Multi-omics analysis reveals single-cell meiotic hotspot dynamics and epigenomic regulations in female mammals.

IF 6.9 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-07-29 DOI:10.1016/j.celrep.2025.116082

Jingyi Li, Jiansen Lu, Jiayu Chen, Qianzheng Fu, Zhenhuan Jiang, Shaorong Gao, Fuchou Tang

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Abstract

Meiotic recombination initiates via DNA double-strand breaks (DSBs) at specialized hotspots, while the regulation of meiotic recombination hotspots in females remain elusive due to the scarcity of embryonic stage germ cells (EGCs). Here, we mapped genome-wide active recombination hotspots and estimated their activities in female EGCs at single-cell resolution, revealing the high variability in hotspot usage frequency among individual germ cells. Further investigation of nucleosome positioning and histone modifications at recombination hotspots revealed that PRDM9-mediated open chromatin and flanking H3K4me3 established earlier at high-frequency hotspots compared with less frequently used ones. Unexpectedly, although recombination hotspots usually distributed outside of heterochromatin, H3K9me3 was clearly enriched around hotspots in females, forming a unique H3K4me3/H3K9me3 bivalent state. And we showed that an appropriate H3K9me3 level may be required for downstream DSB repairs. Together, our results provided understanding about the landscape and epigenomic regulation of recombination hotspots in females.

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多组学分析揭示了雌性哺乳动物单细胞减数分裂热点动态和表观基因组调控。

减数分裂重组通过DNA双链断裂（DSBs）在特定的热点启动，而由于胚胎期生殖细胞（EGCs）的稀缺性，女性减数分裂重组热点的调控仍然难以捉摸。在这里，我们绘制了全基因组的活性重组热点，并在单细胞分辨率下估计了它们在女性EGCs中的活性，揭示了单个生殖细胞中热点使用频率的高度变异性。对重组热点核小体定位和组蛋白修饰的进一步研究表明，与较少使用的热点相比，prdm9介导的开放染色质和侧翼H3K4me3在高频热点建立得更早。出乎意料的是，虽然重组热点通常分布在异染色质之外，但H3K9me3在女性的热点周围明显富集，形成了独特的H3K4me3/H3K9me3二价状态。我们发现，下游DSB修复可能需要适当的H3K9me3水平。总之，我们的研究结果提供了对重组热点的景观和表观基因组调控的理解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.