Skip to main content
ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #307941
Title: NLRP7 affects trophoblast lineage differentiation, binds to overexpressed YY1 and alters CpG methylation

Author
item MAHADEVAN, SANGEETHA - Baylor College Of Medicine
item WEN, SHU - Baylor College Of Medicine
item WAN, YING-WOOI - Baylor College Of Medicine
item PENG, HSIU-HUEI - Baylor College Of Medicine
item OTTA, SUBHENDU - Baylor College Of Medicine
item LIU, ZHANDONG - Baylor College Of Medicine
item IACOVINO, MICHELINA - University Of Minnesota
item MAHEN, ELISABETH - University Of Minnesota
item KYBA, MICHAEL - University Of Minnesota
item SADIKOVIC, BEKIM - Baylor College Of Medicine
item VAN DEN VEYVER, IGNATIA - Children'S Nutrition Research Center (CNRC)

Submitted to: Human Molecular Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/13/2013
Publication Date: 4/1/2014
Citation: Mahadevan, S., Wen, S., Wan, Y., Peng, H., Otta, S., Liu, Z., Iacovino, M., Mahen, E.M., Kyba, M., Sadikovic, B., Van Den Veyver, I.B. 2014. NLRP7 affects trophoblast lineage differentiation, binds to overexpressed YY1 and alters CpG methylation. Human Molecular Genetics. 23(3):706-716.

Interpretive Summary: Biparental Hydatidiform Mole (BiHM) is a rare pregnancy complication in which the placenta becomes abnormally developed and filled with fluid, but cannot sustain growth and development of a fetus. The disease can be caused by a loss of the function of one of two genes, NLRP7 and KHDC3L in pregnant women, which results in abnormal DNA methylation in the placenta. Methylation is a change of DNA that helps regulate turning on and off of genes at the right time and tissue. It is already known that DNA methylation is important in normal function of the placenta, which is the main organ supplying the fetus with nutrients. As part of our larger project to understand the role of NLRP7 and KHDC3L in normal function of the placenta, in this study we tried to better understand the mechanisms by which losing function of these genes causes the abnormal placentas; we found for the first time that losing NLRP7 directly changes where DNA is methylated. While this study does not investigate nutrition-related functions of the placenta itself, it is a component of our work on understanding how genes in placenta are regulated by DNA methylation. This is indirectly important for understanding how the placenta controls fetal nutrition.

Technical 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.