Cell cycle and developmental regulations of replication factors in mouse embryonic stem cells

被引:89
|
作者
Fujii-Yamamoto, H
Kim, JM
Arai, K
Masai, H
机构
[1] Tokyo Metropolitan Inst Med Sci, Dept Cell Biol, Bunkyo Ku, Tokyo 1138613, Japan
[2] Tokyo Metropolitan Inst Med Sci, Dept Integrat Life Sci, Bunkyo Ku, Tokyo 1138613, Japan
[3] Univ Tokyo, Grad Sch Med, Dept Biochem & Mol Biol, Bunkyo Ku, Tokyo 1130033, Japan
关键词
D O I
10.1074/jbc.M412224200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:12976 / 12987
页数:12
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