Maternally expressed NLRP2 links the subcortical maternal complex (SCMC) to fertility, embryogenesis and epigenetic reprogramming.
Mammalian parental genomes contribute differently to early embryonic development. Before activation of the zygotic genome, the maternal genome provides all transcripts and proteins required for the transition from a highly specialized oocyte to a pluripotent embryo. Depletion of these maternally-encoded transcripts frequently results in failure of preimplantation embryonic development, but their functions in this process are incompletely understood. We found that female mice lacking NLRP2 are subfertile because of early embryonic loss and the production of fewer offspring that have a wide array of developmental phenotypes and abnormal DNA methylation at imprinted loci. By demonstrating that NLRP2 is a member of the subcortical maternal complex (SCMC), an essential cytoplasmic complex in oocytes and preimplantation embryos with poorly understood function, we identified imprinted postzygotic DNA methylation maintenance, likely by directing subcellular localization of proteins involved in this process, such as DNMT1, as a new crucial role of the SCMC for mammalian reproduction.
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, 77030, USA.|Century Scholars Program, Rice University, Houston, Texas, 77005, USA.|Shared Equipment Authority, Rice University, Houston, Texas, 77005, USA.
Sangeetha
S
Mahadevan
Department of Molecular Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA.
Varsha
V
Sathappan
Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas, 77030, USA.
Budi
B
Utama
Jan and Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas, 77030, USA.
Isabel
I
Lorenzo
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, 77030, USA.
Khalied
K
Kaskar
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, 77030, USA.|Century Scholars Program, Rice University, Houston, Texas, 77005, USA.|Jan and Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas, 77030, USA.
Ignatia B
IB
Van den Veyver
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001755:Blastocyst / Q000378:metabolism; D048430:Cell Shape; D065150:Cellular Reprogramming / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D005298:Fertility / Q000235:genetics; D005306:Fertilization / Q000235:genetics; D018392:Genomic Imprinting; D008297:Male; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D011256:Pregnancy Outcome; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D046912:Multiprotein Complexes; C572552:Nlrp2 protein, mouse; D011506:Proteins