ZGA-Timer: a framework for the identification of key zygotic genome activation genes from time-series RNA-seq data

Zygotic genome activation (ZGA) is a complex process which denotes the initiation of gene expression after fertilization. Deciphering the proper timing and genes involved in ZGA program is still a fundamental challenge in early embryo development. Here, we present a new ZGA gene identification framework, named ZGA-Timer, based on the timecourse pattern from RNA-seq data. By performing ZGA-Timer and siRNA technology, we confirmed Uqcc3 as a novel ZGA gene in mice. As a unique feature of ZGA-Timer, time-series RNA-seq data are modeled by a pattern recognition method and the onset of ZGA can be estimated in multiple species. ZGA-Timer outperforms current foldchange-based approaches. Furthermore, we investigate the epigenetic modifications and find that accessible chromatin predominately contributes to the regulation of ZGA genes. Moreover, ZGA genes show significant enrichment in housekeeping genes and cancer driver genes. Together, our ZGA-Timer framework provides a new approach to further understand the ZGA process. We performed siRNA experiments to verify the potential role of Uqcc3 in embryonic development. We injected siRNAs targeting Uqcc3 into fertilized oocytes at 8 hpi, and performed RNA-seq to siRNA-mediated Uqcc3-depleted embryos and normal embryos as control.