Cell cycle and developmental regulations of replication factors in mouse embryonic stem cells
Cell cycle and developmental regulations of replication factors in mouse embryonic stem cells
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DOI：
10.1074/jbc.m412224200
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发表时间：
2005-04-01
影响因子：
4.8
通讯作者：
Masai, H
中科院分区：
文献类型：
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作者：
Fujii-Yamamoto, H;Kim, JM;Masai, H
胚胎干细胞（ES细胞）可以快速和永久地生长，同时保持其分化能力。为了深入了解未分化小鼠ES细胞的细胞周期进程是如何调节的，我们研究了各种复制和细胞周期调节因子的表达模式。大多数因子，包括细胞周期蛋白，Cdc6，和geminin相当组成型表达在ES细胞的细胞周期。此外，几乎所有的细胞周期调节因子，我们调查除了p21和p27的转录水平高于未分化的ES细胞比小鼠胚胎成纤维细胞（MEFs），和增加的稳定性的mRNA在ES细胞可能是部分负责这至少与一些因素。更引人注目的是，这些因子的转录水平与组蛋白H3在其启动子区域的乙酰化状态密切相关。然而，组蛋白的甲基化状态或启动子区域的CpG甲基化通常与这两种细胞类型中这些因子的表达模式不显著相关。在蛋白质水平上，Cdc6、ASK、细胞周期蛋白A2和细胞周期蛋白B1在ES细胞中与MEFs相比是极其丰富的。此外，它们在诱导ES细胞分化时迅速下调。这些研究结果的意义进行了讨论有关的不寻常的增殖特性的ES细胞在未分化状态。
Embryonic stem (ES) cells can grow rapidly and permanently while maintaining their differentiation capacity. To gain insight into how the cell cycle progression of undifferentiated murine ES cells is regulated, we have examined the expression patterns of various replication and cell cycle regulators. Most factors including cyclins, Cdc6, and geminin are rather constitutively expressed during the cell cycle of ES cells. Furthermore, the transcript levels of almost all the cell cycle regulators we investigated except for p21 and p27 are higher in undifferentiated ES cells than in murine embryonic fibroblasts ( MEFs), and the increased stability of mRNA in ES cells may be partially responsible for this at least with some of the factors. More strikingly, the transcriptional levels of these factors are strongly correlated with the acetylated state of histone H3 at their promoter regions. However, the methylation state of histone or CpG methylation of the promoter region is not generally correlated significantly with the expression pattern of these factors in both cell types. On the protein level, Cdc6, ASK, cyclin A2, and cyclin B1 are extremely abundant in ES cells compared with MEFs. Furthermore, they are rapidly down-regulated upon induction of differentiation of ES cells. The significance of these findings is discussed in relation to the unusual proliferative properties of ES cells in an undifferentiated state.