The fate and function of epigenetic marks during the germline-to-embryo transition is a key issue in developmental biology, with relevance to stem cell programming and transgenerational inheritance. In zebrafish, DNA methylation patterns are programmed in transcriptionally quiescent cleavage embryos; paternally inherited patterns are maintained, whereas maternal patterns are reprogrammed to match the paternal. Here, we provide the mechanism by demonstrating that "Placeholder" nucleosomes, containing histone H2A variant H2A.Z(FV) and H3K4me1, virtually occupy all regions lacking DNA methylation in both sperm and cleavage embryos and reside at promoters encoding housekeeping and early embryonic transcription factors. Upon genome-wide transcriptional onset, genes with Placeholder become either active (H3K4me3) or silent (H3K4me3/K27me3). Notably, perturbations causing Placeholder loss confer DNA methylation accumulation, whereas acquisition/expansion of Placeholder confers DNA hypomethylation and improper gene activation. Thus, during transcriptionally quiescent gametic and embryonic stages, an H2A.Z(FV)/H3K4me1-containing Placeholder nucleosome deters DNA methylation, poising parental genes for either gene-specific activation or facultative repression.

中文翻译：

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占位符核小体是胚芽到胚DNA甲基化重编程的基础。

种系到胚胎过渡过程中表观遗传标记的命运和功能是发育生物学中的关键问题，与干细胞编程和跨代遗传有关。在斑马鱼中，DNA甲基化模式是在转录静止的卵裂胚胎中编程的。保留了父本继承的模式，而对母本模式进行了重新编程以匹配父本。在这里，我们通过证明包含组蛋白H2A变体H2A.Z（FV）和H3K4me1的“占位符”核小体来提供机制，实际上占据了精子和卵裂胚中都缺乏DNA甲基化的所有区域，并位于编码管家和早期胚胎转录的启动子上因素。在全基因组转录开始后，带有占位符的基因变为活跃的（H3K4me3）或沉默的（H3K4me3 / K27me3）。值得注意的是，引起占位符丢失的扰动会导致DNA甲基化积累，而占位符的获取/扩展会赋予DNA低甲基化和不适当的基因激活。因此，在转录静止的配子和胚胎阶段，含有H2A.Z（FV）/ H3K4me1的占位符核小体可以阻止DNA甲基化，为基因特异性激活或兼性阻遏做好准备。