基因组组织和DNA可访问性控制试管体中的抗原变异
Laura S M Müller1,2,3, Raúl O Cosentino1,2,3, Konrad U Förstner4,5,6
1Department of Veterinary Sciences, Experimental Parasitology, Ludwig-Maximilians-Universität München, Munich, Germany.
Nature
|October 19, 2018
概括
病原体使用抗原变异来逃避宿主免疫力. 这项研究将基因组变异与基因组结构联系起来,影响Trypanosoma brucei中的抗原基因表达和免疫逃避.
科学领域:
- 遗传学
- 分子生物学
- 寄生虫学
背景情况:
- 致病生物使用抗原变异来逃避宿主免疫反应.
- 抗原变异依赖于大型,多样化的抗原基因储存和调节的表达.
- 三维基因组架构和DNA可访问性影响同源重组和基因表达.
研究的目的:
- 确定连接三维基因组结构,染色体构造和抗原变异的因素.
- 克服像Trypanosoma brucei这样的病原体中的反复抗原基因阵列的挑战.
主要方法:
- 使用长读序列的抗原基因阵列的新型单元组合.
- 全基因组染色体构成捕获 (Hi-C) 来分析基因组分离.
- 在现场光杂交,ATAC-seq和单细胞RNA测序以评估染色体和基因表达.
- 研究基因组变异H3.V和H4.V的作用.
主要成果:
- 在Trypanosoma brucei中,抗原编码子端粒区域被组织成不同的紧区.
- 删除H3.V和H4.V基因突变促进了抗原-基因聚类,并增加了DNA的可访问性.
- 通过同源重组增强抗原表达切换.
结论:
- 基因组变异H3.V和H4.V作为基因组架构,染色质构造和抗原变异之间的分子链接.
- 这一发现为病原体免疫逃避策略的调节提供了新的见解.
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