Pax5 的 Wapl 抑制通过 Igh 循环挤出促进了 V 基因重组
Louisa Hill1, Anja Ebert1, Markus Jaritz1
1Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
Nature
|July 3, 2020
概括
Pax5抑制了亲B细胞中的Wapl,使免疫球蛋白基因重组的染色体循环挤出成为可能. 这一过程重塑了基因组结构,以确保免疫的抗体多样性.
科学领域:
- 基因组学
- 分子生物学
- 表观遗传学
背景情况:
- 染色体组织,包括拓相关的域 (TAD),对于像V(D) J重组这样的核过程至关重要.
- TAD是由染色体循环挤出形成的,这个过程依赖于凝聚素复合体,并由Wapl等因素调节.
- 免疫球蛋白重链 (Igh) 部位需要收缩以进行V(D) J重组,这一过程由亲B细胞中的Pax5控制.
研究的目的:
- 阐明Pax5控制亲B细胞中Igh位点收缩的机制.
- 研究Wapl在Pax5介导的IGH位点收缩中的作用及其对基因组结构的影响.
主要方法:
- 通过Igh位点进行了染色质环挤出研究.
- 在pro-B和pre-B细胞中分析了Pax5对Wapl表达的调节.
- 检查了多抑制复合体2对Wapl促进者的招募.
主要成果:
- 通过循环挤出整个部位来驱动Igh部位的收缩.
- 通过招募多抑制复合体2来抑制pro- B和pre- B细胞中的Wapl表达.
- 发现减少Wapl表达增强了凝聚性存在时间,促进了延长循环挤出,并改变了全球染色体结构.
结论:
- 通过Pax5对Wapl进行抑制对于在Igh位点进行广泛的循环挤出至关重要.
- 基因组结构的结构变化对于使所有V基因重组成为可能,确保抗体多样性至关重要.
- 这项研究揭示了一种新的机制,将转录因子调节与免疫系统发育的大规模染色体组织联系起来.
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