循环挤出介于RAG扫描的生理性IGH位置收缩
Hai-Qiang Dai1,2, Hongli Hu3,4, Jiangman Lou3,4
1Howard Hughes Medical Institute, Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA. hai-qiang.dai@childrens.harvard.edu.
Nature
|January 14, 2021
概括
在原始B细胞中研究RAG扫描显示,位点收缩独立于V(D) J重组. 这一过程由凝聚素介导的循环挤出和CTCF结合元件调节,影响DNA的可访问性.
科学领域:
- 免疫学
- 分子生物学
- 遗传学
背景情况:
- RAG内核酶通过扫描染色体以检测重组信号序列 (RSS) 来启动Igh V(D) J重组.
- 凝聚素介导的循环挤出促进了远程RAG扫描,而CTCF结合元件 (CBE) 可能会阻碍这一过程.
- 在原始B细胞中,V(H) 位经历了鲜为人知的收缩,这可能会改善远端V(H) 的可访问性.
研究的目的:
- 阐明V(H) 位置收缩背后的机制及其对RAG扫描的影响.
- 研究循环挤出和CBEs在原生B细胞中调节V(D) J重组中的作用.
主要方法:
- 在小鼠原始原生B细胞中分析V(H) 位点逆转.
- 评估V(H) -RSS和神秘的RSS重排.
- 评估RAG扫描超出V (H) 的位置.
- 研究翅膀分离样蛋白同类物 (WAPL) 的表达和耗尽.
主要成果:
- 尽管局部收缩,但V ((H) 位逆转取消了V ((H) -RSS和通常收的加密RSS重排.
- 逆转激活了对立方向的加密VH-RSS和RAG扫描超出VH位置.
- 初级 B 细胞的低 WAPL 表达与局部收缩和 RAG 扫描相关; WAPL 枯竭激活了这些过程.
结论:
- 通过循环挤出在原始B细胞中,CBE阻碍的放松促进RAG扫描V(H) 位点.
- 循环挤出涉及V(H) 位置收缩,WAPL影响凝聚力学.
- 这些发现提供了对V (H) 位点可访问性和V (D) J重组调节的机制性见解.
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