Li Xiao-Han, Lee Song-Hee, Lu Qin-Yue, Zhan Cheng-Lin, Lee Gyu-Hyun, Kim Ji-Dam, Sim Jae-Min, Song Hyeon-Ji, Cui Xiang-Shun
Department of Animal Science, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea.
Department of Animal Science, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea.
Theriogenology. 2024 Dec;230:81-90. doi: 10.1016/j.theriogenology.2024.09.006. Epub 2024 Sep 10.
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.
甲硫氨酸腺苷转移酶2A（MAT2A）是甲硫氨酸循环中的一种关键酶，它通过与甲硫氨酸和ATP反应生成S-腺苷甲硫氨酸（SAM）。SAM作为组蛋白和DNA甲基化的甲基供体，在合子基因组激活（ZGA）中起关键作用。然而，MAT2A对猪ZGA的影响尚不清楚。为了研究MAT2A在猪ZGA中的功能及其潜在机制，在单细胞阶段通过注射双链RNA敲低MAT2A。MAT2A在猪胚胎发育的各个阶段均高表达。MAT2A敲低（KD）组的四细胞期胚胎和囊胚的百分比低于对照组。值得注意的是，MAT2A的缺失降低了四细胞期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zeste同源物2增强子（EZH2）的表达。外源性SAM补充可挽救MAT2A KD诱导的组蛋白甲基化水平和发育停滞。此外，MAT2A KD显著增加了DNA损伤和细胞凋亡。总之，MAT2A参与调节转录活性，并且在猪ZGA过程中对调节组蛋白甲基化至关重要。
