在经过重编程的单个人类细胞中剖析基因激活和染色质重塑动态
Jose A Martinez-Sarmiento1, Maria Pia Cosma2, Melike Lakadamyali3
1Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
Cell reports
|May 3, 2024
概括
细胞重编程涉及染色质变化和基因激活. 这项研究揭示了多能转化过程中染色质开放和转录的基因特异时间,突出了依赖上下文的动态.
科学领域:
- 细胞生物学 细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因组学就是基因组学.
背景情况:
- 细胞命运过渡涉及复杂的分子重塑.
- 在单细胞水平上理解这些变化的时间动态是具有挑战性的.
- 异质核子介导的重编程为研究早期多能转换提供了一个模型.
研究的目的:
- 剖析早期多能转换期间染色质和基因表达变化的时间动态.
- 在单细胞中研究染色体重塑和基因激活之间的因果关系.
- 在异质子系统中利用超高分辨率成像来观察这些事件.
主要方法:
- 作为单细胞模型的异质细胞介导重编程.
- 超高分辨率成像可视化分子事件.
- 分析了基因组修饰 (H3K9me3,H3K27me3,H3K4me3,H3K9ac) 和基因转录 (OCT4,NANOG) 的情况.
主要成果:
- 身体核在全球分解染色质,并在融合后失去抑制性基因素标记 (H3K9me3,H3K27me3).
- OCT4 (POU5F1) 转录在没有初始位置开放的24小时内开始.
- NANOG转录在48小时开始,先后在基因组的位置重新开放.
- 在早期的重编程阶段,活跃的基因素标记不会立即获得.
结论:
- 染色体变化和基因激活之间的时间关系在重新编程过程中是基因特异性的.
- 早期的染色体分解并不总是先于基因激活.
- 细胞重编程涉及不同多能基因的独特时间程序.
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