Oct-4 controls cell-cycle progression of embryonic stem cells

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Mouse and human ES (embryonic stem) cells display unusual proliferative properties and can produce pluripotent stem cells indefinitely. Both processes might be important for maintaining the 'stemness' of ES cells; however, little is known about how the cell-cycle fate is regulated in ES cells. Oct-4, a master switch of pluripotency, plays an important role in maintaining the phuripotent state of ES cells and may prevent the expression of genes activated during differentiation. Using ZHBTc4 ES cells, we have investigated the effect of Oct-4 oil ES cell-cycle control, and we found that Oct-4 down-regulation in ES cells inhibits proliferation by blocking cell-cycle progression in G(0)/G(1). Deletion analysis of the functional domains of Oct-4 indicates that the overall integrity of the Oct-4 functional domains is important for the stimulation of S-phase entry. We also show in the present study that the p21 gene is a target for Oct-4 repression. Furthermore, p21 protein levels were repressed by Oct-4 and were induced by the down-regulation of Oct-4 in ZHBTc4 ES cells. Therefore the down-regulation of p21 by Oct-4 may contribute to the maintenance of ES cell proliferation.
Publisher
PORTLAND PRESS LTD
Issue Date
2010-03
Language
English
Article Type
Article
Keywords

TRANSCRIPTION FACTOR OCT-4; POU-DOMAIN; SELF-RENEWAL; GERM-LINE; EXTRAEMBRYONIC MEMBRANES; MAMMALIAN EMBRYO; ES CELLS; EXPRESSION; GENE; BINDING

Citation

BIOCHEMICAL JOURNAL, v.426, no.2, pp.171 - 181

ISSN
0264-6021
DOI
10.1042/BJ20091439
URI
http://hdl.handle.net/10203/97429
Appears in Collection
BS-Journal Papers(저널논문)
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