Comprehensive analyses of signals of Wnt and nuclear receptors in adipogenesis through proteomics

• Project/Area Number: 20390090
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: SAKAI Juro The University of Tokyo, 先端科学技術研究センター, 教授 (80323020)
• Co-Investigator(Kenkyū-buntansha): TANAKA Toshiya 東京大学, 先端科学技術研究センター, 特任准教授 (20396930) ; KAWAMURA Takeshi 東京大学, 先端科学技術研究センター, 特任助教 (70306835)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000); Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2008: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: COUP-TFII / PPARγ / エピゲノム / βカテニン / Wnt / 脂肪細胞分化 / 標的遺伝子のゲノムワイド解析 / PPAR_Y / ssカテニン

Research Abstract

We revealed that PPARγ regulates several genes involved in histone lysine methyltransferase genes thereby regulates adipogenesis. We also revealed that the mechanism by which Wnt/β-catenin inhibits adipogenesis. Wnt/β-catenin stimulates COUP-TFII gene expressions, whose gene product inhibits PPARγ2 gene expression through the recruitment of HDAC to the transcription regulatory region of PPARγ2.

Research Products

• [Journal Article] Wnt signaling and its downstream target N-myc regulate basal progenitors in the developing neocortex (2010)
  • Author(s): Kuwahara A, Hirabayashi Y, Knoepfler PS, Taketo MM, Sakai J, Kodama T, Gotoh Y
  • Journal Title: Development 137 Pages: 1035-1044
  • Peer Reviewed
• [Journal Article] Role of histone methylation and demethylation in adipogenesis and obesity. (Review) (2010)
  • Author(s): Okamura M, Inagaki T, Tanaka T, Sakai J
  • Journal Title: Organogenesis 6(1) Pages: 24-32
  • Peer Reviewed
• [Journal Article] Sterol regulatory element-binding protein 2 and nuclear factor Y controls human farnesyl diphosphate synthase expression and affects cell proliferation in hepatoblastoma cells (2010)
  • Author(s): Ishimoto K, Tachibana K, Hanano I, Yamasaki D, Nakamura H, Kawai M, Urano Y, Tanaka T, Hamakubo T, Sakai J, Kodama T, Doi T
  • Journal Title: Biochem J.Epub ahead of print.
  • Peer Reviewed
• [Journal Article] Role of histone methylation and demethylation in adipogenesis and obesity.(Review) (2010)
  • Author(s): Okamura M, et al
  • Journal Title: Organogenesis 6 Pages: 24-32
  • Peer Reviewed
• [Journal Article] Wnt signaling and its downstream target N-myc regulate basal progenitors in the developing neocortex. (2010)
  • Author(s): Kuwahara A, et al
  • Journal Title: Development 137 Pages: 1035-1044
  • Peer Reviewed
• [Journal Article] Obesity and Metabolic Syndrome in Histone Demethylase JHDM2a Deficient Mice (2009)
  • Author(s): Inagaki T, Tachibana M, Magoori K, Kudo H, Tanaka T, Okamura M, Naito M, Kodama T, Shinkai Y, Sakai J
  • Journal Title: Genes to Cells 14 Pages: 991-1001
  • Peer Reviewed
• [Journal Article] PPARγ/RXRα Heterodimer Targets Genes of Histone Modification Enzymes Setd8 and Regulates Adipogenesis through a Feed-back Mechanism (2009)
  • Author(s): Wakabayashi K, Okamura M, Tsutsumi S, Tanaka T, Hamakubo T, Kodama T, Aburatani H, Sakai J
  • Journal Title: Mol Cell Biol 29 Pages: 3544-3555
  • Peer Reviewed
• [Journal Article] COUP-TFII acts downstream of Wnt/β-catenin signal to silence PPARγ gene expression and repress adipogenesis (2009)
  • Author(s): Okamura M, Kudo H, Wakabayashi KI, Tanaka T, Nonaka A, Uchida A, Tsutsumi S, Sakakibara I, Naito M, Osborne TF, Hamakubo T, Ito S, Aburatani H, Yanagisawa M, Kodama T, Sakai J
  • Journal Title: Proc Natl Acad Sci U S A. 10 Pages: 5819-5824
  • Peer Reviewed
• [Journal Article] A small molecule that blocks fat synthesis by inhibiting the activation of SREBP. (2009)
  • Author(s): Kamisuki S, Mao Q, Abu-Elheiga L, Gu Z, Kugimiya A, Kwon Y, Shinohara T, Kawazoe Y, Sato S-i, Asakura K, Choo H-YP, Sakai J, Wakil SJ, Uesugi M
  • Journal Title: Chemistry & Biology 16 Pages: 882-892
  • Peer Reviewed
• [Journal Article] Sterol-Mediated Regulation of Human Lipin 1 Gene Expression in Hepatoblastoma Cells (2009)
  • Author(s): Ishimoto K, Nakamura H, Tachibana K, Yamasaki D, Ota A, Hirano K-i, Tanaka T, Hamakubo T, Sakai J, Kodama T, Doi T
  • Journal Title: J Biol Chem 284 Pages: 22195-22205
  • Peer Reviewed
