Identification of a Novel Protein Interactions that Elucidates the Mechanism of Hydatidiform Molar Pregnancies in Women with NLRP2 and NLRP7 Mutations

Abstract

Abstract Mutations in NLRP2 and NLRP7 genes result in genetic maternal imprinting disorders. These genes have been identified to be maternal effect genes regulating early embryo development in idiopathic recurrent miscarriage. Previous research suggests that NLRP2 and NLRP7 regulate DNA methylation and immune signaling through inflammasome formation. However, the exact mechanisms underlying recurrent miscarriages are not known. In this study, we report a novel protein interaction of Human proliferation-associated 2G4 (PA2G4, aka: EBP1) with NLRP2 and NLRP7 through an unbiased yeast 2-hybrid screen of a human HeLa cell cDNA library. Protein interactions were confirmed by co-immunoprecipitation and confocal microscopy. Furthermore, global DNA methylation decreased in cells that overexpressed NLRP2/7 and EBP1. Our results further support the role for NLRP2/7 in regulating DNA methylation as a mechanism for recurrent miscarriages. Since EBP1 is implicated in apoptosis, cell proliferation, and differentiation, our discovery significantly advances our understanding of NLR biology and helps to explain the cellular pathways involved in idiopathic recurrent miscarriages. Supported by grants from Beta Beta Beta Biological Honor Society