Abstract
Imprinted genes play important roles in placental and embryonic development. Neuronatin (NNAT), first identified as an imprinted gene in human and mouse brains, played important roles in neuronal differentiation in the brain and in glucose-mediated insulin secretion in pancreatic β cells. In the pig, NNAT was reported to be imprinted in eleven tissues. Our previous microarray hybridization study showed that NNAT was differentially expressed in Yorkshire and Meishan pig placentas, but the imprinting status and function of NNAT in the placenta have not been investigated. We demonstrated for the first time that NNAT was monoallelically expressed in the placenta. Immunochemistry analysis showed that NNAT was located in the uterine luminal and glandular epithelium in placentas. We also confirmed the differential expression of NNAT in Meishan and Yorkshire pig placentas by qPCR. Using IPA software and the published literature, we created a model network of the possible relationships between NNAT and glucose transporter genes. A dual luciferase reporter assay demonstrated that the crucial promoter region of NNAT contained a CANNTG sequence in the +210 to +215 positions, which corresponded to the E-box. Our findings demonstrated important roles of NNAT in placenta function.
Highlights
Imprinted genes are a special category of genes that imprinted one allele in the early embryo development decided by the parental origin
Two transcripts of NNAT existed in porcine placenta, and both of them were expressed in the placentas of Yorkshire and Meishan pigs at different developmental stages (Fig. 2)
NNAT was an important gene in regulating mouse brain and adipocyte differentiation and insulin secretion in response to glucose in mouse pancreatic cells [7,8,9]
Summary
Imprinted genes are a special category of genes that imprinted one allele in the early embryo development decided by the parental origin. The theory raised by Morre and Haig [1] was widely demonstrated that imprinting evolved in mammals because of the conflicting interests of maternal and paternal genes in transferring of nutrients from the mother to her offspring. Maternally imprinted genes Mest and Grb play important roles in the placental and fetal development of mammals. Further study showed that the weight of Yorkshire placentas dramatically increased from day of gestation to term, while in Meishan pigs, the weight of the fetus, not the placenta, increased during this period [5]. These studies indicated that Meishan and Yorkshire pig placentas have different nutrient transport capacities
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