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 parental-to-zygotic transition in zebrafish involves extensive erasure of parental epigenetic memory starting by 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 de novo histone acetylation as early as at 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 contributing to embryonic enhancer activation. Thus, these data revealed widespread enhancer dememorization and promoter priming during parental-to-zygotic transition.