识别用于哺乳动物DNA复制的空间时间控制的cis元素
Jiao Sima1, Abhijit Chakraborty2, Vishnu Dileep1
1Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
Cell
|January 1, 2019
概括
离散的cis-regulatory元素,称为早期复制控制元素 (ERCE),编排DNA复制时间,基因组架构和转录. 这些元素对于链接基因组结构和功能至关重要.
科学领域:
- 基因组学
- 分子生物学
- 表观遗传学
背景情况:
- 复制时间 (RT) 与基因组架构有关,但调节性cis元素是未知的.
- 拓关联域 (TAD) 是基因组的关键结构单元.
研究的目的:
- 确定调节复制时间和基因组架构的cis元素.
- 研究TAD边界和TAD内部元素在控制这些过程中的作用.
主要方法:
- 在小鼠ESC中进行CRISPR介导的删除和反转.
- 复制时间的分析,A/B区分,TAD架构和转录.
主要成果:
- 对于复制时间,CTCF相关的TAD边界是不必要的.
- 删除CTCF独立的TAD内部接触点 (ERCE) 导致域范围RT转移,A- B区间变化,TAD减弱和转录损失.
- 这些ERCE对于保持基因组结构和功能至关重要.
结论:
- 离散的cis-regulatory元素 (ERCE) 控制整个域的复制时间,分隔,TAD架构和转录.
- 这些发现揭示了基因组结构和功能之间的基本原则.
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