中科院上海生命科學院,、上海交大醫(yī)學院健康科學研究所研究員金穎教授帶領的研究小組將在最新一期的Journal of Biological Chemistry上發(fā)表研究成果。文章標題為：Critical roles of coactivator p300 in mouse embryonic stem cell differentiation and nanog expression.
胚胎干細胞(ES cells)來源于植入前胚胎囊胚期的內細胞團，具有自我更新和全能性的特點,。ES細胞的自我更新和全能性特性是由細胞外信號分子和細胞內的關鍵轉錄因子共同調控的，如Oct4和Nanog等,。p300是一個具有組蛋白乙酰轉移酶活性的轉錄共激活因子,，它在胚胎發(fā)育和很多生理過程中都發(fā)揮著重要的作用。但是,，p300對ES細胞的全能性維持和分化過程是否具有調控功能,，目前為止還沒有研究報道過。
在金穎研究員的指導下,，健康所發(fā)育生物學實驗室博士生鐘小敏同學對p300在小鼠ES細胞中的功能進行了探索,。研究發(fā)現(xiàn)，在自我更新能力和全能性分子標志的表達水平上,，p300基因敲除的小鼠胚胎干細胞與野生型ES細胞沒有任何區(qū)別,。但是在體外誘導分化時，p300的缺失使ES細胞向內中外三個胚層的分化發(fā)生了異常,，并且該表型可以部分地被Nanog基因的外源過量表達所恢復,。通過對Nanog基因轉錄調控的分析和研究,，p300被證明可以直接結合在Nanog基因的轉錄調控區(qū)并調節(jié)其表達。進一步的研究表明,，p300調控Nanog基因表達的機制可能與組蛋白的乙?；揎椕芮邢嚓P。
該研究工作首次證明了p300在ES細胞分化過程中的作用及其對Nanog基因的表達調控功能,，為以后進一步闡明ES細胞分化的機制以及Nanog基因的作用提供了參考,。這項研究工作于2009年4月發(fā)表在《生物化學雜志》 (The Journal of Biological Chemistry)上。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
