Functional analysis of a methyl-CpG binding protein CIBZ in the regulation of cardiogenesis

• Project/Area Number: 25460368
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Matsuda Eishou 奈良先端科学技術大学院大学, バイオサイエンス研究科, 助教 (00335481)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ES細胞 / 細胞分化 / 心筋細胞 / CIBZ（ZBTB38） / Brachyury（T） / Mesp1 / 転写抑制 / 中胚葉 / BTBジンクフィンガー型転写因子 / Brachyury (T) / 胚様体 / ES細胞の分化 / メチル化DNA結合タンパク質 / CIBZ / Znフィンガー / ノックアウトマウス / Creマウス / 転写因子 / 転写制御 / 胚性幹（ES）細胞 / 心筋の発生分化 / BTB型のジンクフィンガータンパク質 / DNAメチル化

Outline of Final Research Achievements

The transcription factors T and Mesp1 play key roles in guiding embryonic stem cells (ESCs) toward mesodermal and cardiac lineages, respectively. Although a growing body of evidence indicates that T and Mesp1 regulate downstream target genes, the molecular mechanisms behind maintenance of their silencing state in the undifferentiated ESCs remain poorly understood.
Here we show that CIBZ, a BTB domain zinc finger transcriptional factor, is a novel negative regulator of mesodermal and cardiac differentiation of ESCs. We also show the direct inhibitory binding of CIBZ to T and Mesp1 promoters. These data provide new insights into the role of CIBZ in the regulation of cardiac specification of ESCs and show that CIBZ is critical for maintaining the silenced state of T and Mesp1 in ESCs.

Research Products

• [Journal Article] CIBZ Regulates Mesodermal and Cardiac Differentiation of by Suppressing T and Mesp1 Expression in Mouse Embryonic Stem Cells (2016)
  • Author(s): Kotoku T, Kosaka K, Nishio M, Ishida Y, Kawaichi M, Matsuda E
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 34188-34188
  • DOI: 10.1038/srep34188
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Functional analysis of a BTB domain-containing zinc finger protein CIBZ in mammalian cells (2016)
  • Author(s): Eishou Matsuda, Yu Oikawa, Tomonori Nishii, Tomomi Kotoku and Masashi Kawaichi
  • Organizer: International Conference on Molecular Biology and Biotechnology
  • Place of Presentation: クアラルンプール、マレーシア
  • Year and Date: 2016-03-09
  • Int'l Joint Research / Invited
• [Presentation] マウス ES 細胞の心筋分化における BTB ジンクフィンガータンパク質 CIBZ の機能解析 (2015)
  • Author(s): 西尾 美紀, 幸得 友美, 松田 永照, 石田 靖雅, 川市 正史
  • Organizer: 第38回日本分子生物学会年会
  • 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