Critical Roles of Coactivator p300 in Mouse Embryonic Stem Cell Differentiation and Nanog Expression

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摘要：

p300 is a well known histone acetyltransferase and coactivator that plays pivotal roles in many physiological processes. Despite extensive research for the functions of p300 in embryogenesis and transcription regulation, its roles in regulating embryonic stem (ES) cell pluripotency are poorly understood. To address this issue, we investigated the self-renewal ability and early differentiation process in both wild-type mouse ES cells and ES cells derived from knock-out () mice. We found that ablation did not affect self-renewal capacity overtly when ES cells were maintained under undifferentiated conditions. However, the absence of caused a significantly abnormal expression pattern of germ layer markers when differentiation was induced by embryoid body (EB) formation. Interestingly, the expression level of pluripotency marker but not was markedly lower in EBs from ES cells compared with that in EBs from wild-type ES cells. Exogenous expression of rescued abnormal expression of extra-embryonic endoderm marker partially but not mesoderm and ectoderm markers. Furthermore, we demonstrate that p300 was directly involved in modulating expression. Importantly, epigenetic modification of histone acetylation at the distal regulatory region of was found to be dependent on the presence of p300, which could contribute to the mechanism of regulating expression by p300. Collectively, our results show that p300 plays an important role in the differentiation process of ES cells and provide the first evidence for the involvement of p300 in regulating expression during differentiation, probably through epigenetic modification of histone on .

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DOI：

10.1074/jbc.M805562200

被引量：

137

年份：

2009