由YY1调解的动态核细胞重塑是小鼠早期发育的基础.
Mizuki Sakamoto1, Shusaku Abe2, Yuka Miki2
1Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi 400-8510, Japan.
Genes & development
|August 2, 2023
概括
早期小鼠胚胎中的核细胞组织从异位细胞中模糊的转变为明确的转变,转录因子YY1驱动了这种对发育至关重要的表观遗传重塑.
科学领域:
- 表观遗传学和发育生物学
- 染色素的结构和动力学
- 哺乳动物胚胎发生
背景情况:
- 核细胞的定位对于调节DNA可访问性和基因表达是至关重要的,影响细胞的身份.
- 早期哺乳动物发育涉及动态基因表达和细胞功率的变化,这意味着表观遗传调节.
- 在植入前的发育过程中,核细胞组织的精确动态在很大程度上仍然没有被描述.
研究的目的:
- 研究在小鼠胚胎早期发育过程中核细胞组织的动态.
- 为了确定核细胞定位观察到的变化背后的机制.
- 了解YY1等特定因素在发育过程中建立染色质结构中的作用.
主要方法:
- 利用低输入的微球菌核酶测序 (MNase-seq) 方法来描述核细胞位.
- 研究了染色质组装对核细胞组织的影响,通过对胚胎干细胞中的下调组分进行调节.
- 在八细胞胚胎中确定了转录因子结合位 (YY1) 并分析了相关的表观遗传修饰.
主要成果:
- 核细胞的定位在异构体中是全局模糊的,并在后来的胚胎阶段得到了很好的定义.
- 染色体组合因子的下调部分恢复了类似细胞胞的核细胞体模式.
- 转录因子YY1被确定为调控元素中的de novo核细胞组阵形成的关键调节者.
- 与YY1结合的区域显示H3K27ac的丰富,而YY1的枯竭破坏了Morula-to-blastocyst的过渡.
结论:
- 核细胞组织在小鼠早期发育过程中经历了显著的重塑,从"模糊"状态过渡到定义状态.
- 染色体组装途径和转录因子YY1对于在胚胎发生过程中建立良好位置的核细胞体至关重要.
- 通过对核细胞组织的影响,YY1在调节基因可访问性和发育进展方面发挥着关键作用.
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