PEG3 is a paternally expressed gene. The 9-kb Peg3 gene transcript that encodes an unusual zinc finger
protein of 1,572 amino acids. The protein has 11 widely spaced C2H2-like zinc finger motifs and 2 groups of amino acid
repeats of approximately 7 to 10 residues with no known function.
NCBI Summary:
In human, ZIM2 and PEG3 are treated as two distinct genes though they share multiple 5' exons and a common promoter and both genes are paternally expressed (PMID:15203203). Alternative splicing events connect their shared 5' exons either with the remaining 4 exons unique to ZIM2, or with the remaining 2 exons unique to PEG3. In contrast, in other mammals ZIM2 does not undergo imprinting and, in mouse, cow, and likely other mammals as well, the ZIM2 and PEG3 genes do not share exons. Human PEG3 protein belongs to the Kruppel C2H2-type zinc finger protein family. PEG3 may play a role in cell proliferation and p53-mediated apoptosis. PEG3 has also shown tumor suppressor activity and tumorigenesis in glioma and ovarian cells. Alternative splicing of this PEG3 gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Sep 2009]
General function
Comment
Cellular localization
Nuclear
Comment
Ovarian function
Comment
PEG3 binds to H19-ICR as a transcriptional repressor. Ye A et al. (2016) Paternally expressed gene 3 (Peg3) encodes a DNA-binding protein with twelve C2H2 zinc finger motifs. In the current study, we performed ChIP-seq using mouse embryonic fibroblast (MEF) cells. This experiment identified a set of 16 PEG3 genomic targets, the majority of which overlapped with the promoter regions of genes with oocyte expression. These potential downstream genes were upregulated in MEF cells lacking PEG3 protein, suggesting a potential repressor role for PEG3. Our study also identified the imprinting control region (ICR) of H19 as a genomic target. According to the results, PEG3 binds to a specific sequence motif located between the 3(rd) and 4(th) CTCF binding sites of the H19-ICR. PEG3 also binds to the active maternal allele of the H19-ICR. The expression levels of H19 were upregulated in MEF cells lacking PEG3, and this upregulation was mainly derived from the maternal allele. This suggests that PEG3 may function as a transcriptional repressor for the maternal allele of H19. Overall, the current study uncovers a potential functional relationship between Peg3 and H19, and also confirms PEG3 as a transcriptional repressor for the identified downstream genes.//////////////////
Expression regulated by
glucose
Comment
High-glucose concentrations change DNA methylation levels in human IVM oocytes. Wang Q et al. (2018) What are the effects of high-glucose concentrations on DNA methylation of human oocytes? High-glucose concentrations altered DNA methylation levels of Peg3 and Adiponectin in human in vitro maturation oocytes. Maternal diabetes has a detrimental influence on oocyte quality including epigenetic modifications, as shown in non-human mammalian species. Immature metaphase I (MI) stage oocytes of good quality were retrieved from patients who had normal ovarian potential and who underwent ICSI in the Reproductive Medicine Center of People's Hospital of Zhengzhou University. MI oocytes were cultured in medium with different glucose concentrations (control, 10 mM and 15 mM) in vitro and 48 h later, oocytes with first polar body extrusion were collected to check the DNA methylation levels. MI oocytes underwent in vitro maturation (IVM) at 37°C with 5% mixed gas for 48 h. Then the mature oocytes were treated with bisulfite buffer. Target sequences were amplified using nested or half-nested PCR and the DNA methylation status was tested using combined bisulfite restriction analysis (COBRA) and bisulfite sequencing (BS). High-glucose concentrations significantly decreased the first polar body extrusion rate. Compared to controls, the DNA methylation levels of Peg3 in human IVM oocytes were significantly higher in 10 mM (P < 0.001) and 15 mM (P < 0.001) concentrations of glucose. But the DNA methylation level of H19 was not affected by high-glucose concentrations in human IVM oocytes. We also found that there was a decrease in DNA methylation levels in the promoter of adiponectin in human IVM oocytes between controls and oocytes exposed to 10 mM glucose (P = 0.028). N/A. It is not clear whether the alterations are beneficial or not for the embryo development and offspring health. The effects of high-glucose concentrations on the whole process of oocyte maturation are still not elucidated. Another issue is that the number of oocytes used in this study was limited. This is the first time that the effects of high-glucose concentration on DNA methylation of human oocytes have been elucidated. Our result indicates that in humans, the high risk of chronic diseases in offspring from diabetic mothers may originate from abnormal DNA modifications in oocytes. This work was supported by the fund of National Natural Science Foundation of China (81401198) and Doctor Foundation of Qingdao Agricultural University (1116008).The authors declare that there are no potential conflicts of interest relevant to this article.//////////////////
Ovarian localization
Oocyte
Comment
Obata Y, et al 2002 reported the maternal primary imprinting is established at a specific time
for each gene throughout oocyte growth.
