远端增强剂通过长距离相互作用来调节哺乳动物早期胚胎血统的分化
Qianshu Zhu1, Shimeng Guo1, Juan Xie1
1Chongqing Key Laboratory of Human Embryo Engineering and Precision Medicine, Center for Reproductive Medicine, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, Chongqing 400013, China.
Nucleic acids research
|January 21, 2026
概括
在远端增强剂的基因组H3 lysine 27乙化 (H3K27ac) 驱动早期胚胎细胞分化. 这种表观遗传标记,而不仅仅是可访问性,对于特定基因表达和发展至关重要.
科学领域:
- 发展生物学 发展生物学
- 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:
- 基质子修饰调节细胞分化,但H3K27ac和染色质结构在早期胚胎血统 (TE和ICM) 中的作用尚不清楚.
- 了解这些因素是解读植入前发育机制的关键.
研究的目的:
- 调查H3K27ac和更高阶染色体结构在TE和ICM谱系规范中的作用.
- 确定关键的调节者和机制,控制从毛囊到胚胎细胞的过渡.
主要方法:
- 在TE和ICM中对H3K27ac,染色质可访问性和转录组进行超低输入多omics分析.
- 整合多主题数据以识别监管元素和转录因子结合.
- 对增强剂-促进剂循环的分析和关键蛋白的功能验证 (BRD4,p300,YY1).
主要成果:
- H3K27ac富含远端增强剂,在早期分化过程中驱动谱系特定基因表达.
- 确定了特定于血统的增强剂-促进剂循环,涉及BRD4,p300和YY1,这对于Morula-to-blastocyst过渡至关重要.
- 抑制CBP/p300干扰了H3K27ac增强剂,降低了与胎盘相关的基因的下调,突出了H3K27ac在可访问性之外的作用.
结论:
- 标记为H3K27ac的远端增强剂通过通过长距离色素相互作用促进基因表达,对早期血统分化至关重要.
- 在TE和ICM中,增强器活动需要H3K27ac的获取,而不仅仅是可访问性.
- 跨物种比较显示TE增强剂中保存的H3K27ac模式,强调它们在哺乳动物胚胎发育中的基本作用.
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