Dynamic landscape of enhancer-derived RNA during mouse early embryo development

Enhancer RNAs (eRNAs) play critical roles in diverse biological processes by mediating the activation of their target genes. However, the systematic landscape and potential regulations and functions of eRNAs during mammalian early embryo development remains elusive. Here, we present the comprehensive detection and characterization of eRNAs during mouse early embryo development. We demonstrated the spatiotemporal and allelic landscape of eRNA expression. We found the asymmetric activation of paternal-specific eRNAs during zygotic genome activation (ZGA). We identified TFs and their cooperation in regulating dynamic eRNA expression. eRNA are involved in multiple developmental signaling pathways through putatively regulating their target genes. Interestingly, we observed that the transcriptions of enhancers themselves are also widely modulated by eRNAs during mouse early embryo development. Critically, we de novo identified a novel eRNA transcribed from a super-enhancer region exclusively expressed at 2-cell stage of mouse early embryos and experimentally validated its key functional role in regulating ZGA and early embryo development. Examination of gene expression in control and SPENH0335 knocked-down mouse embryos of 2-cell stage.