• [Journal Article] Fasting-induced hypothermia and reduced energy production in mice lacking acetyl-CoA synthetase 2. (2009)
  • Author(s): Sakakibara I, Fujino T, Ishii M, Tanaka T, Shimosawa T, Miura S, Zhang W, Tokutake Y, Yamamoto J, Awano M, Iwasaki S, Motoike T, Okamura M, Inagaki T, Kita K, Ezaki O, Naito M, Kuwaki T, Chohnan S, Yamamoto TT, Hammer RE, Kodama T, Yanagisawa M, Sakai J
  • Journal Title: Cell Metabolism 9 Pages: 191-202
  • Peer Reviewed
• [Journal Article] PPARγ/RXRa Heterodimer Targets Genes of Histone Modification Enzymes Setd8 and Regulates Adipogenesis through a Feed-back Mechanism. (2009)
  • Author(s): Wakabayashi K, et al
  • Journal Title: Mol.Cell.Biol. 29 Pages: 3544-3555
  • Peer Reviewed
• [Journal Article] Obesity and Metabolic Syndrome in Histone Demethylase JHDM2a Deficient Mice. (2009)
  • Author(s): Inagaki T, et al
  • Journal Title: Genes to Cells 14 Pages: 991-1001
  • Peer Reviewed
• [Journal Article] PPARγ/RXRα Heterodimer Targets Genes of Histone Modification Enzymes Setd8 and Regulates Adipogenesis through a Feed-back Mechanism (2009)
  • Author(s): Wakabayashi K, et al
  • Journal Title: Mol.Cell.Biol. 29 Pages: 3544-3555
  • Peer Reviewed
• [Journal Article] COUP-TFII acts downstream of Wnt/β-catenin signal to silence PPARγ gene expression and repress adipogenesis (2009)
  • Author(s): Okamura M, et al
  • Journal Title: Proc Natl Acad Sci USA 106 Pages: 5819-5824
  • Peer Reviewed
• [Journal Article] Obesity and Metabolic Syndrome in Histone Demethylase JHDM2a Deficient Mice (2009)
  • Author(s): Inagaki T, et al
  • Journal Title: Genes to Cells 14 Pages: 991-1001
  • Peer Reviewed
• [Presentation] PPARγ/RXRα Heterodimer Targets Gene of Histone Modification Enzyme PR-Set7/Setd8 and Regulates Adipogenesis through a Positive Feedback Loop (2009)
  • Author(s): Sakai J, Aburatani H, Kodama T, Wakabayashi K, Tanaka T, Okamura M, Tsutsumi S, Hamakubo T
  • Organizer: 第32回日本分子生物学会, 第82回日本生化学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] 次世代シーケンサーを用いた脂肪細胞におけるエピゲノム研究 (2009)
  • Author(s): 酒井寿郎
  • Organizer: 第11回日本骨粗鬆症学会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-10-15
• [Presentation] 次世代シーケンサーを用いた脂肪細胞におけるエピゲノム研究(シンポジウム) (2009)
  • Author(s): 酒井寿郎
  • Organizer: 第110回日本骨粗鬆症学会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2009-10-15
• [Presentation] ヒストンリジンメチル化の脂肪細胞分化および肥満形成における役割 (2009)
  • Author(s): 酒井寿郎
  • Organizer: 第30回日本肥満学会
  • Place of Presentation: 浜松
  • Year and Date: 2009-10-09
• [Presentation] ヒストンリジンメチル化の脂肪細胞分化および肥満形成における役割(シンポジウム) (2009)
  • Author(s): 酒井寿郎
  • Organizer: 第30回日本肥満学会
  • Place of Presentation: アクトシティ浜松(静岡県)
  • Year and Date: 2009-10-09
• [Presentation] The peroxisome proliferator-activated receptor gamma/retinoid X receptor alpha heterodimer targets the histone modification enzyme PR-Set7/Setd8 gene and regulates adipogenesis through a positive feedback loop (2009)
  • Author(s): Tanaka T, Wakabayashi K, Okamura M, Tsutsumi S, Hamakubo T, Kodama T, Aburatani H, Sakai J
  • Organizer: EMBO Conference on Nuclear Receptors
  • Place of Presentation: Croatia
  • Year and Date: 2009-09-28
• [Presentation] The peroxisome proliferator-activated receptor gamma/retinoid X receptor alpha heterodimer targets the histone modification enzyme PR-Set7/Setd8 gene and regulates adipogenesis through a positive feedback loop. (2009)
  • Author(s): Tanaka T, et al
  • Organizer: EMBO Conference on Nuclear Receptors
  • Place of Presentation: Croatia, Dubrovnik
  • Year and Date: 2009-09-28
• [Presentation] COUP-TFII acts downstream of Wnt/β-catenin signal to silence PPARγ gene expression and repress adipogenesis (2008)
  • Author(s): 酒井寿郎
  • Organizer: 第31回日本分子生物学会, 第81回日本生化学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] COUP-TFII acts downstream of Wnt/β-catenin signal to silence PPARγ gene expression and repress adipogenesis (2008)
  • Author(s): 酒井寿郎
  • Organizer: 第31回日本分子生物学会、第81回日本生化学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Remarks] 酒井寿郎:特集記事「脂肪細胞の分化や肥満に関与するエピゲノムのしくみを解明!」, Nature Japan, 2009年11月13日付
• [Remarks] 酒井寿郎 他:「遺伝子の働き制御するエピゲノム」, 朝日新聞, 2009年9月29日付
• [Remarks]
  • URL: http://www.lsbm.org/staff/sakai.html