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染色体组织在早期胚胎形成中的亲子转移
Samuel Collombet1,2, Noémie Ranisavljevic1,3, Takashi Nagano4,5
1Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, UPMC Paris-Sorbonne, Paris, France.
Nature
|April 3, 2020
概括
早期胚胎发育涉及3D基因组组织的动态变化. 父母基因组建立了与基因调节相关的独特结构,同时出现了具有活跃基因的新领域,影响了发育.
科学领域:
- 发育生物学
- 表观遗传学
- 基因组学
背景情况:
- 父亲和母亲的表观基因组在受精后经历了显著的重塑.
- 之前的研究表明,关于配体和早期胚胎中拓相关域 (TAD) 的存在和时间存在矛盾的结论.
- 父母染色体结构的遗传及其在等位基因特异性基因调节中的作用尚不清楚.
研究的目的:
- 在小鼠植入前发育过程中绘制家长基因组相互作用.
- 研究3D基因组组织,等位基因特异性基因表达和染色体标记之间的关系.
- 了解X染色体无活化过程中的TAD动态.
主要方法:
- 使用优化的单细胞高通量染色体构造捕获 (Hi-C) 协议.
- 综合染色体组织数据与基表达状态和基因组修饰.
- 在X染色体无活化过程中分析了父X染色体的结构变化.
主要成果:
- 在受精后,更高层次的染色体结构显示H3K27甲基化的等位基因特异丰富,与基因抑制和父母印记相关.
- 在第二波基因组组合期间,与活性染色体相关的非父母特异性TADs出现.
- 在父X染色体基因沉默过程中,TADs会消失,但在逃脱不活化的区域内会持续存在.
结论:
- 早期的父母特异性域在父母偏向的基因表达和印记中起作用.
- 新的TAD以非父母特异的方式建立,并与活跃的基因表达有关.
- 3D基因组组织动态对于早期发育过程中的基因表达调节至关重要,包括X染色体的失活.
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