3D增强器-促进器网络提供了早期胚胎血统中基因表达和共同调节的预测特征
Dylan Murphy1,2, Eralda Salataj1, Dafne Campigli Di Giammartino1,3
1Sanford I. Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Nature structural & molecular biology
|December 5, 2023
概括
这项研究揭示了3D染色质结构和增强剂如何指导早期哺乳动物发育. 关键的调控中心控制基因表达和细胞身份在新生胚胎血统.
科学领域:
- 发展生物学 发展生物学
- 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.
背景情况:
- 哺乳动物胚胎发生涉及到关键的细胞命运决定,形成肌体内皮,表皮质和原始内皮.
- 控制这些早期命运的非编码性监管要素尚未得到充分研究.
研究的目的:
- 描述早期哺乳动物系的全基因组增强剂活性和3D染色质连接性.
- 了解3D调控架构在特定基因表达中的作用.
主要方法:
- 在胚胎衍生干细胞中对增强剂活性和3D染色质连接性的全基因组分析.
- 开发和应用一个包含3D染色体特征的预测模型 (3D-HiChAT).
- 克里斯普尔干扰 (CRISPRi) 用于对候选增强剂进行实验验证.
主要成果:
- 在三种谱系中观察到广泛的增强器重塑和3D染色体重新连接,与转录变化相关.
- 在3D染色体结构中,高连接性与基因表达水平和基本基因有关.
- 整合3D染色体数据的预测模型 (3D-HiChAT) 优于1D模型来预测基因表达.
结论:
- 三维调节枢纽对于在最早的哺乳动物血统中建立和维持细胞身份至关重要.
- 了解3D染色体组织为破译谱系特异性转录调节提供了一个框架.
- 经过验证的候选增强剂证明了3D监管元素在开发中的功能重要性.
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