-10-06
• [Presentation] Expression and functional analysis of Smyd5 in zebrafish (2014)
  • Author(s): Tomoaki Fujii, Shin-ichiro Tsunesumi, Shingo Ito, Yoichi Furukawa, Kazuhiro Sakamoto, Sumiko Watanabe
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィッコ横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] The subsequent epithelial-mesenchymal and mesenchymal-epithelial transition model barely depicts colon cancer metastasis (2014)
  • Author(s): Yu Okazawa, Kosuke Mizukoshi, Hiromitsu Komiyama, Tomoaki Fujii, Michitoshi Goto, Sonoko Habu, Kazuhiro Sakamoto, Akira Orimo
  • Organizer: 第73回日本癌学会学術集会
  • Place of Presentation: パシフィッコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Expression and functional analysis of Smyd5 in zebrafish (2014)
  • Author(s): Tomoaki Fujii, Shin-ichiro Tsunesumi, Shingo Ito, Yoichi Furukawa, Kazuhiro Sakamoto, Sumiko Watanabe.
  • Organizer: 第２０回小型魚類研究会
  • Place of Presentation: 慶應義塾大学薬学部（芝 共立キャンパス）
  • Year and Date: 2014-09-20 – 2014-09-21
• [Presentation] ヒストンH4K5メチル化修飾についての機能解析 (2014)
  • Author(s): 藤井智明，西田知恵美， Heissig Beate ,古川洋一,坂本一博，服部浩一
  • Organizer: 第28回モロシヌス研究会
  • Place of Presentation: 国立遺伝学研究所・修善寺総合会館
  • Year and Date: 2014-06-27 – 2014-06-28