文献阅读 | Resetting histone modifications during human parental-to-zygotic transition

Resetting histone modifications during human parental-to-zygotic transition

人类亲本-合子转变中组蛋白修饰重编程

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MARINa (MAster Regulator INference algorithm)

MARINa
MARINA (Master Regulator Inference Algorithm) MAster Regulator INference algorithm (MARINa), designed to infer transcription factors (TFs) controlling the transition between the two phenotypes, A and B, and the maintenance of the latter phenotype. Expression at the mRNA level is often a poor predictor of a TF's regulatory activity and an even worst predictor of its biological relevance in regulating phenotype-specific programs. To obviate this problem, MARINa infers TF activity from the global transcriptional activation of its regulon (i.e. its activated and repressed targets) and its biological relevance by TF-regulon overlap with phenotype-specific programs.

获悉胚胎基因组激活前“基因组重启”后，团队进一步关注胚胎ZGA后转录调控通路，采用MARINa算法寻找了发育阶段特异性的转录激活因子，令人惊喜的是“分化转录通路图谱”正确预测了已知的胚胎细胞向EPI, PE 和TE分化相关转录调控因子，并鉴定了新的潜在转录因子可能调控细胞分化;团队进一步研究通过D5、D6和D7囊胚的TE与ICM发现ICM和TE不对称的表观遗传类型。研究团队结合染色质图谱和已发表的单细胞转录数据，预测了人类各谱系的关键调控因子。并发现在人囊胚的内细胞团和滋养外胚层中，许多内细胞团（包括上胚层和原始内胚层）的特异基因会被H3K27me3所标记，而滋养外胚层的特异基因则几乎没有这样的标记，揭示不同谱系基因在早期发育分化过程中具有差异性表观遗传调控，这种标记模式可能和不同谱系命运决定的差异相关。

参考：

《Science》：郑大一附院孙莹璞/徐家伟课题组、清华大学颉伟课题组合作研究揭示人类早期胚胎发育“表观基因组重启”机制