GCNF mediated DNA methylation and stem cell differentiation

GCNF介导的DNA甲基化和干细胞分化

• 批准号: 19570146
• 负责人: SATO Noriko
• 金额: $ 2.91万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19570146/
• 关键词: DNAメチル化; エピジェネティック制御; GCNF; Oct-3; 4; Dnmt3; DNA メチル化

GCNF (germ cell nuclear factor) is expressed at the gastrulation stage during embryonic development. GCNF represses pluripotency genes such as Oct-3/4 and Nanog and induces DNA methylation of their regulatory regions. In this project, the specific monoclonal antibodies against GCNF have been newly prepared in order to analyze the endogenous GCNF protein during murine ES cell differentiation. By the co-immunoprecipitation study, interaction between endogenous GCNF and Dnmt3 proteins was confirmed. At the beginning of ES differentiation, the expression level of GCNF was low, but it interacts with Dnmt3a2 and Dnmt3b. At the later stage, GCNF was transiently upregulated and it interacts with Dnmt3a1. Mass spectrometry analysis has revealed that anti-GCNF immunoprecipitates contain Trim28 and PELP1 complex, but the further analyses will be required to assess its functional significance.

生殖细胞核因子（GCNF）在胚胎发育的原肠形成阶段表达。GCNF抑制Oct-3/4和Nanog等多能基因，诱导其调控区域的DNA甲基化。本项目新制备GCNF特异性单克隆抗体，分析小鼠ES细胞分化过程中内源性GCNF蛋白的表达。通过共免疫沉淀研究，证实了内源性GCNF与Dnmt3蛋白之间的相互作用。在ES分化初期，GCNF表达水平较低，但与Dnmt3a2和Dnmt3b相互作用。在后期，GCNF短暂上调，并与Dnmt3a1相互作用。质谱分析显示，抗gcnf免疫沉淀含有Trim28和PELP1复合物，但需要进一步分析以评估其功能意义。

项目成果

核内受容体によるDNAメチル化誘導機構

核受体诱导DNA甲基化机制

• 发表时间: 2007
• 作者: 佐藤憲子;新井賢一
• 通讯作者: 新井賢一

核内受容体GCNFによるDNAメチル化誘導機構

核受体GCNF诱导DNA甲基化机制

• 发表时间: 2007
• 作者: 恩田真紀;竹原清日;高橋延行;廣瀬正明;佐藤憲子
• 通讯作者: 佐藤憲子