Landscape of TFs binding in mouse early embryos [CUT&RUN-seq]

In mammals, early lineage specification originates from the establishment of cell polarization in early embryos, before providing the foundation for all somatic development. Although there have been heated debates about whether transcription factors (TFs) or epigenetic information plays the dominant role in cell fate decisions, the precise annotation of TFs remains largely elusive in early embryos, restricting the functional study of developmentally important TFs. Here, we investigated the genome-wide landscapes of two known triggers of mouse embryo polarization: transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4). We found that Tfap2c can bridge the connection between the promoter and the proximal enhancer, and further facilitate the functions of downstream Tead4 and Klf5 in boosting polarization. Our study also implicated that Rarg-initiated active demethylation might be a prerequisite for proper Tfap2c functioning. Furthermore, the results demonstrated that both genomic imprinting and nucleotide polymorphism can instruct TF binding, leading to allele-specific expression in early embryos. Overall, our study characterized TF dynamics during the peri-implantation stage and revealed their spatiotemporal interactions with the epigenetic environment in driving polarization and lineage specification.