Cooperation between NSPc1 and DNA methylation represses HOXA11 expression and promotes apoptosis of trophoblast cells during preeclampsia

Abstract

Accumulating evidence has shown that the apoptosis of trophoblast cells plays an important role in the pathogenesis of preeclampsia, and an intricate interplay between DNA methylation and polycomb group (PcG) protein-mediated gene silencing has been highlighted recently. Here, we provide evidence that the expression of nervous system polycomb 1 (NSPc1), a BMI1 homologous polycomb protein, is significantly elevated in trophoblast cells during preeclampsia, which accelerates trophoblast cell apoptosis. Since NSPc1 acts predominantly as a transcriptional inactivator that specifically represses HOXA11 expression in trophoblast cells during preeclampsia, we further show that NSPc1 is required for DNMT3a recruitment and maintenance of the DNA methylation in the HOXA11 promoter in trophoblast cells during preeclampsia. In addition, we find that the interplay of DNMT3a and NSPc1 represses the expression of HOXA11 and promotes trophoblast cell apoptosis. Taken together, these results indicate that the cooperation between NSPc1 and DNMT3a reduces HOXA11 expression in preeclampsia pathophysiology, which provides novel therapeutic approaches for targeted inhibition of trophoblast cell apoptosis during preeclampsia pathogenesis.

Keywords

• preeclampsia
• nervous system polycomb 1
• DNA methyltransferase 3a
• HOXA11
• apoptosis