RT Journal Article
SR Electronic
T1 FGF/MAPK signaling pathway regulates the genome-wide occupancy of Polycomb Repressive Complex 2 in murine embryonic stem cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 597674
DO 10.1101/597674
A1 Aljazi, Mohammad B.
A1 Gao, Yuen
A1 Wu, Yan
A1 Mias, George I.
A1 He, Jin
YR 2019
UL http://biorxiv.org/content/early/2019/04/03/597674.abstract
AB Previous studies demonstrated that genome-wide PRC2 occupancy is largely reduced in primitive mESCs cultured in 2 inhibitors-containing medium. To understand the underlying mechanisms, we performed RNA-sequencing analyses to show the expression of Jarid2 and Eed is significantly reduced in primitive mESCs due to blocking of the FGF/MAPK pathway. ChIP-seq analyses showed that decreased genome-wide occupancy of Ezh2 and H3K27me3 modification is correlated with a global reduction of Jarid2 occupancy. The ectopic expression of Jarid2 partially restores both global PRC2 occupancy and H3K27me3 modification. Further gene expression analyses showed the reduced global PRC2 occupancy does not lead to de-repression of lineage differentiation genes in primitive mESCs. Together, these results revealed the FGF/MAPK signaling pathway is critical in determining the global PRC2 occupancy through regulating the expression of PRC2 components. The reduced Jarid2-mediated PRC2 recruitment is the main molecular mechanism leading to the global reduction of PRC2 occupancy in primitive mESCs.