The histone demethylase KDM5C represses trophoblast proliferation and invasion in woman with recurrent miscarriage [ChIP-seq]

KDM5C is a H3K4- specific demethylase, which has multiple biological roles in development and disease. However, the role of KDM5C in trophoblasts at the maternal-fetal interface remains unknown. Here, we showed that KDM5C was upregulated in placental trophoblasts from patient with recurrent miscarriage (RM). Trophoblasts proliferation and invasion was inhibited by KDM5C overexpression and was enhanced by KDM5C knockdown. Interestingly, KDM5C knockdown promoted trophoblast invasion in villous explant culture system. RNA-seq and ChIP-seq analyses revealed that KDM5C exerts anti-proliferation and anti-invasion effect by directly modulating H3K4 methylation level to repress the expression of a number of key regulatory genes. We show that two of these genes, TGFß2, RAGE, are essential for the proliferation and invasion of trophoblasts. Taken together, our results show that the KDM5C is regulator of trophoblast function during early pregnancy and indicated that KDM5C may be involved in the pathogenesis of RM. To characterize genome-wide H3K4me3 chromatin-state of HTR-8/SVneo cells. Overall design: Examination of H3K4me3 in HTR-8/SVneo cells transduced with control or KDM5C-expression vector