需要TAD-依赖的子TAD进行增强剂-促进剂相互作用,使β-环球蛋白转录成为可能
Dasoul Lee1, Jin Kang1, AeRi Kim1
1Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan, Republic of Korea.
概括
拓关联域 (TAD) 和子TAD对于基因调节至关重要. 破坏TADs会损害子TADs和基因转录,突出显示增强剂-促进剂相互作用的等级关系.
科学领域:
- 基因组学就是基因组学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 拓关联域 (TADs) 是真核生物中基因组组织的基本单元.
- TADs和sub-TADs被边界划分,这些边界被丰富了建筑蛋白CTCF.
- 在调节基因表达方面,TADs和子TADs之间的精确等级关系仍然不完全理解.
研究的目的:
- 研究TADs和子TADs在基因组组织和基因调节中的相互依存关系.
- 确定TAD和亚TAD干扰对基因转录和增强剂-促进剂相互作用的作用.
- 阐明拓领域形成中的等级依赖性.
主要方法:
- 在MEL/ch11细胞中的β-环球蛋白位点的TAD和sub-TAD边界中破坏CTCF结合动机.
- 对基因转录,增强剂-促进剂相互作用和基因素修饰 (H3占用率,H3K27ac) 的分析.
- 在神经前代细胞中CTCF介导的拓域干扰的全基因组分析.
主要成果:
- 一个TAD的破坏会影响其子TAD的形成,而子TAD的破坏不会影响TAD.
- 无论是TAD还是亚TAD的破坏,都导致β-环球蛋白转录的减少和增强剂-促进剂相互作用的丧失.
- 尽管域中断,但H3占用率和H3K27ac等质子修改在很大程度上保持了.
- 在全基因组中,CTCF介导域的破坏减少了神经前体细胞中的增强剂-促进剂相互作用和基因转录.
结论:
- 在TAD和子TAD形成之间存在着分层和不平等的关系,TAD是子TAD的上游.
- 形成依赖于TADs的子TADs对于提供增强剂-促进剂相互作用和基因转录所需的染色质环境至关重要.
- 单独的TAD可能不足以实现强大的基因转录;子TAD在这个过程中发挥着关键作用.
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