Oxytocin receptor is regulated by Peg3

Frey, Wesley D.; Sharma, Kaustubh; Cain, Terri L; Nishimori, Katsuhiko; Teruyama, Ryoichi; Kim, Joomyeong

doi:10.1371/journal.pone.0202476

Cited by 8 publications

(8 citation statements)

References 21 publications

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“…The Peg3 dosages also affected the expression levels of Acly in embryos (Figs 3 , 4A and 4B ). These results comply with the previous studies showing the DNA-binding capability of PEG3 and controlling the expression levels of several downstream genes, including Oxtr , H19 , Msl1 , and Msl3 [ 34 , 44 , 46 , 47 ]. In the mammary gland, Peg3 dosage appeared to be associated with the expression level of the key gene, Acly , connecting the glucose metabolism and lipid synthesis ( Fig 6 ).…”

Section: Discussionsupporting

confidence: 93%

PEG3 controls lipogenesis through ACLY

Ghimire

Kim

2021

PLoS ONE

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Peg3 (Paternally expressed gene 3) is an imprinted gene encoding a DNA-binding protein that is a well-known transcriptional repressor. Previous studies have shown that the mutant phenotypes of Peg3 are associated with the over-expression of genes involved in lipid metabolism. In the current study, we investigated four potential downstream genes of Peg3, which were identified through ChIP-seq data: Acly, Fasn, Idh1, and Hmgcr. In vivo binding of PEG3 to the promoter region of these key genes involved in lipogenesis was subsequently confirmed through individual ChIP experiments. We observed the opposite response of Acly expression levels against the variable gene dosages of Peg3, involving 0x, 1x, and 2x Peg3. This suggests the transcriptional repressor role of Peg3 in the expression levels of Acly. Another set of analyses showed a sex-biased response in the expression levels of Acly, Fasn, and Idh1 against 0x Peg3 with higher levels in female and lower levels in male mammary glands. These results overall highlight that Peg3 may be involved in regulating the expression levels of several key genes in adipogenesis.

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Section: Discussionsupporting

confidence: 93%

PEG3 controls lipogenesis through ACLY

Ghimire

Kim

2021

PLoS ONE

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“…However, another study found no lactation deficiencies (Denizot et al, 2016), possibly due differences in the position of the deletion, the genetic background of the mouse models used, or the methodologies applied. Interestingly, a more recent study shows that oxytocin receptor is regulated by Peg3 (Frey et al, 2018), suggesting that Peg3 can influence milk production as a secondary effect by influencing expression of the oxytocin receptor. Igf2, another imprinted gene expressed from the paternal allele, mediates prolactin-induced morphogenesis in the mammary gland (Brisken et al, 2002), and has been shown to be produced specifically by hormone-receptor positive cells in early pregnancy (De Silva, Kunasegaran, Ghosh, & Pietersen, 2015).…”

Section: Evidence For Imprinting In the Mammary Glandmentioning

confidence: 99%

The evolution of genomic imprinting: Epigenetic control of mammary gland development and postnatal resource control

Hanin

Ferguson‐Smith

2019

WIREs Mechanisms of Disease

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Genomic imprinting is an epigenetically regulated process leading to gene expression according to its parental origin. Imprinting is essential for prenatal growth and development, regulating nutritional resources to offspring, and contributing to a favored theory about the evolution of imprinting being due to a conflict between maternal and paternal genomes for the control of prenatal resources—the so‐called kinship hypothesis. Genomic imprinting has been mainly studied during embryonic and placental development; however, maternal nutrient provisioning is not restricted to the prenatal period. In this context, the mammary gland acts at the maternal‐offspring interface providing milk to the newborn. Maternal care including lactation supports the offspring, delivering nutrients and bioactive molecules protecting against infections and contributing to healthy organ development and immune maturation. The normal developmental cycle of the mammary gland—pregnancy, lactation, involution—is vital for this process, raising the question of whether genomic imprinting might also play a role in postnatal nutrient transfer by controlling mammary gland development. Characterizing the function and epigenetic regulation of imprinted genes in the mammary gland cycle may therefore provide novel insights into the evolution of imprinting since the offspring's paternal genome is absent from the mammary gland, in addition to increasing our knowledge of postnatal nutrition and its relation to life‐long health. This article is categorized under: Developmental Biology > Developmental Processes in Health and Disease

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“…As is known, Peg3 is widely expressed in various tissues of humans and mice, encodes a DNA-binding protein involved in the control of speci c target genes of different cell functions [46] and plays a role as a transcriptional regulator for the expression of OTR. In Peg3-KO mice, the expression of OTR in hypothalamus and breast were up-regulated [35]. In this study, we rst proved that M2 supernatant and TGF-β promoted the expression of OT by suppressing the expression of peg3 in enteric neurons.…”

Section: Discussionmentioning

confidence: 70%

“…Peg3 (Paternally Expressed Gene 3) encodes a DNA binding protein that acts as a inhibitory transcriptional regulator for the expression of OTR [35]. So, we hypothesized that cytokines released from polarized macrophage might in uence OT signaling system expression through Peg3.…”

Section: Peg3 Was Involved In the Upregulation Of Ot And Otr Expression Induced By M2 Macrophages Polarizationmentioning

confidence: 99%

The effect of macrophages polarization on the expression of oxytocin signaling system in enteric neurons

Shi

Zhang

et al. 2021

Preprint

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Background: The aim of the current study is to investigate the effect of macrophages polarization on the expression of oxytocin (OT) and oxytocin receptor (OTR) in enteric neurons. Methods: In this study, we used a classic colitis model to observe the correlation between macrophages polarization and OT signaling system. In order to further demonstrate the effect of macrophages, we examined the expression of OT signaling system after depletion of macrophages. Results: The data showed that, in vitro, flowing macrophages polarization to M1 type by LPS, the macrophages supernatant inhibited the expression of OT and OTR in cultured enteric neurons through releasing pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α); flowing macrophages polarization to M2 type by IL4, the macrophages supernatant promoted the expression of OT and OTR in cultured enteric neurons through releasing anti-inflammatory cytokine (TGF-β). Furthermore, M1 macrophages decreased the expression of OT signaling system mainly through STAT3/NF-κB pathways in cultured enteric neurons; M2 macrophages increased expression of OT signaling system mainly through activation of Smad2/3 and inhibiting the expression of Peg3 in cultured enteric neurons. In DSS model, we demonstrated that macrophages were polarized to M1 type during the inflammatory phases, the expression of OT and OTR decreased significantly; and macrophages were polarized to M2 type during the recovery phases, the expression of OT and OTR increased significantly. At the same time, we also found that D-mannose increased the expression of OT and OTR through polarization of macrophages to M2 type. Conclusions: This is the first time to prove that the polarization of macrophages differentially regulates the expression of OT and OTR in enteric neurons.

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Oxytocin receptor is regulated by Peg3

Cited by 8 publications

References 21 publications

PEG3 controls lipogenesis through ACLY

PEG3 controls lipogenesis through ACLY

The evolution of genomic imprinting: Epigenetic control of mammary gland development and postnatal resource control

The effect of macrophages polarization on the expression of oxytocin signaling system in enteric neurons

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