The mechanisms of chromatin remodeling in mammalian oocyte maturation and meiosis

哺乳动物卵母细胞成熟和减数分裂中染色质重塑的机制

• 批准号: 18390452
• 负责人: TANAKA Mamoru
• 金额: $ 8.2万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390452/
• 关键词: Linker histone; Oocyte; Epigenetics; Hlfoo; ノックアウト

Meiotic maturation is controlled through activation of the major cell cycle kinase, MPF (maturation promoting factor). Although linker histone Hi is a good substrate for cyclin dependent kinases, the definitive function of phosphorylated linker histone is poorly understood. In the mouse oocyte, an oocyte-specific linker histone, H1foo, is only expressed instead of somatic type one. We have shown that H1foo plays an important role in murine early development, and influences the stability of chromatin structure. Here, we show that H1foo is phosphorylated by MPF in vitro and in vivo. We next demonstrated that phosphorylated H1foo increases its mobility by using the technique of FRAP (fluorescence recovery after photobleaching). To assess the function of H1foo in the course of oocyte maturation, we generated targeted deletion in exon 2 of H1foo in BM mice. Male H1foo null mice showed no phenotype. However, oocytes from these animals do not develop normally; they undergo parthenogenetic cell division in the ovary, exhibit abnormal polar bodies, are detached from the cumulus granulosa cell layer, and display spindle and nuclear anomalies. This result suggests that H1foo is essential for maturation of GV-stage oocytes.

减数分裂成熟是通过激活主要的细胞周期激酶MPF（成熟促进因子）来控制的。虽然连接体组蛋白Hi是细胞周期蛋白依赖性激酶的良好底物，但磷酸化连接体组蛋白的决定性功能知之甚少。在小鼠卵母细胞中，仅表达卵母细胞特异性连接体组蛋白H1 foo，而不是体细胞类型1。H1 foo在小鼠早期发育中起重要作用，并影响染色质结构的稳定性。在这里，我们表明，H1 foo是由MPF在体外和体内磷酸化。我们接下来通过使用FRAP（光漂白后的荧光恢复）技术证明磷酸化的H1 foo增加了其迁移率。为了评估H1 foo在卵母细胞成熟过程中的功能，我们在BM小鼠中产生H1 foo外显子2的靶向缺失。雄性H1 foo基因敲除小鼠未显示表型。然而，这些动物的卵母细胞不能正常发育;它们在卵巢中进行孤雌生殖细胞分裂，表现出异常的极体，与卵丘颗粒细胞层分离，并显示纺锤体和核异常。这一结果表明，H1 foo是必要的成熟的GV期卵母细胞。

项目成果

生殖細胞におけるエピジェネティック制御

生殖细胞的表观遗传调控

• 发表时间: 2007
• 作者: Tanaka;M;田中 守
• 通讯作者: 田中 守

Differential Zonal Expression and Adrenocorticotropin Regulation of SPARC, a Matricellular Protein, in the Midgestation Human Fetal Adrenal Gland: Implications for Adrenal Development

SPARC（一种基质细胞蛋白）在妊娠中期人胎儿肾上腺中的差异区带表达和促肾上腺皮质激素调节：对肾上腺发育的影响

• 发表时间: 2006
• 期刊: J Clin Endocrinol Metab 91
• 作者: Ishimoto;H;et. al.
• 通讯作者: et. al.

Midkine, a Heparin-Binding Growth Factor, Selectively Stimulates Proliferation of Definitive Zone Cells of the Human Fetal Adrenal Gland

Midkine 是一种肝素结合生长因子，选择性刺激人胎儿肾上腺限定区细胞的增殖

• 发表时间: 2006
• 期刊: J Clin Endocrinol Metab 91
• 作者: Ishimoto;H;et. al.
• 通讯作者: et. al.

「研究成果報告書概要(和文)」より

摘自《研究结果报告摘要（日文）》

• 发表时间: 2005
• 作者: Kawauchi;et. al.;Nishimura et al.;Dezawa et al.;Yoshizawa et al.;星野 幹雄;星野 幹雄
• 通讯作者: 星野 幹雄

Chromatin modification in the course of oocyte maturation and fertilization

卵母细胞成熟和受精过程中的染色质修饰

• 发表时间: 2007
• 作者: Tanaka;M
• 通讯作者: M