Widespread Enhancer Dememorization and Promoter Priming during Parental-to-Zygotic Transition

The epigenome plays critical roles in controlling gene expression and development. However, how the parental epigenomes transit to the zygotic epigenome in early development remains elusive. Here we show that parental-to-zygotic transition in zebrafish involves extensive erasure of parental epigenetic memory, starting with methylating gametic enhancers. Surprisingly, this occurs even prior to fertilization for sperm. Both parental enhancers lose histone marks by the 4-cell stage, and zygotic enhancers are not activated until around zygotic genome activation (ZGA). By contrast, many promoters remain hypomethylated and, unexpectedly, acquire histone acetylation before ZGA at as early as the 4-cell stage. They then resolve into either activated or repressed promoters upon ZGA. Maternal depletion of histone acetyltransferases results in aberrant ZGA and early embryonic lethality. Finally, such reprogramming is largely driven by maternal factors, with zygotic products mainly contributing to embryonic enhancer activation. These data reveal widespread enhancer dememorization and promoter priming during parental-to-zygotic transition. [Display omitted] •Extensive erasing and rewriting of histone marks in zebrafish early development•Enhancers undergo dememorization during parental-to-zygotic transition•Sperm (but not oocyte) enhancers are pre-methylated prior to fertilization•Widespread promoter priming occurs prior to ZGA How the parental epigenomes transit to the zygotic epigenome is a crucial question in developmental biology. By exploring the reprogramming of histone modifications from gametes to post-ZGA embryos in zebrafish, Zhang et al. unveiled widespread enhancer dememorization and promoter priming during parental-to-zygotic transition, which may be conserved in vertebrate development.