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多组学分析揭示了雌性哺乳动物单细胞介质热点动态和表观遗传学规则

Jingyi Li¹, Jiansen Lu¹, Jiayu Chen²

¹School of Life Sciences, Biomedical Pioneering Innovative Center, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; New Cornerstone Science Laboratory, Beijing Advanced Innovation Center for Genomics (ICG), Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China.

|July 30, 2025

概括

女性胚胎生殖细胞显示可变的重组热点活动. 诸如H3K4me3和H3K9me3之类的表观遗传标记调节这些热点,从而影响 DNA 变异过程中的双链断裂修复.

科学领域:

遗传学和表观遗传学
生殖生物学生殖生物学
分子生物学分子生物学

背景情况:

对于遗传多样性至关重要的一种微生物重组,是通过在特定热点的DNA双链断裂 (DSBs) 开始的.
由于对胚胎生殖细胞 (EGC) 的访问有限,对女性生殖细胞中这些重组热点的调节知之甚少.

研究的目的:

以单细胞分辨率绘制全基因组范围的活跃重组热点,并量化它们在雌性EGC中的活性.
研究女性EGC中这些热点的表观基因组调节,包括核细胞定位和基因组修饰.

主要方法:

在雌性胚胎生殖细胞中全基因组活跃重组热点的单细胞分辨率映射.
在重组热点上分析核细胞定位和基因组修饰 (H3K4me3,H3K9me3).
表观遗传状态与热点活动频率的相关性.

主要成果:

在个人女性EGC中确定了重组热点使用频率的高变化.
发现PRDM9介导的开放色素和H3K4me3在高频热点上早已建立.
在雌性重组热点周围发现了H3K9me3的丰富,形成了独特的H3K4me3 / H3K9me3双价状态,并建议其在DSB修复中的作用.

结论:

提供了对重组热点及其在雌性EGC中的表观基因组调节的详细地图.
在雌性重组热点中表现出一种新的双价表观遗传状态 (H3K4me3 / H3K9me3).
表明,适当的H3K9me3水平是下游DNA双链断裂修复所必需的.

关键词:

CP: 发育生物学 H3K4me3-H3K9me3 双价性的时间在ULI-NChIP-seqq中使用.胚胎阶段的生殖细胞的低输入MNase-seqq.介质重组热点是介质重组的热点.一个单细胞的ATAC-seqq.

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