针对CTCF的降解使染色体域的局部隔离脱离基因组分离
Elphège P Nora1, Anton Goloborodko2, Anne-Laure Valton3
1Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, USA.
Cell
|May 20, 2017
概括
转录因子CTCF对于哺乳动物的染色体折叠和拓关联域 (TAD) 的组织至关重要. 在CTCF
科学领域:
- 基因组学
- 分子生物学
- 表观遗传学
背景情况:
- 哺乳动物染色体折叠的机制尚未完全理解.
- 转录因子CTCF参与调节染色体结构.
研究的目的:
- 研究CTCF在哺乳动物染色体折叠和拓关联域 (TAD) 的组织中的作用.
- 确定CTCF是否对维持基因组分离和其作为转录绝缘体的功能至关重要.
主要方法:
- 在小鼠胚胎干细胞中利用了辅酶诱导的降解系统.
- 耗尽CTCF以观察对染色体折叠,TAD绝缘和基因组分离的影响.
- 恢复CTCF水平以评估其在染色体组织中的指导作用.
主要成果:
- 在CTCF目标部位和TAD隔离之间以剂量依赖的方式循环使用CTCF是必不可少的.
- 恢复CTCF可以重新建立适当的染色体结构,证明其指导功能.
- CTCF耗尽不会破坏活跃和非活跃基因组组的分离.
- CTCF通过增强剂阻断进行转录隔离,而不是通过防止异色素的传播.
结论:
- 在哺乳动物染色体折叠和TAD组织中发挥关键作用.
- 基因组分离独立于CTCF介导的TAD隔离.
- 通过增强剂阻断,CTCF作为转录绝缘体,而不是阻断异色素的扩散.
- 这些发现提供了对哺乳动物基因组组织的基本见解.
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