宝子们，今天要和大家分享一项超厉害的科研发现！生命的繁衍离不开精子的健康发育，而背后其实隐藏着精密的表观遗传调控机制。表观遗传编程就像是细胞命运的“指挥官”，通过巧妙地控制基因的激活和抑制，决定着细胞的发展方向。其中H3K4me3一直被认为是基因激活的“小旗帜”，但在精子持续发育的系统里，它到底怎么调控转录输出和时间，之前一直不太清楚。研究人员深入探索，详细描绘了雄性生殖细胞的表观基因组图谱。哇塞，他们发现了数千个精子细胞特有的广泛H3K4me3结构域，这可是之前都没被好好研究过的呢！这些结构域和H3K27ac标记的增强子、启动子重叠，就像一群默契的小伙伴，共同协调基因转录，精确控制基因表达的时间。而且哦，这些广泛的H3K4me3还会和常规的H3K4me3竞争转录机器，保证关键基因能在合适的时间、以合适的强度表达。要是这个机制被破坏，精子发育可就会出问题啦。另外，在细胞分裂的关键时期，异染色质标记的分布也会发生显著变化，和基因沉默紧密相关。这项研究让我们看到了精子发生过程中高度协调的表观遗传调控，也揭示了Setd1b的新作用。宝子们，是不是感觉生命的奥秘真的很神奇🧐！科研的每一次突破都让我们离真相更近一步，期待未来有更多关于生命繁衍的秘密被揭开。

期刊

Cell Research

标题

SETD1B-mediated broad H3K4me3 controls proper temporal patterns of gene expression critical for spermatid development

作者

Zhen Lin, Bowen Rong, Ruitu Lyu, Yuxuan Zheng, Yao Chen, Junyi Yan, Meixia Wu, Xiaogang Gao, Fuchou Tang, Fei Lan & Ming-Han Tong

摘要

Epigenetic programming governs cell fate determination during development through intricately controlling sequential gene activation and repression. Although H3K4me3 is widely recognized as a hallmark of gene activation, its role in modulating transcription output and timing within a continuously developing system remains poorly understood. In this study, we provide a detailed characterization of the epigenomic landscapes in developing male germ cells. We identified thousands of spermatid-specific broad H3K4me3 domains regulated by the SETD1B-RFX2 axis, representing a previously underappreciated form of H3K4me3. These domains, overlapping with H3K27ac-marked enhancers and promoters, play critical roles in orchestrating robust transcription and accurate temporal control of gene expression. Mechanistically, these broad H3K4me3 compete effectively with regular H3K4me3 for transcriptional machinery, thereby ensuring robust levels and precise timing of master gene expression in mouse spermiogenesis. Disruption of this mechanism compromises the accuracy of transcription dosage and timing, ultimately impairing spermiogenesis. Additionally, we unveil remarkable changes in the distribution of heterochromatin marks, including H3K27me3 and H3K9me2, during the mitosis-to-meiosis transition and completion of meiotic recombination, which closely correlates with gene silencing. This work underscores the highly orchestrated epigenetic regulation in spermatogenesis, highlighting the previously unrecognized role of Setd1b in the formation of broad H3K4me3 domains and transcriptional control, and provides an invaluable resource for future studies toward the elucidation of spermatogenesis.

原文链接

https://www.nature.com/articles/s41422-025-01080-0

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静远嘲风（MY Scimage） 成立于2007年，嘲风取自中国传统文化中龙生九子，子子不同的传说，嘲风为守护屋脊之瑞兽，喜登高望远；静远取自成语“宁静致远”，登高莫忘初心，远观而不可务远。

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