Li Feifei, Wan Mian, Zhang Binpeng, Peng Yiran, Zhou Yachuan, Pi Caixia, Xu Xin, Ye Ling, Zhou Xuedong, Zheng Liwei
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
West China School of Stomatology, Sichuan University, Chengdu, China.
Curr Stem Cell Res Ther. 2018;13(2):83-90. doi: 10.2174/1574888X12666170123144743.
Development is an epigenetic regulation dependent event. As one pretranscriptional regulator, bivalent histone modifications were observed to be involved in development recently. It is believed that histone methylation potentially takes charge of cell fate determination and differentiation. The synchronous existence of functionally opposite histone marks at transcript start sequence (TSS) is defined as "Bivalency", which mainly mark development related genes. H3K4me3 and H3K27me3, the prominent histone methylations of bivalency, are implicated in transcriptional activation and transcriptional repression respectively. The delicate balance between H3K4me3 and H3K27me3 produces diverse chromatin architectures, resulting in different transcription states of downstream genes: "poised", "activated" or "repressed".
In order to explore the developmental role of bivalent histone modification and the underlying mechanism, we did systematic review and rigorous assessment about relative literatures.
Bivalent histone modifications are considered to set up genes for activation during lineage commitment by H3K4me3 and repress lineage control genes to maintain pluripotency by H3K27me3. Summarily, bivalency in stem cells keeps stemness via poising differentiation relevant genes. After receiving developmental signals, the balance between "gene activation" and "gene repression" is broken, which turns genes transcription state from "poised" effect to switch on or switch off effect, thus initiates irreversible and spontaneous differentiation procedures.
Bivalent histone modifications and the associated histone-modifying complexes safeguard proper and robust differentiation of stem cells, thus playing an essential role in development.
发育是一个依赖表观遗传调控的过程。作为一种转录前调节因子，二价组蛋白修饰最近被发现参与发育过程。据信，组蛋白甲基化可能负责细胞命运的决定和分化。转录起始序列（TSS）上功能相反的组蛋白标记同步存在被定义为“双价性”，主要标记与发育相关的基因。H3K4me3和H3K27me3是双价性的主要组蛋白甲基化修饰，分别与转录激活和转录抑制有关。H3K4me3和H3K27me3之间的微妙平衡产生了不同的染色质结构，导致下游基因呈现不同的转录状态：“就绪”、“激活”或“抑制”。
为了探讨二价组蛋白修饰在发育中的作用及其潜在机制，我们对相关文献进行了系统回顾和严格评估。
二价组蛋白修饰被认为通过H3K4me3在谱系定向过程中为基因激活做好准备，并通过H3K27me3抑制谱系控制基因以维持多能性。总之，干细胞中的双价性通过使与分化相关的基因处于就绪状态来维持干性。在接收到发育信号后，“基因激活”和“基因抑制”之间的平衡被打破，从而使基因转录状态从“就绪”效应转变为开启或关闭效应，进而启动不可逆的自发分化过程。
二价组蛋白修饰及相关的组蛋白修饰复合物保障了干细胞的正常和稳健分化，因此在发育中起着至关重要的作用。
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