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

Sangeetha Mahadevan, Shu Wen, Ying Wooi Wan, Hsiu Huei Peng, Subhendu Otta, Zhandong Liu, Michelina Iacovino, Elisabeth M. Mahen, Michael Kyba, Bekim Sadikovic, Ignatia B. Van den Veyver

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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.

Original languageEnglish (US)
Article numberddt457
Pages (from-to)706-716
Number of pages11
JournalHuman molecular genetics
Volume23
Issue number3
DOIs
StatePublished - Feb 2014

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