Polycomb Repressive Complex 1 (PRC1) Mediated Function Is Critical for Uterine Stromal Cell Decidualization

Presentation Number: SUN-0031
Date of Presentation: June 22nd, 2014

Fenghua Bian*1, Fei Gao1 and Sanjoy K Das2
1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Abstract

Uterine stromal cell decidualization critically depends on the tight control of gene regulation through expression, as well as, repression at the site of implantation. Previously, we showed that Cbx4, a component of the polycomb repressive complex 1 (PRC1), exhibits DNA hypomethylation in the promoter region with the activation of expression during stromal cell decidualization. Epigenetic regulation via polycomb repressive complex 1 (PRC1) plays a major role in genetic repression, although its role during the progression of decidualization remains unknown. To elucidate this notion, we first examined the cell-specific expression of Cbx4 at mRNA and protein levels during decidualization in mice. Our results revealed that Cbx4 is increased primarily in the antimesometrial decidual bed in association with polyploidy. Additionally, other PRC1 members (Cbx2, Cbx6, Cbx7, Cbx8, Ring1A, Ring1B, Mel18, and Bmi1) were also detected during decidual progression. Because PRC1 contributes to DNA compaction for gene repression via monoubiquitination of histone H2A at lysine 119 (ubH2A-K119), and because H3K27me3 is also responsible for the onset of PRC1 function, we further analyzed the expression of these histone marks in conjunction with PRC1 complex regulators by dual immunofluorescence studies. We found that the co-localization of Ring1B/Bmi1 with ubH2AK119 and Cbx4/2 with H3K27me3 was revealed in polyploid cells, suggesting PRC1-dependent function is involved in terminal differentiation with polyploidy development during decidualization. More importantly, we found that the suppression of Cbx4 by siRNA or pharmacological inhibition of Bmi1/Ring1A in the PRC1 complex resulted in a failure of decidualization, development of polyploidy, and inhibition of ubH2AK119 levels. Furthermore, mice harboring Ring1B conditional knockout (Ring1Bfl/fl/PgrCre/+) demonstrated symptoms of sterility with severe decidualization defects in early pregnancy. These results suggest that PRC1-dependent control essentially contributes to the successful progression of decidualization in early pregnancy.

 

Nothing to Disclose: FB, FG, SKD