Chromatin Landscape Instructs Precise Transcription Factor Regulome during Embryonic Lineage Specification [RNA-seq]

Embryos originate from fertilized eggs and are shaped through continuous cell division and differentiation, accompanied by dramatic changes in transcription, translation, and metabolism. Epigenetic information and transcription factors (TFs) play indispensable roles in regulating these processes. Recently, the trophoblast regulator TFAP2C was found to be essential in initiating the earliest cell fate decisions. However, Tfap2c transcripts are still detectable in both the inner cell mass (ICM) and trophectoderm (TE) of blastocysts, raising questions regarding how TFAP2C functions once these two lineages are established. In this study, we delineated the dynamics of TFAP2C during the mouse peri-implantation stage and elucidated its collaboration with the key lineage regulators CDX2 and NANOG. Importantly, we proposed that de novo formation of H3K9me3 in the extraembryonic ectoderm during implantation antagonizes TFAP2C binding to crucial developmental genes, thereby maintaining its lineage identity. Together, this research highlights the plasticity of the epigenetic environment in designating the genomic binding of highly adaptable lineage-specific TFs and regulating embryonic cell fates.