来自美国卡耐基科学研究所的Yixian Zheng实验室发现通过遗传学上阈值的调节和mRNA的修饰作用维持ESCs的多潜能和自我更新调节,本篇文章刊登在最新一期《CELL》杂志上。

-2012年10月26日《细胞》


中文翻译


【题目】胚胎干细胞自我更新的机制

【译文】胚胎干细胞多潜能性需要对主要发育基因的二价染色体进行后天修饰,这些发育基因受到各种转录因子和染色质修饰酶的调节。这些因子是如何与其他二个协作来维持二价染色体稳定从而使得ESCs可以进行快速的自我更新同时维持多潜能性都不得而知。我们发现Utf1是Oct4和Sox2a的目标之一,它是二价染色质的组成之一并且可以稳定二价基因。Utf1通过限制PRC2的加载和组蛋白3的27位赖氨酸的三甲基化,对二价基因设定合适的激活阈值。它也可以促进mRNAs的核标记,这些mRNAs是由没有被沉默的二价基因转录的,这些mRNAs通过脱盖作用来形成细胞质的降解作用。Utf1这些相反的作用促进了协调的分化。mRNA的降解作用也通过抑制Myc-Arf反馈调节来确保快速的细胞增殖作用。因此,Utf1偶联了中心多潜能因子与Myc和PRC2网络一起促进ESCs的多潜能和增殖作用。

英文原稿


[Title]Regulation of Pluripotency and Self- Renewal of ESCs through Epigenetic- Threshold Modulation and mRNA Pruning

[Authors]Junling Jia, Xiaobin Zheng, Gangqing Hu, Kairong Cui, Junqi Zhang, Anying Zhang, Hao Jiang, Bingwen Lu, John Yates, Chengyu Liu, Keji Zhao, Yixian Zheng

[Abstract]Embryonic stem cell (ESC) pluripotency requires bivalent epigenetic modifications of key developmental genes regulated by various transcription factors and chromatin-modifying enzymes. How these factors coordinate with one another to maintain the bivalent chromatin state so that ESCs can undergo rapid self-renewal while retaining pluripotency is poorly understood. We report that Utf1, a target of Oct4 and Sox2, is a bivalent chromatin component that buffers poised states of bivalent genes. By limiting PRC2 loading and histone 3 lysine-27 trimethylation, Utf1 sets proper activation thresholds for bivalent genes. It also promotes nuclear tagging of messenger RNAs (mRNAs) transcribed from insufficiently silenced bivalent genes for cytoplasmic degradation through mRNA decapping. These opposing functions of Utf1 promote coordinated differentiation. The mRNA degradation function also ensures rapid cell proliferation by blocking the Myc-Arf feedback control. Thus, Utf1 couples the core pluripotency factors with Myc and PRC2 networks to promote the pluripotency and proliferation of ESCs.

原文地址

http://www.cell.com/abstract/S0092-8674(12)01167-1

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