Mapping putative enhancers in mouse oocyte and early embryo reveals TCF3/12 as key folliculogenesis regulators

Dynamic epigenomic reprogramming occurs during mammalian oocyte maturation and early development. However, the underlying transcription circuitry remains poorly characterized. By mapping cis-regulatory elements using H3K27ac, we identified putative enhancers in mouse oocytes and early embryos distinct from those in adult tissues, enabling global transitions of regulatory landscapes around fertilization and implantation. Gene deserts harbor prevalent putative enhancers in fully-grown oocytes linked to oocyte-specific gene and repeat activation. Embryo-specific enhancers are primed prior to zygotic genome activation and are restricted by oocyte-inherited H3K27me3. Putative enhancers in oocytes often manifest H3K4me3, bidirectional transcription, Pol II binding, and can drive transcription in STARR-seq and a reporter assay. Finally, motif analysis of these elements identified crucial regulators of oogenesis – TCF3 and TCF12, the deficiency of which impairs activation of key oocyte genes and folliculogenesis. These data reveal distinctive regulatory landscapes and their interacting TFs that underpin the development of mammalian oocytes and early embryos. STAR ChIP-seq, ATAC-seq , RNA-seq, STARR-seq, and DamID were applied on mouse oocytes, pre-implantation embryos, and cell lines.