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通过从TRIM28抑制中逃脱的基因来选择内源逆转录病毒
Rocio Enriquez-Gasca1, Poppy A Gould1, Hale Tunbak1
1Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London E1 2AT, UK.
Cell reports
|June 9, 2023
概括
选择性内源逆转录病毒 (ERVs) 来自遗传"逃脱"中,这些遗传"逃脱"失去了沉默和逆转换的序列. 这些逃逸物可以在细胞分化过程中激活附近的神经基因.
科学领域:
- 基因组学就是基因组学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 发展生物学 发展生物学
背景情况:
- 内源逆转录病毒 (ERV) 是集成的病毒序列,可以影响宿主基因调节.
- 对于ERV被吸收到宿主基因网络中的机制尚不完全了解.
- 细胞分化涉及基因表达和表观遗传景观的重大变化.
研究的目的:
- 调查细胞分化过程中ERV选择的起源.
- 为了确定涉及转录调节和逃避沉默的特定ERV序列.
- 了解ERV如何影响神经前代细胞中的基因表达.
主要方法:
- 利用活跃的小鼠ERV,IAPEz和胚胎干细胞 (ESC) 到神经原生细胞 (NPC) 差异化模型.
- 研究了TRIM28和表观遗传标记 (H3K9me3,H3K27me3) 介导的转录沉默机制.
- 分析了"逃逸"ERV中的序列分歧,并验证了特定LTR序列的增强器功能.
主要成果:
- 确定了一种190bp序列,该序列编码了TRIM28介导的沉默和逆转换所必需的内A型粒子 (IAP) 信号.
- 发现IAP的一个子集 ("逃脱") 呈现遗传分歧,逃避TRIM28和表观遗传抑制 (H3K9me3,H3K27me3).
- 证明逃生IAPs在NPC中被转录失压,并具有增强剂活性,通过47bp的LTR序列激活附近的神经基因.
结论:
- 同选ERVs来自遗传逃生,这些遗传逃生已经失去了TRIM28限制和逆转换的关键序列.
- 特别是在逃生变体中,ERV增强器功能在分化过程中在宿主基因网络的重新连接中发挥作用.
- 这些发现为ERV的进化动态及其对宿主基因组进化的贡献提供了洞察力.
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