标题：Distinct dynamics of parental 5-hydroxymethylcytosine during human preimplantation development regulate early lineage gene expression
中文标题：在人类植入前发育过程中，亲本5-羟甲基胞嘧啶的不同动态调节早期谱系基因的表达
引用信息：Liang D, Yan R, Long X, Ji D, Song B, Wang M, Zhang F, Cheng X, Sun F, Zhu R, Hou X, Wang T, Zou W, Zhang Y, Pu Z, Zhang J, Zhang Z, Liu Y, Hu Y, He X, Cao Y, Guo F. Distinct dynamics of parental 5-hydroxymethylcytosine during human preimplantation development regulate early lineage gene expression. Nat Cell Biol. 2024 Sep;26(9):1458-1469. doi: 10.1038/s41556-024-01475-y. Epub 2024 Jul 30. PMID: 39080410; PMCID: PMC11392820.
摘要：The conversion of DNA 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by TET enzymes represents a significant epigenetic modification, yet its role in early human embryos remains largely unknown. Here we showed that the early human embryo inherited a significant amount of 5hmCs from an oocyte, which unexpectedly underwent de novo hydroxymethylation during its growth. Furthermore, the generation of 5hmC in the paternal genome after fertilization roughly followed the maternal pattern, which was linked to DNA methylation dynamics and regions of sustained methylation. The 5hmCs persisted until the eight-cell stage and exhibited high enrichment at OTX2 binding sites, whereas knockdown of OTX2 in human embryos compromised the expression of early lineage genes. Specifically, the depletion of 5hmC affected the activation of embryonic genes, which was further evaluated by ectopically expressing mouse Tet3 in human early embryos. These findings revealed distinct dynamics of 5hmC and unravelled its multifaceted functions in early human embryonic development.
中文摘要：通过 TET 酶将 DNA 5-甲基胞嘧啶(5mC)转化为5-羟甲基胞嘧啶(5hmC)代表了一个重要的表观遗传修饰，然而它在早期人类胚胎中的作用在很大程度上仍然是未知的。我们发现早期人类胚胎从卵母细胞中遗传了大量的5hmCs，这些细胞在生长过程中意外地经历了从头羟甲基化。此外，受精后父本基因组中5hmC 的产生大致遵循母本模式，这与 DNA 甲基化动态和持续甲基化区域有关。5hmCs 持续到八细胞阶段，在 OTX2结合位点表现出高度富集，而敲低人类胚胎中的 OTX2损害了早期谱系基因的表达。具体来说，5hmC 的消耗影响胚胎基因的活化，这是通过在人类早期胚胎中异位表达小鼠 Tet3进一步评估的。这些发现揭示了5hmC 的独特动力学，揭示了其在早期人类胚胎发育中的多方面功能。
原文链接：
https://www.nature.com/articles/s41556-024-01475-y
