Coordination of zygotic genome activation entry and exit by H3K4me3 and H3K27me3 in porcine early embryos.
Coordination of zygotic genome activation entry and exit by H3K4me3 and H3K27me3 in porcine early embryos.
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猪早期胚胎中 H3K4me3 和 H3K27me3 协调合子基因组激活进入和退出
DOI：
10.1101/gr.276207.121
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发表时间：
2022-08-25
期刊：
影响因子：
7
通讯作者：
Miao, Yi-Liang
中科院分区：
文献类型：
--
作者：
Bu, Guowei;Zhu, Wei;Liu, Xin;Zhang, Jingjing;Yu, Longtao;Zhou, Kai;Wang, Shangke;Li, Zhekun;Fan, Zhengang;Wang, Tingting;Hu, Taotao;Hu, Ruifeng;Liu, Zhiting;Wang, Tao;Wu, Linhui;Zhang, Xia;Zhao, Shuhong;Miao, Yi-Liang
组蛋白修饰是与基因表达相关的染色质状态的关键表观遗传指标。虽然H3 K4 me 3和H3 K27 me 3的重编程模式已在小鼠和人类植入前胚胎中阐明，但这些标记与合子基因组激活（ZGA）之间的关系仍然知之甚少。通过超低输入天然染色质免疫沉淀和测序，我们分析了猪卵母细胞和体外受精（IVF）胚胎中的全局H3 K4 me 3和H3 K27 me 3。我们在卵母细胞中观察到ZGA基因启动子的尖锐H3 K4 me 3峰，这些峰在受精后变得更宽，并在ZGA期间再次重塑为尖锐峰。通过同时耗竭H3 K4 me 3去甲基化酶KDM 5 B和KDM 5C，我们确定广泛的H3 K4 me 3结构域维持损害ZGA基因表达，表明其功能是防止过早进入ZGA。与此相反，广泛的H3 K27 me 3结构域进行全面删除受精后，随后重新建立H3 K4 me 3/H3 K27 me 3二价桑椹胚。我们还发现，双价标记沉积在ZGA基因的启动子，抑制这种沉积与ZGA基因的激活。这表明启动子的二价性有助于ZGA在猪胚胎中的退出。此外，我们证明了H3 K4 me 3和H3 K27 me 3的异常重编程在体细胞核移植（SCNT）胚胎中触发ZGA失调，而H3 K27 me 3介导的印迹在猪IVF和SCNT胚胎中不存在。我们的研究结果突出了两个以前未知的表观遗传重编程模式与ZGA协调猪植入前胚胎。最后，在猪和人组蛋白修饰动力学之间观察到的相似性表明，猪胚胎也可能是人类胚胎研究的有用模型。
Histone modifications are critical epigenetic indicators of chromatin state associated with gene expression. Although the reprogramming patterns of H3K4me3 and H3K27me3 have been elucidated in mouse and human preimplantation embryos, the relationship between these marks and zygotic genome activation (ZGA) remains poorly understood. By ultra-low-input native chromatin immunoprecipitation and sequencing, we profiled global H3K4me3 and H3K27me3 in porcine oocytes and in vitro fertilized (IVF) embryos. We observed sharp H3K4me3 peaks in promoters of ZGA genes in oocytes, and these peaks became broader after fertilization and reshaped into sharp peaks again during ZGA. By simultaneous depletion of H3K4me3 demethylase KDM5B and KDM5C, we determined that broad H3K4me3 domain maintenance impaired ZGA gene expression, suggesting its function to prevent premature ZGA entry. In contrast, broad H3K27me3 domains underwent global removal upon fertilization, followed by a re-establishment for H3K4me3/H3K27me3 bivalency in morulae. We also found that bivalent marks were deposited at promoters of ZGA genes, and inhibiting this deposition was correlated with the activation of ZGA genes. It suggests that promoter bivalency contributes to ZGA exit in porcine embryos. Moreover, we demonstrated that aberrant reprogramming of H3K4me3 and H3K27me3 triggered ZGA dysregulation in somatic cell nuclear transfer (SCNT) embryos, whereas H3K27me3-mediated imprinting did not exist in porcine IVF and SCNT embryos. Our findings highlight two previously unknown epigenetic reprogramming modes coordinated with ZGA in porcine preimplantation embryos. Finally, the similarities observed between porcine and human histone modification dynamics suggest that the porcine embryo may also be a useful model for human embryo research.
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5.9
作者：
Liu X;Chen L;Wang T;Zhou J;Li Z;Bu G;Zhang J;Yin S;Wu D;Dou C;Xu T;He H;Zhu W;Yu L;Liu Z;Zhang X;Chen ZX;Miao YL
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通讯作者：
Salzberg, Steven L.
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5.9
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4.4
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Cao S;Han J;Wu J;Li Q;Liu S;Zhang W;Pei Y;Ruan X;Liu Z;Wang X;Lim B;Li N
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Li N
影响因子：
16.6
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Santini L;Halbritter F;Titz-Teixeira F;Suzuki T;Asami M;Ma X;Ramesmayer J;Lackner A;Warr N;Pauler F;Hippenmeyer S;Laue E;Farlik M;Bock C;Beyer A;Perry ACF;Leeb M
通讯作者：
Leeb M