Date of Graduation

Summer 2022

Degree

Master of Science in Biology

Department

Biology

Committee Chair

Christopher Lupfer

Abstract

The protein NOD-Like receptor pyrin domain containing 2 (NLRP2) is one member of a larger family of protein receptors that plays an important role in our innate immune system. In humans, the NLR family consists of 22 proteins. However, only about a half of NLRs’ functions are known, but many are pro-inflammatory, causing inflammation. NLRP2 has been identified to be a maternal effect gene regulating early embryo development in idiopathic recurrent miscarriages. In previous studies, mutations in the NLRP2 gene resulted in genetic maternal imprinting disorders due to NLRP2 regulating DNA methylation. However, the exact mechanisms involved in recurrent miscarriages are unknown. In this study, I report a novel protein interaction of Human proliferation-associated 2G4 (PA2G4, aka; EBP1) with NLRP2 through an unbiased yeast 2-hybrid screen of a human HeLa cell cDNA library. Protein interactions were confirmed by co-immunoprecipitation, confocal microscopy, and FRET analysis. Furthermore, global DNA methylation decreased in cells that overexpressed NLRP2 and EBP1. These results further support the role of NLRP2 in regulating DNA methylation as a mechanism for recurrent miscarriages. Since EBP1 is implicated in apoptosis, cell proliferation, and differentiation, my discovery significantly advances our understanding of NLR biology and helps to explain the cellular pathways involved in idiopathic recurrent miscarriages.

Keywords

NOD-like receptors, idiopathic recurrent miscarriage, hydatidiform molar pregnancies, miscarriage, EBP1, DNA methylation

Subject Categories

Biology | Cell and Developmental Biology | Genetics and Genomics | Immunology and Infectious Disease

Copyright

© Nayeon Son

Available for download on Monday, May 01, 2023

Open Access

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