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首页> 外文期刊>Epigenetics & Chromatin >Methylation and hydroxymethylation of CpG display dynamic landscapes in early embryo development and define differentiation into embryonic and placental lineages
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Methylation and hydroxymethylation of CpG display dynamic landscapes in early embryo development and define differentiation into embryonic and placental lineages

机译：CpG的甲基化和羟甲基化在早期胚胎发育中显示动态景观，并定义了分化为胚胎和胎盘谱系

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Covalent modifications to cytosine provide importantepigenetic information required for normal embryodevelopment. 5’methylcytosine (5mC) has received mostexperimental attention while 5’hydroxymethyl cytosine(5hmC) has assumed recent prominence. Extant goldstandardmethods of analysis of do not discriminatebetween 5mC and 5hmC hence most published methylomeshave limits to their interpretation. Immunolocalizationallows discrimination between the range ofmodifications, provides a genome-wide level of analysis,allows differential assessment of nuclear localisation,and is compatible with the limited DNA available withinthe early embryo. Using newly established methodologyfor full retrieval of these two antigens [1] we have reassessedthe patterns of expression of 5mC and 5hmCacross preimplantation development. Both the male andthe female pronuclei show extensive and relatively stablestaining of both 5mC and 5hmC across all stages ofzygotic maturation. The analysis does not provide supportfor the oft claimed active global demethylation ofthe paternally-derived genome relative to that of thematernal-derived genome, and also provide no supportfor a role of 5hmC as an intermediate in such an activedemethylation step. During the cleavage stage of development(2-cell to 8-cell) mC became progressively moreassociated with heterochromatic regions of the nucleuswhile 5hmC staining was the dominant modification ineuchromatin. By the morulae stage several cells with innerpositions in the embryo showed some reduced euchromaticstaining of 5hmC and 5mC. Relative to trophectodermalcells, the pluripotent inner cell mass of blastocysts show amarked overall reduction in euchromatic of both 5hmCand 5mC staining, and a progressive reduction of mC stainingfrom heterochromatic foci. The distinctively differentlandscapes of 5mC and 5hmC on the embryonic genomeindicate that these modifications may provide different epigeneticinformation to the early embryo, and shows thatdifferential changes in this landscape define the first differentiationevents in the early embryo. Current claims ofextensive remodelling of CpG in the zygote seem to belargely caused by dynamic changes in the conformation ofchromatin in early development leading to extensive antigenicmasking of these modifications. When this maskingis removed a much greater level of stability of these modificationsat a global level becomes evident.
机译：对胞嘧啶的共价修饰提供了正常胚胎发育所需的重要表观遗传信息。 5’甲基胞嘧啶（5mC）受到了最多的实验关注，而5’羟甲基胞嘧啶（5hmC）则在近期受到关注。现有的金标准分析方法无法在5mC和5hmC之间进行区分，因此，大多数已发表的甲基化方法对其解释都有限制。免疫定位可以在修饰范围之间进行区分，可以提供全基因组范围的分析水平，可以对核定位进行差异评估，并且可以与早期胚胎中可用的有限DNA兼容。使用新建立的方法来完全检索这两种抗原[1]，我们重新评估了5mC和5hmCacross植入前发育的表达模式。在合子成熟的所有阶段，雄性和雌性前核均显示5mC和5hmC的广泛且相对稳定的染色。该分析不支持父系衍生基因组相对于母本衍生基因组的经常要求的主动全局去甲基化，并且也不提供5hmC作为这种主动去甲基化步骤中的中间体的作用。在发育的裂解阶段（2细胞到8细胞），mC逐渐与细胞核的异色区域更相关，而5hmC染色是主要的修饰异染色质。到桑期，胚胎中有一些内部位置的细胞显示出5hmC和5mC的常染色减少了。相对于滋养层真皮细胞，胚泡的多能内部细胞团在5hmC和5mC染色的常染色体显着降低，并且从异色病灶逐渐降低mC染色。胚胎基因组上5mC和5hmC的明显不同的景观表明这些修饰可能为早期胚胎提供了不同的表观遗传信息，并表明该景观的差异性变化定义了早期胚胎中的第一个分化事件。目前关于合子中CpG广泛重塑的说法似乎主要是由于染色质构象在早期发育中的动态变化导致这些修饰的广泛抗原掩盖而引起的。当去除这种掩膜时，这些修饰的更高水平的稳定性在全球范围内变得显而易见。

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