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在胚胎干细胞中系统识别病毒沉默因子

Bin Xia Yang¹, Chadi A El Farran², Hong Chao Guo³

¹Epigenetics and Cell Fates Laboratory, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore.

|September 15, 2015

概括

胚胎干细胞 (ESCs) 使用基因组辅助子,化因子和染色体修饰剂来抑制逆转录病毒. 这项研究揭示了细胞关键因素和表观遗传机制,这些因素对ESC中前病毒DNA抑制至关重要.

科学领域:

表观遗传学
分子生物学
基因组学

背景情况:

胚胎干细胞 (ESC) 具有抑制外源性前病毒和内源性逆病毒 (ERV) 表达的独特能力.
了解控制这种沉默的细胞机制对于理解基因组稳定性和发育过程至关重要.

研究的目的:

系统地识别和描述胚胎癌 (ECs) 和ESCs中对前病毒抑制负责的细胞因素.
在多能性背景下阐明背后的遗传和表观遗传机制.

主要方法:

全基因组 siRNA 查以确定涉及前病毒沉默的关键细胞因素.
用RNA测序 (RNA-seq) 来分析已识别的因素对ERV表达的影响.
染色体免疫沉,然后进行测序 (ChIP-seq),以确定直接招募因子到ERV.

主要成果:

鉴定出 histone chaperones (Chaf1a/b),sumoylation因子 (例如,Sumo2) 和染色体修饰剂 (例如,Trim28) 是对前病毒沉默至关重要的.
在抑制ERV方面,Chaf1a/b和化修饰剂起着重要作用,直接将Chaf1a和Sumo2招募到ERV位点.
Chaf1a与NuRD复合体和Eset相互作用,而Sumo2则修改了Trim28,加强了Zfp809/Trim28/Eset沉默通路.

结论:

这项研究提供了在ESC中调解前病毒沉默的功能节点的综合基因组图谱.
它揭示了ESC维持逆转录病毒抑制的相互关联的多层遗传和表观遗传机制.
这些发现突显了染色体修饰剂和表观遗传调节剂在保护基因组免受逆转录病毒因素的复杂相互作用.

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相关概念视频

Embryonic Stem Cells

Embryonic Stem Cells

Embryonic stem (ES) cells are undifferentiated pluripotent cells, meaning they can produce any cell type in the body. This gives them tremendous potential in science and medicine since they can generate specific cell types for use in research or to replace body cells lost due to damage or disease.

Embryonic Stem Cells

Embryonic Stem Cells

Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...