PT - JOURNAL ARTICLE AU - Mohammad B. Aljazi AU - Yuen Gao AU - Yan Wu AU - George I. Mias AU - Jin He TI - Cell signaling coordinates global Polycomb Repressive Complex 2 recruitment and gene expression in murine embryonic stem cells AID - 10.1101/597674 DP - 2020 Jan 01 TA - bioRxiv PG - 597674 4099 - http://biorxiv.org/content/early/2020/01/17/597674.short 4100 - http://biorxiv.org/content/early/2020/01/17/597674.full AB - The recruitment of Polycomb repressive complex 2 (PRC2) to gene promoters is critical for its function in repressing gene expression in murine embryonic stem cells (mESCs). However, previous studies have demonstrated although the expression of early lineage-specific genes is largely repressed, the genome-wide PRC2 occupancy is unexpectedly reduced in naïve mESCs. In this study, we provide evidence to show the FGF/ERK signaling determines the global PRC2 occupancy through regulating the expression of PRC2-recruting factor JARID2 in naïve mESCs. At the transcriptional level, the de-repression of bivalent genes is predominantly determined by the presence of cell signaling-associated transcription factors but not the status of PRC2 occupancy at gene promoters. Hence, this study not only reveals a key molecular mechanism by which the FGF/ERK signaling in regulating the PRC2 occupancy in mESCs, but also elucidates a fundamental question regarding the functional roles of transcription factors and Polycomb-mediated epigenetic mechanisms in transcriptional regulation.