在早期随机X染色体失活过程中解决了4D染色体动力学
Xiaowen Liu1,2, Hao Xie1, Zhiyuan Liu1,3
1Biomedical Pioneering Innovation Center (BIOPIC) and School of Life Sciences, Peking University, Beijing 100871, China.
Genomics, proteomics & bioinformatics
|January 13, 2026
概括
X染色体不活化涉及显著的3D重组. 新的HiRES多组学揭示了在雌性哺乳动物的这一关键过程中伴随基因沉默的短暂状态和染色质变化.
科学领域:
- 遗传学和基因组学 在
- 表观遗传学和染色体生物学
- 发展生物学 发展生物学
背景情况:
- 在雌性哺乳动物中,X染色体无活化 (XCI) 对于剂量补偿至关重要.
- XCI涉及到广泛的三维 (3D) 染色质重组.
- 了解早期XCI阶段的动态仍然具有挑战性.
研究的目的:
- 在XCI早期阶段调查四维 (4D) 染色质动态.
- 描述单细胞无活化轨迹和相关的染色质重塑.
- 阐明XCI启动中的Xist表达的作用.
主要方法:
- 应用HiRES (Hi-C和RNA-seq同时进行) 多omics测序.
- 对接受诱导随机XCI的小鼠胚胎干细胞的分析.
- 3D基因组和转录组的单细胞分辨率.
主要成果:
- 在单细胞分辨率下确定了不同的无活化轨迹.
- 在双基X表达过程中发现了X染色体在双基X表达过程中共享的短暂结构状态.
- 证明大多数染色体重塑伴随或遵循基因沉默.
- 揭示了拓关联域 (TAD) 衰减始于相互作用损失.
结论:
- 提供了XCI启动过程中染色质重组的详细,细度描绘.
- 强调了3D基因组结构和基因沉默之间的动态相互作用.
- 确立了HiRES作为研究动态多omics过程的强大工具.
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