中科院上海生命科学院、上海交大医学院健康科学研究所研究员金颖教授带领的研究小组将在最新一期的Journal of Biological Chemistry上发表研究成果。文章标题为：Critical roles of coactivator p300 in mouse embryonic stem cell differentiation and nanog expression.
胚胎干细胞(ES cells)来源于植入前胚胎囊胚期的内细胞团，具有自我更新和全能性的特点。ES细胞的自我更新和全能性特性是由细胞外信号分子和细胞内的关键转录因子共同调控的，如Oct4和Nanog等。p300是一个具有组蛋白乙酰转移酶活性的转录共激活因子，它在胚胎发育和很多生理过程中都发挥着重要的作用。但是，p300对ES细胞的全能性维持和分化过程是否具有调控功能，目前为止还没有研究报道过。
在金颖研究员的指导下，健康所发育生物学实验室博士生钟小敏同学对p300在小鼠ES细胞中的功能进行了探索。研究发现，在自我更新能力和全能性分子标志的表达水平上，p300基因敲除的小鼠胚胎干细胞与野生型ES细胞没有任何区别。但是在体外诱导分化时，p300的缺失使ES细胞向内中外三个胚层的分化发生了异常，并且该表型可以部分地被Nanog基因的外源过量表达所恢复。通过对Nanog基因转录调控的分析和研究，p300被证明可以直接结合在Nanog基因的转录调控区并调节其表达。进一步的研究表明，p300调控Nanog基因表达的机制可能与组蛋白的乙酰化修饰密切相关。
该研究工作首次证明了p300在ES细胞分化过程中的作用及其对Nanog基因的表达调控功能，为以后进一步阐明ES细胞分化的机制以及Nanog基因的作用提供了参考。这项研究工作于2009年4月发表在《生物化学杂志》 (The Journal of Biological Chemistry)上。（生物谷Bioon.com）
生物谷推荐原始出处：
J. Biol. Chem, 10.1074/jbc.M805562200
Critical roles of coactivator p300 in mouse embryonic stem cell differentiation and nanog expression
Xiaomin Zhong and Ying Jin
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai, Shanghai 200025
p300 is a well-known histone acetyltransferase and coactivator playing pivotal roles in many physiological processes. Despite extensive research for 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 p300 knock-out (p300-/-) mice. We found that p300 ablation did not affect self-renewal capacity overtly when ES cells were maintained under undifferentiated conditions. However, the absence of p300 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 Nanog, but not Oct4, was markedly lower in EBs from p300-/- ES cells, compared to that in EBs from wild-type ES cells. Exogenous expression of Nanog 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 Nanog expression. Importantly, epigenetic modification of histone acetylation at the distal regulatory region of Nanog was found to be dependent on the presence of p300, which could contribute to the mechanism of regulating Nanog 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 involvement of p300 in regulating Nanog expression during differentiation, probably through epigenetic modification of histone on Nanog.
