Epigenetic modification affecting expression of cell polarity and cell fate genes to regulate lineage specification in the early mouse embryo.
Epigenetic modification affecting expression of cell polarity and cell fate genes to regulate lineage specification in the early mouse embryo.
复制标题
DOI：
10.1091/mbc.e10-01-0053
复制
发表时间：
2010-08-01
影响因子：
3.3
通讯作者：
Zernicka-Goetz M
中科院分区：
文献类型：
--
作者：
Parfitt DE;Zernicka-Goetz M
在这项研究中，细胞行为和卵裂球极性的背景下，Carm1过表达的植入前小鼠胚胎。结果表明，Carm1水平可以影响关键细胞极性的表达和与细胞行为和谱系分配变化相关的命运决定。小鼠胚胎的内细胞和外细胞的形成将多能性内细胞团（ICM）与分化中的滋养外胚层（TE）区分开来。Carm1使组蛋白H3R17和R26甲基化，将细胞导向ICM而不是TE。为了理解这种表观遗传修饰指导细胞命运的机制，我们用不同Carm1水平的体内标记细胞生成了胚胎，使用延时成像来揭示它们行为的动态，并将其与细胞极化相关。这表明，Carm1通过促进不对称分裂影响细胞命运，这种不对称分裂直接导致一个子细胞进入细胞内部，并且细胞吞噬，其中具有较低Carm1水平的相邻细胞竞争外部位置。这与细胞极性蛋白的表达模式和空间分布的变化有关：具有较高Carm1水平的细胞显示Par3的表达和顶端定位减少，并且顶端蛋白aPKC的拮抗剂PKC II的表达显著增加。小鼠Par1同源物EMK1的表达和基底外侧定位伴随增加。增加Carm1也减少Cdx2表达，这是TE分化的关键转录因子。这些结果证明了特定表观遗传修饰的程度如何影响细胞极性和决定命运的基因的表达，以确保小鼠胚胎中的谱系分配。
In this study, cell behavior and blastomere polarity are examined in the context of Carm1 overexpression in the preimplantation mouse embryo. The results suggest that Carm1 levels can affect the expression of key cell polarity and fate-determining in association with changes in cell behavior and lineage allocation. Formation of inner and outer cells of the mouse embryo distinguishes pluripotent inner cell mass (ICM) from differentiating trophectoderm (TE). Carm1, which methylates histone H3R17 and R26, directs cells to ICM rather that TE. To understand the mechanism by which this epigenetic modification directs cell fate, we generated embryos with in vivo–labeled cells of different Carm1 levels, using time-lapse imaging to reveal dynamics of their behavior, and related this to cell polarization. This shows that Carm1 affects cell fate by promoting asymmetric divisions, that direct one daughter cell inside, and cell engulfment, where neighboring cells with lower Carm1 levels compete for outside positions. This is associated with changes to the expression pattern and spatial distribution of cell polarity proteins: Cells with higher Carm1 levels show reduced expression and apical localization of Par3 and a dramatic increase in expression of PKCII, antagonist of the apical protein aPKC. Expression and basolateral localization of the mouse Par1 homologue, EMK1, increases concomitantly. Increased Carm1 also reduces Cdx2 expression, a transcription factor key for TE differentiation. These results demonstrate how the extent of a specific epigenetic modification could affect expression of cell polarity and fate-determining genes to ensure lineage allocation in the mouse embryo.