Cell signaling coordinates global Polycomb Repressive Complex 2 recruitment and developmental gene expression in murine embryonic stem cells (RNA-Seq)

ABSTRACT: In this study, we provide evidence to show that the expression of PRC2-recruting factor Jarid2 is largely reduced in both naïve mESC and Erk1/Erk2 double knockout (Erk1/2-dKO) mESCs, which can be rescued by reactivation of FGF/MARK signaling in naïve mESCs or ectopic Erk1 expression in Erk1/2-dKO mESCs, suggesting the FGF/ERK signaling positively regulates the Jarid2 expression in mESCs. Consistent with the Jarid2 function in the PRC2 recruitment, the global Ezh2 occupancy and histone H3K27me3 are largely reduced at CpG islands (CGIs) and bivalent promoters in both naïve mESCs and Erk1/Erk2-dKO mESCs, which can be fully restored by ectopic expression of Jarid2 expression, suggesting the reduced Jarid2-mediated PRC2 recruitment is a main molecular mechanism leading to the global reduction of PRC2 occupancy at CpG islands and bivalent promoters in naïve mESCs. At the transcriptional level, although both PRC2 occupancy and histone H3K27me3 modification are reduced at bivalent promoters, there exist two groups of genes with distinct expression status. the FGF/ERK signaling target genes are silenced while the Wnt signaling target genes are largely de-repressed, which is caused by the chemical activation of Wnt/beta-catenin signaling in naïve mESCs. Further ChIP-seq analyses demonstrate an increased occupancy of β-catenin at its activated gene promoters in naïve mESCs. These results suggest the transcriptional activation of bivalent genes in naïve mESCs is predominantly determined by the presence of transcriptional factors but not the status of PRC2 occupancy at gene promoters.

ORGANISM(S): Mus musculus

PROVIDER: GSE157747 | GEO | 2020/10/13

REPOSITORIES: GEO