Successful pregnancy relies on dynamic control of cell signaling to achieve uterine receptivity and the necessary biological changes required for endometrial decidualization, embryo implantation, and fetal development. Glucocorticoids are master regulators of intracellular signaling and can directly regulate embryo implantation and endometrial remodeling during murine pregnancy. In immortalized human uterine cells, we have shown that glucocorticoids and estradiol (E2) coregulate thousands of genes. Recently, glucocorticoids and E2 were shown to coregulate the expression of Left-right determination factor 1 (LEFTY1), previously implicated in the regulation of decidualization. To elucidate the molecular mechanism by which glucocorticoids and E2 regulate the expression of LEFTY1, immortalized and primary human endometrial cells were evaluated for gene expression and receptor recruitment to regulatory regions of the LEFTY1 gene. Glucocorticoid administration induced expression of LEFTY1 messenger RNA and protein and recruitment of the glucocorticoid receptor (GR) and activated polymerase 2 to the promoter of LEFTY1. Glucocorticoid-mediated recruitment of GR was dependent on pioneer factors FOXA1 and FOXA2. E2 was found to antagonize glucocorticoid-mediated induction of LEFTY1 by reducing recruitment of GR, FOXA1, FOXA2, and activated polymerase 2 to the LEFTY1 promoter. Gene expression analysis identified several genes whose glucocorticoid-dependent induction required FOXA1 and FOXA2 in endometrial cells. These results suggest a molecular mechanism by which E2 antagonizes GR-dependent induction of specific genes by preventing the recruitment of the pioneer factors FOXA1 and FOXA2 in a physiologically relevant model.
Pubmed ID: 28938408 RIS Download
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This polyclonal targets FOXA1, FOXA2
View all literature mentionsThis monoclonal targets actin
View all literature mentionsThis unknown targets Rabbit Normal igg Control antibody
View all literature mentionsThis monoclonal targets Glucocorticoid Receptor (D8H2) XP Rabbit mAb
View all literature mentionsThis monoclonal targets Ki-67
View all literature mentionsThis polyclonal targets POLR2AphosphoS2
View all literature mentionsThis polyclonal targets Foxa1
View all literature mentionsThis monoclonal targets FOXA2 antibody [EPR4465]
View all literature mentionsThis monoclonal targets Glucocorticoid Receptor (D8H2) XP Rabbit mAb
View all literature mentionsThis polyclonal targets Foxa1
View all literature mentionsThis monoclonal targets FOXA2 antibody [EPR4465]
View all literature mentionsThis polyclonal targets POLR2AphosphoS2
View all literature mentionsThis polyclonal targets FOXA1, FOXA2
View all literature mentionsThis monoclonal targets Ki-67
View all literature mentionsThis monoclonal targets actin
View all literature mentionsThis unknown targets Rabbit Normal igg Control antibody
View all literature mentions