空间基因组组织的广泛异质性和内在变异
Elizabeth H Finn1, Gianluca Pegoraro2, Hugo B Brandão3
1National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Cell
|February 26, 2019
概括
细胞3D基因组组织显示出显著的变异性. 个别的等位基因独立地表现,在细胞群中显示出广泛的基因组配置.
科学领域:
- 基因组学和分子生物学
- 细胞生物学
- 表观遗传学
背景情况:
- 3D基因组组织的确立原则包括非随机染色体定位,染色体区和拓关联域 (TAD).
- 然而,基因组结构中的细胞对细胞和细胞内在变异性仍然不太清楚.
研究的目的:
- 在单细胞水平上系统地调查和描述3D基因组组织的异质性.
- 了解人类纤维细胞群中的基因组结构变异性的程度和性质.
主要方法:
- 使用高通量光学映射分析了几百个人类纤维细胞中的染色体内相互作用.
- 使用单细胞分析来检查单核中的单个等位基因的行为.
主要成果:
- 由基因组距离,高阶染色体结构和染色体环境影响的低染色体内关联频率.
- 单个细胞之间的拓关联域 (TAD) 结构的变异性,具有共同的TAD之间的关联.
- 在单个核中展示单个基因的独立行为,突出显著的异质性.
结论:
- 这项研究揭示了个别基因水平上的3D基因组组织的广泛变异性和异质性.
- 一种广泛的基因组配置在细胞群体内共存,挑战了静态基因组架构的概念.
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