在染色体扫描过程中,CTCF结合元件介导RAG基质的可访问性
Suvi Jain1, Zhaoqing Ba1, Yu Zhang1
1Howard Hughes Medical Institute; Program in Cellular and Molecular Medicine, Boston Children's Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Cell
|May 29, 2018
概括
在抗体V(D) J重组位附近的CTCF结合元件 (CBEs) 提高了V(D) J重组效率. 这发生在意想不到的染色质可访问性功能中,特别是当IGCR1控制区域不活跃时.
科学领域:
- 免疫学
- 分子生物学
- 遗传学
背景情况:
- 抗体重链可变区 (V(D) J) 异构体组合由RAG内核酶在V(D) J重组中心 (RC) 启动.
- IGCR1控制区域通过通过CTCF结合元件 (CBEs) 固定的染色体循环从上游V(H) 段隔离D,J(H和RC元件来促进DJ(H) 的中间形成.
研究的目的:
- 调查V(H) 段对V(H) 到DJ(H) 的重新排列访问DJ(H) RC的机制.
- 阐明CBE在V(H) 部分可访问性和重组潜力的作用.
主要方法:
- 研究了位于V(H) 重组信号序列 (RSS) 下游的CBE的功能.
- 在存在或缺少功能性IGCR1的情况下分析了V(H) 到DJ(H) 的重新排列效率.
- 使用RAG内核酶介导的染色体扫描和循环挤出模型.
主要成果:
- 在V(H) -RSS下游的CBEs显著提高了相关V(H) 段的重组潜力,而不仅仅是RSS功能.
- 这种由CBE介导的增强在IGCR1无活化时特别明显,显示出未预期的增强色素可访问性的功能.
- 在没有IGCR1的情况下,CBEs稳定了在线性RAG扫描中遇到的D-近端V (H) 段之间的相互作用,促进了它们的优先重新排列.
结论:
- 在促进V(H) 段的可访问性和增强V(D) J重组中,CBE发挥着至关重要的作用.
- 这些发现揭示了一种新的机制,即CBE可以促进V{H}访问DJ{H}RC,特别是在IGCR1功能受损的情况下.
- 这突显了CBEs在通过染色体可访问性调节调节抗体基因的意想不到的作用.
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