在TAD边界的普遍RNA结合蛋白丰富调节了TAD组织
Qiang Sun1,2, Qin Zhou1,2, Yulong Qiao1,2
1Department of Orthopaedics and Traumatology, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong SAR, China.
Nucleic acids research
|January 8, 2025
概括
RNA结合蛋白 (RBPs) 是新发现的基因组架构的调节者. 这项研究揭示了RBP与拓关联域 (TAD) 边界结合,影响TAD绝缘强度和组织,特别是通过共同转录过程.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 哺乳动物基因组组织依赖于CTCF和凝聚力,用于拓关联域 (TAD).
- 控制TAD形成和维护的精确机制尚未完全理解.
- 在3D基因组组织中RNA结合蛋白 (RBPs) 的作用在很大程度上仍未被探索.
研究的目的:
- 调查RBPs在TADs组织中的潜在作用.
- 识别与TAD边界相关联的RBP并描述它们的功能.
主要方法:
- 全球RBP结合和3D基因组映射数据 (K562和HepG2细胞) 的综合分析.
- 在RBP丰富,TAD绝缘和转录活性之间的相关性分析.
- 实验验证使用RBFox2淘汰和差异化模型 (C2C12神经细胞).
- 对转录抑制对RBP结合和TAD绝缘的影响的评估.
主要成果:
- RBPs经常在TAD边界上得到丰富,定义了与边界相关的RBPs (baRBPs).
- baRBP结合与TAD绝缘强度的增加相关,独立于CTCF.
- baRBP结合与新生的促进体转录有关.
- RBFox2倒置导致轻微的TAD重组;其丰富性在肌肉细胞分化过程中保持和动态调节.
- 转录抑制破坏了baRBP结合和TAD边界绝缘.
结论:
- RBPs积极调节TAD组织.
- 同转录协会和与新生转录的相互作用是RBP介导的TAD调节的关键机制.
- RBPs代表了一种影响基因组架构的新型因素.
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