Uncovering the molecular mechanism of c-Myc/Max transcriptional factor complex-mediated preservation of embryonic stem cell state

揭示c-Myc/Max转录因子复合物介导的胚胎干细胞状态保存的分子机制

• 批准号: 22590275
• 负责人: OKUDA Akihiko
• 金额: $ 2.91万
• 依托单位: Saitama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590275/
• 关键词: 発生医学; ES細胞; 未分化性; 自己増殖性; 多分化能; 転写因子; Myc; Max; Oct3/4; c-Myc; 自己増殖; Myc module活性; Core module活性; 細胞移植

Embryonic stem (ES) cells are defined by their two remarkable properties, i.e., pluripotent and indefinite self-renewal properties. Although some papers had suggested the involvement of Myc family proteins including c-Myc protein for sustaining these prominent properties which ES cells have, this issue has never been addressed from the gene targeting analyses. Therefore, we conducted homozygous knockout of Max gene encoding an indispensable partner protein for all three Myc proteins (c-Myc, N-Myc and L-Myc) to exert their transcriptional activities as well as oncogensis promoting activities.

胚胎茎（ES）细胞由它们的两个显着特性，即多能和无限期的自我更新特性定义。尽管一些论文提出了包括C-MYC蛋白在内的MYC家族蛋白的参与，以维持ES细胞所具有的这些突出特性，但此问题从未从靶向分析的基因中解决。因此，我们对所有三种MYC蛋白（C-MYC，N-MYC和L-MYC）编码的Max基因进行了纯合子敲除，以发挥其转录活性以及促进活性。

项目成果

Zappavigna V, Nicolis, SK. Emx2 is a dose-dependent negative regulator of Sox2 telencephalic enhancers

Zappavigna V，尼科利斯，SK。

• 发表时间: 2012
• 期刊: Nucleic Acids Res.
• 作者: Mariani J;Favaro R;Lancini C;Vaccari G;Ferri ALM;Bertolini J;Tonoli D;Latorre E;Caccia R;Ronchi A;Ottolenghi S;Miyagi S;Okuda A
• 通讯作者: Okuda A

Ground state condition renders Mye activity redundant in ES cells for their indefinite self-renewal

基态条件使得 ES 细胞中的 Mye 活性变得多余，以实现无限期的自我更新

• 发表时间: 2011
• 作者: Tsukide;T.;Kobayashi;A.;Miyasaka;T. Morita;T.;Mizoroki;T.;Saito;Y.;Ihara;Y. Takashima;A.;Noguchi;N. Fukamizu;A.;Hirotsu;Y.;Ohtsuji;M.;Katsuoka;F. and Yamamoto M;菱田友昭
• 通讯作者: 菱田友昭

Ground state condition renders Myc activity redundant in ES cells for their indefinite self-renewal

基态条件使得 ES 细胞中的 Myc 活性变得多余，以实现无限期的自我更新

• 发表时间: 2011
• 作者: Tomoaki Hishida;Akihiko Okuda
• 通讯作者: Akihiko Okuda

Integration of exogenous DNA into mouse embryonic stem cell chromosome shows preference into genes and frequent modification at junctions

外源 DNA 整合到小鼠胚胎干细胞染色体中显示出对基因的偏好以及连接处的频繁修饰

• 发表时间: 2010
• 期刊: Chromosome Research
• 影响因子: 2.6
• 作者: Pepe;A.E.;et al.;土谷佳樹;Keiichiro Suzuki
• 通讯作者: Keiichiro Suzuki

Max was identified as a repressor of germ-cell related gene expression in mouse embryonic stem cells.

Max 被鉴定为小鼠胚胎干细胞中生殖细胞相关基因表达的抑制因子。

• 发表时间: 2013
• 期刊: Nat. Commun.
• 作者: Maeda I;Okamura D;Tokitake Y;Ikeda M;Kawaguchi H;Mise N;Abe K;Noce T;Okuda A;Matsui Y.
• 通讯作者: Matsui Y.