CTCF介导的人类3D基因组架构揭示了转录的染色质拓
Zhonghui Tang1, Oscar Junhong Luo1, Xingwang Li2
1The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06030, USA.
Cell
|December 22, 2015
概括
这项研究揭示了CCCTC结合因子 (CTCF) 和RNA聚合酶II (RNAPII) 如何组织DNA,影响基因活性. 哈普洛型变异影响了这种结构,为基因表达和疾病易感性提供了洞察力.
科学领域:
- 基因组学
- 分子生物学
- 表观遗传学
背景情况:
- 空间基因组组织对于基因调控至关重要.
- 了解染色体折叠和关键蛋白质介导的相互作用是必不可少的.
研究的目的:
- 通过CTCF和RNAPII介导的高阶染色体折叠和染色体相互作用的映射.
- 在基因组组织和基因表达中研究类型变异的作用.
- 提供有关疾病易感性的机制性见解.
主要方法:
- 通过核酸分辨率对结尾标签测序 (ChIA-PET) 进行染色体相互作用分析.
- 在不同的人类细胞系中进行 Haplotype 特定的分析.
- 通过3D基因组模拟.
主要成果:
- CTCF/凝聚蛋白组织构成基因,与RNAPII相互作用以调节细胞类型特异性基因.
- 哈普洛型变异对染色体配置和基因表达有不同的影响.
- CTCF在定义结构调节的部分方面发挥了作用.
结论:
- CTCF和RNAPII调解影响转录的空间基因组组织.
- 代基相互作用和变异会影响基因组结构和基因表达,从而导致疾病.
- 3D基因组策略提供了对人类变异和疾病的洞察力.
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