超分辨率的染色体追踪揭示了单个细胞中的域和合作相互作用
Bogdan Bintu1, Leslie J Mateo2, Jun-Han Su1
1Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology and Department of Physics, Harvard University, Cambridge, MA 02138, USA.
Science (New York, N.Y.)
|October 27, 2018
概括
这项研究引入了一种高分辨率的成像技术,可视化单个细胞中的染色质组织,揭示动态的细胞特异性结构,如拓关联域 (TAD) 和它们的边界,独立于凝聚素水平.
科学领域:
- 基因组学
- 细胞生物学
- 分子生物学
背景情况:
- 染色体的空间组织对于调节基因表达和基因组稳定性至关重要.
- 拓关联域 (TAD) 是关键的结构单元,但它们在单个细胞中的形成和动态仍然不完全理解.
研究的目的:
- 开发和应用一种高分辨率的成像方法,以在数千个单个细胞中可视化基基和纳米尺度的染色体组织.
- 研究染色体的单细胞构造,包括TAD及其边界,以及凝聚素在它们的形成中的作用.
主要方法:
- 开发一种用于追踪染色体组织的新型成像技术.
- 在成千上万个单个细胞的拓关联域 (TAD) 中分析染色体构造.
- 对凝聚素减少对TAD结构和染色体相互作用的影响的评估.
主要成果:
- 在单个细胞中发现具有球状构造和利边界的TAD类结构,边界位置具有细胞间的变异.
- 在CCCTC结合因子 (CTCF) 和凝聚结合点确定了优选边界位置.
- 证明凝聚素消耗取消了人口平均TAD,但保留了单细胞TAD样结构,同时消除了优选的边界区域.
- 观察到广泛的,合作的,多途径的染色体相互作用,在凝聚素耗尽后持续存在.
结论:
- 单细胞成像为染色体组织的动态性提供了关键的见解,揭示了细胞特异性TAD和边界形成机制.
- 凝聚素在确定偏好的边界位置方面发挥作用,但对于单个细胞中的TAD类结构来说并不必不可少.
- 广泛的染色体相互作用是独立于凝聚素的,这表明了更高阶染色体组织的替代机制.
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