MAT2A is essential for zygotic genome activation by maintaining of histone methylation in porcine embryos

IF 2.4 2区农林科学 Q3 REPRODUCTIVE BIOLOGY

Theriogenology Pub Date : 2024-09-10 DOI:10.1016/j.theriogenology.2024.09.006

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引用次数: 0

Abstract

Methionine adenosyltransferase 2A (MAT2A) is an essential enzyme in the methionine cycle that generates S-adenosylmethionine (SAM) by reacting with methionine and ATP. SAM acts as a methyl donors for histone and DNA methylation, which plays key roles in zygotic genome activation (ZGA). However, the effects of MAT2A on porcine ZGA remain unclear. To investigate the function of MAT2A and its underlying mechanism in porcine ZGA, MAT2A was knocked down by double-stranded RNA injection at the 1-cell stage. MAT2A is highly expressed at every stage of porcine embryo development. The percentages of four-cell-stage embryos and blastocysts were lower in the MAT2A-knockdown (KD) group than in the control group. Notably, depletion of MAT2A decreased the levels of H3K4me2, H3K9me2/3, and H3K27me3 at the four-cell stage, whereas MAT2A KD reduced the transcriptional activity of ZGA genes. MAT2A KD decreased embryonic ectoderm development (EED) and enhancer of zeste homolog 2 (EZH2) expression. Exogenous SAM supplementation rescued histone methylation levels and developmental arrest induced by MAT2A KD. Additionally, MAT2A KD significantly increased DNA damage and apoptosis. In conclusion, MAT2A is involved in regulating transcriptional activity and is essential for regulating histone methylation during porcine ZGA.

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MAT2A 在猪胚胎中通过维持组蛋白甲基化对子代基因组激活至关重要

蛋氨酸腺苷基转移酶 2A（MAT2A）是蛋氨酸循环中的一种重要酶，它通过与蛋氨酸和 ATP 反应生成 S-腺苷蛋氨酸（SAM）。SAM 是组蛋白和 DNA 甲基化的甲基供体，在子代基因组激活（ZGA）中发挥着关键作用。然而，MAT2A 对猪 ZGA 的影响仍不清楚。为了研究 MAT2A 在猪 ZGA 中的功能及其内在机制，我们在猪 1 细胞阶段通过注射双链 RNA 敲除了 MAT2A。MAT2A 在猪胚胎发育的每个阶段都有高表达。与对照组相比，MAT2A 基因敲除（KD）组中四细胞期胚胎和囊胚的百分比较低。值得注意的是，MAT2A的消耗降低了四细胞期H3K4me2、H3K9me2/3和H3K27me3的水平，而MAT2A KD降低了ZGA基因的转录活性。MAT2A KD降低了胚胎外胚层发育（EED）和泽斯特同源增强子2（EZH2）的表达。补充外源 SAM 可挽救组蛋白甲基化水平和 MAT2A KD 诱导的发育停滞。此外，MAT2A KD 会显著增加 DNA 损伤和细胞凋亡。总之，MAT2A参与了转录活性的调节，并且在猪ZGA过程中对组蛋白甲基化的调节至关重要。

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

Theriogenology 农林科学-生殖生物学

CiteScore

5.50

自引率

14.30%

发文量

387

审稿时长

72 days

期刊介绍： Theriogenology provides an international forum for researchers, clinicians, and industry professionals in animal reproductive biology. This acclaimed journal publishes articles on a wide range of topics in reproductive and developmental biology, of domestic mammal, avian, and aquatic species as well as wild species which are the object of veterinary care in research or conservation programs.