GSE116713
Maternal Eed knockout causes loss of H3K27me3 imprinting and random X-inactivation  in the extra-embryonic cells
Genomic imprinting is essential for mammalian development. Recent studies have revealed that maternal histone H3 lysine 27 tri-methylation (H3K27me3) can mediate DNA methylation-independent genomic imprinting. However, the regulatory mechanisms and functions of this new imprinting mechanism are largely unknown. Here we demonstrate that maternal Eed, an essential component of the Polycomb group complex 2 (PRC2), is required for establishing H3K27me3 imprinting. We found that all H3K27me3 imprinted genes, including Xist, lose their imprinted expression in Eed maternal KO (matKO) embryos, resulting in male-biased lethality. Surprisingly, although maternal X chromosome inactivation (XmCI) occurs in Eed matKO embryos at preimplantation due to loss of Xist imprinting, it is resolved at peri-implantation. Ultimately, both X chromosomes are reactivated in the embryonic cell lineage prior to random XCI, and only a single X chromosome undergoes random XCI in the extra-embryonic cell lineage. Thus, our study not only demonstrates an essential role of Eed in H3K27me3 imprinting establishment but also reveals a unique XCI dynamics in the absence of Xist imprinting. Overall design: mRNA profiling was performed for morula embryos and E6.5 extra-embryonic ectoderm (ExE) of Eed control and maternal knockouts. For morula embryos, two replicates were generated for each group.  For E6.5 ExE samples, four replicates were produced for the control group (2 males and 2 females) and nine replicates were generated for the maternal KO group (5 males and 4 females). H3K27me3 profiling for Eed CTR and matKO morula embryos were performed using CUT&RUN.