Human Reproduction UnitKolling Institute Sydney Medical, School University of Sydney, Sydney, Australia.
Human Reproduction UnitKolling Institute Sydney Medical, School University of Sydney, Sydney, Australia
Reproduction. 2017 Oct;154(4):375-385. doi: 10.1530/REP-17-0112.
Acetylation of histone proteins is a major determinant of chromatin structure and function. Fertilisation triggers a round of chromatin remodelling that prepares the genome for the first round of transcription from the new embryonic genome. In this study we confirm that fertilisation leads to a marked progressive increase in the level of histone 3 lysine 9 acetylation in both the paternally and maternally derived genomes. The culture of zygotes in simple defined media caused a marked increase in the global level of acetylation and this affected the male pronucleus more than the female. The culture created a marked asymmetry in staining between the two pronuclei that was not readily detected in zygotes collected directly from the reproductive tract and was ameliorated to some extent by optimized culture media. The increased acetylation caused by culture resulted in increased transcription of , a marker of embryonic genome activation. Pharmacological analyses showed the hyperacetylation of H3K9 and the increased expression of caused by culture were due to the altered net activity of a range of histone acetylases and deacetylases. The marked hyperacetylation of histone 3 lysine 9 caused by culture of zygotes may serve as an early biomarker for the effects of culture on the normal function of the embryo. The results also provide further evidence for an effect of the stresses associated with assisted reproductive technologies on the normal patterns of epigenetic reprogramming in the early embryo.
组蛋白的乙酰化是染色质结构和功能的主要决定因素。受精引发一轮染色质重塑，为新胚胎基因组的第一轮转录做准备。在这项研究中，我们证实受精导致父源和母源基因组中组蛋白 3 赖氨酸 9 乙酰化水平明显渐进性增加。胚胎在简单定义的培养基中培养会导致整体乙酰化水平显著增加，这种影响对雄性原核比雌性原核更为明显。培养在两个原核之间造成了明显的不对称性染色，而在直接从生殖道收集的胚胎中则不易检测到，通过优化培养基在一定程度上得到了改善。培养引起的乙酰化增加导致 转录增加，这是胚胎基因组激活的一个标志。药理学分析表明，培养引起的 H3K9 高度乙酰化和 的表达增加是由于一系列组蛋白乙酰转移酶和去乙酰化酶的净活性改变所致。胚胎培养导致的组蛋白 3 赖氨酸 9 高度乙酰化可能作为培养对胚胎正常功能影响的早期生物标志物。研究结果还进一步证明了与辅助生殖技术相关的应激对早期胚胎中正常表观遗传重编程模式的影响。
