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蛋白质编码基因中的H3K9me3-异染色质损失使发育谱系的规范成为可能

Dario Nicetto^1,2,3, Greg Donahue^1,2,3, Tanya Jain^1,2,3

¹Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Science (New York, N.Y.)

|January 5, 2019

概括

在胚胎发育过程中,由H3K9me3标记的染色体紧缩是动态调节的. 这项研究揭示了它在细胞命运决策和血统承诺中的关键作用.

科学领域:

表观遗传学和基因调控
发育生物学
染色体生物学

背景情况:

通过染色质紧缩抑制基因对于细胞命运的确定至关重要.
由三甲基化素H3素9 (H3K9me3) 标记的异质染色体从胚胎干细胞减少到分化的细胞.
在胚胎发育过程中,蛋白质编码基因的闭合色素区域的动态尚不清楚.

研究的目的:

在早期胚胎发育过程中研究蛋白质编码基因中压缩异色素的建立和动态.
描述H3K9me3标记的异染色体在细胞系结合和维持中的作用.

主要方法:

开发一种抗体独立的方法,从低细胞数量样本中分离和绘制压缩的异性染色体.
在胚胎层发育和分化过程中分析H3K9me3在蛋白质编码基因中的分布.
与H3K9me3相关的甲基转移酶的干扰,以评估它们的功能影响.

主要成果:

在早期未结合的生殖层细胞中发现了高水平的紧,H3K9me3装饰的异染色体.
在分化过程中,压缩的异性染色体经历了显著的重新排列和减少,与细胞类型特定的基因表达相关.
H3K9me3甲基转移酶的干扰破坏了谱系的承诺和保持谱系的忠实性.

结论:

在早期胚胎发育过程中,标记为H3K9me3的异染色体在调节基因表达方面发挥着关键作用.
这种表观遗传标记对于在器官生成开始时的血统承诺和维持细胞类型完整性至关重要.

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