NLRP7 affects trophoblast lineage differentiation, binds to overexpressed YY1 and alters cpg methylation

Authors

Sangeetha Mahadevan, Baylor College of Medicine
Shu Wen, Baylor College of Medicine
Ying Wooi Wan, Baylor College of Medicine
Hsiu Huei Peng, Baylor College of Medicine
Subhendu Otta, Baylor College of Medicine
Zhandong Liu, Baylor College of Medicine
Michelina Iacovino, University of Minnesota Twin Cities
Elisabeth M. Mahen, University of Minnesota Twin Cities
Michael Kyba, University of Minnesota Twin Cities
Bekim Sadikovic, Baylor College of MedicineFollow
Ignatia B. Van den Veyver, Baylor College of Medicine

Document Type

Article

Publication Date

2-1-2014

Journal

Human Molecular Genetics

Volume

23

Issue

3

First Page

706

Last Page

716

URL with Digital Object Identifier

10.1093/hmg/ddt457

Abstract

Maternal-effect mutations in NLRP7 cause rare biparentally inherited hydatidiform moles (BiHMs), abnormal pregnancies containing hypertrophic vesicular trophoblast but no embryo. BiHM trophoblasts display abnormal DNA methylation patterns affecting maternally methylated germline differentially methylated regions (gDMRs), suggesting that NLRP7 plays an important role in reprogramming imprinted gDMRs. How NLRP7-a component of the CATERPILLAR family of proteins involved in innate immunity and apoptosis-causes these specific DNA methylation and trophoblast defects is unknown. Because rodents lack NLRP7, we used human embryonic stem cells to study its function and demonstrate that NLRP7 interacts with YY1, an important chromatin-binding factor. Reduced NLRP7 levels alter DNA methylation and accelerate trophoblast lineage differentiation. NLRP7 thus appears to function in chromatin reprogramming and DNA methylation in the germline or early embryonic development, functions not previously associated with members of the NLRP family. © The Author 2013. Published by Oxford University Press. All rights reserved.