Alterations in epigenetic modifications during oocyte growth in mice
Alterations in epigenetic modifications during oocyte growth in mice
复制标题
DOI：
10.1530/rep-06-0025
复制
发表时间：
2007-01-01
期刊：
影响因子：
3.8
通讯作者：
Aoki, Fugaku
中科院分区：
文献类型：
--
作者：
Kageyama, Shun-ichiro;Liu, Honglin;Aoki, Fugaku
在卵母细胞生长过程中，染色质结构发生整体改变，基因表达沉默。为了研究表观遗传修饰在这些现象的调节中的作用，我们检查了小鼠卵母细胞生长过程中整体 DNA 甲基化和各种组蛋白修饰的变化，即 H3K9、HUM、HU5 和 H4K12 的乙酰化以及 H3K4 和 H3K9 的甲基化。免疫细胞化学分析表明，所有这些修饰的信号强度在生长过程中都会增加，并且完全生长的生发囊泡 (GV) 阶段卵母细胞显示出最多的修饰。由于历史上大多数赖氨酸残基的乙酰化和 H3K4 的甲基化与活跃的基因表达相关，因此这些修饰水平的增加似乎与 GV 期卵母细胞中的基因沉默无关。鉴于存在两种类型的GV期卵母细胞，它们具有不同的染色质构型和转录活性，因此比较了这两种类型的表观遗传修饰状态。 SN（包围核仁）型卵母细胞中所有表观遗传修饰的水平均高于NSN（不包围核仁）型卵母细胞，其中高度浓缩的染色质集中在核仁周围区域，基因表达沉默。此外，RT-PCR 显示催化组蛋白修饰的各种酶的表达水平随着卵母细胞的生长而增加。总而言之，结果表明所有表观遗传修饰在卵母细胞生长过程中以一致的方式增加，并表明这些增加与基因表达无关。
During oocyte growth, chromatin structure is altered globally and gene expression is silenced. To investigate the involvement of epigenetic modifications in the regulation of these phenomena, changes in global DNA methylation and in various histone modifications, i.e. acetylation of H3K9, HUM, HU5, and H4K12, and methylation of H3K4 and H3K9, were examined during the growth of mouse oocytes. Immunocytochernical analysis revealed that the signal intensities of all these modifications increased during growth and that fully grown, germinal vesicle (GV)-stage oocytes showed the most modifications. Since acetylation of most of the lysine residues on histories and methylation of H3K4 are associated with active gene expression, the increased levels of these modifications do not seem to be associated with gene silencing in GV-stage oocytes. Given that there are two types of GV-stage oocytes with different chromatin configurations and transcriptional activities, the epigenetic modification statuses of these two types were compared. The levels of all the epigenetic modifications examined were higher in the SN(surrounded nucleolus)-type oocytes, in which highly condensed chromatin is concentrated in the area around the nucleolus and gene expression is silenced than in the NSN(not surrounded nucleolus)-type oocytes, in which less-condensed chromatin does not surround the nucleolus and gene expression is active. In addition, the expression levels of various enzymes that catalyze histone modifications were shown by RT-PCR to increase with oocyte growth. Taken together, the results show that all of the epigenetic modifications increased in a concerted manner during oocyte growth, and suggest that these increases are not associated with gene expression.