H1 基因组通过局部染色体紧缩来控制表观遗传
Michael A Willcockson1, Sean E Healton1, Cary N Weiss1
1Department of Cell Biology, Albert Einstein College of Medicine, New York, NY, USA.
Nature
|December 10, 2020
概括
通过压缩染色体来控制基因活性. 在T细胞中消耗H1激活基因,改变表观遗传标记和3D基因组组织,揭示H1
科学领域:
- 分子生物学
- 表观遗传学
- 基因组学
背景情况:
- 链接基因组H1是丰富的染色体蛋白质,对核细胞间距和染色体折叠至关重要.
- 在体内,H1链接蛋白的功能在很大程度上没有被描述.
- 了解H1的作用是解密染色体结构和基因调节的关键.
研究的目的:
- 调查H1链接蛋白在控制染色体凝聚和基因表达中的活体作用.
- 阐明H1影响表观遗传和3D基因组组织的机制.
主要方法:
- 一个条件的三重H1淘汰赛小鼠菌株的生成.
- 在造血细胞,特别是T细胞中减少H1.
- 使用染色体构造捕获 (Hi-C) 的染色体结构分析.
- 基因组甲基化标记 (H3K27,H3K36) 和基因表达的评估.
主要成果:
- 在T细胞中H1枯竭抑制T细胞激活基因,模仿正常激活.
- H1介导的紧缩局限于H1密度高的基因组区域,包括Hi-C B区和PRC2-标记的A区.
- 减少H1静态度改变了表观遗传标记 (减少H3K27me3,增加H3K36me3) 并改变了Hi-C区间.
- 在体外,H1促进PRC2介导的H3K27甲基化,并通过染色体紧缩抑制NSD2介导的H3K36甲基化.
结论:
- 当地H1密度通过基因组紧缩来调节抑制和活性染色体域之间的平衡.
- H1是基因沉默的关键调节者,通过控制染色体紧缩,3D基因组组织和表观遗传.
- 这些发现为H1在建立和维持表观遗传状态中的作用提供了机械的见解.
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