Primary imprinting during gametogenesis governs the monoallelic
expression/repression of imprinted genes in embryogenesis. Previously, it was
showed that maternal primary imprinting is disrupted in neonate-derived
non-growing oocytes. Here, to investigate precisely when and in what order
maternal primary imprinting progresses, the authors produced parthenogenetic embryos
containing one genome from a non-growing or growth-stage oocyte from 1- to
20-day-old mice and one from a fully grown oocyte of adult mice. They used these
embryos to analyze the expression of eight imprinted genes: Peg1/Mest, Peg3,
Snrpn, Znf127, Ndn, Impact, Igf2r, and p57(KIP2). The results showed that the
imprinting signals for each gene were not all imposed together at a specific
time during oocyte growth but rather occurred throughout the period from
primary to antral follicle stage oocytes. The developmental ability of the
constructed parthenogenetic embryos was gradually reduced as the nuclear donor
oocytes grew. These studies provide the first insight into the process of
primary imprinting during oocyte growth.
Follicle stages
Comment
Molecular cloning, mRNA expression and imprinting status of PEG3, NAP1L5 and PPP1R9A genes in pig. Zhang FW et al. Imprinted genes are expressed monoallelically depending on their parental origin, and play important roles in the regulation of fetal growth, development, and postnatal behavior. Most genes known to be imprinted have been identified and studied in the human and the mouse. However, there are only a small number of reported imprinted genes in pigs. Therefore, identification and characterization of more imprinted genes in pigs is useful for comparative analysis of genomic imprinting across species. In this study, we cloned the porcine PEG3, NAP1L5 and PPP1R9A genes. The imprinting status of these genes was determined using sequencing directly and single nucleotide polymorphisms (SNPs) identified in individuals from reciprocal cross of Meishan and Large White pigs. Imprinting analysis was carried out in 13 different tissues (skeletal muscle, fat, pituitary gland, heart, lung, liver, kidney, spleen, stomach, small intestine, uterus, ovary and testis) from twelve 2-month-old piglets. Imprinting analysis showed that PEG3 and NAP1L5 were exclusively expressed from the paternal allele whereas PPP1R9A was biallelically expressed in all tissues tested where the genes were expressed. The study is of interest to understand the conservation of genomic imprinting among mammals at the 3 loci.
Phenotypes
Mutations
2 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: subfertile Comment: Peg3 mutational effects on reproduction and placenta-specific gene families. Kim J 2014 et al.
Peg3 (paternally expressed gene 3) is an imprinted gene encoding a DNA-binding protein. This gene plays important roles in controlling fetal growth rates and nurturing behaviors. In the current study, a new mutant mouse model has been generated to further characterize the functions of this DNA-binding protein. Besides known phenotypes, this new mutant model also revealed potential roles of Peg3 in mammalian reproduction. Female heterozygotes produce a much smaller number of mature oocytes than the wild-type littermates, resulting in reduced litter sizes. According to genome-wide expression analyses, several placenta-specific gene families are de-repressed in the brain of Peg3 heterozygous embryos, including prolactin, cathepsin and carcinoembryonic antigen cell adhesion molecule (Ceacam) families. The observed de-repression is more pronounced in females than in males. The de-repression of several members of these gene families is observed even in the adult brain, suggesting potential defects in epigenetic setting of the placenta-specific gene families in the Peg3 mutants. Overall, these results indicate that Peg3 likely controls the transcription of several placenta-specific gene families, and further suggest that this predicted transcriptional control by Peg3 might be mediated through unknown epigenetic mechanisms.
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Species: mouse
Mutation name: type: null mutation fertility: subfertile Comment: Transcription-driven DNA methylation setting on the mouse Peg3 locus. Bretz CL et al. (2017) The imprinting of the mouse Peg3 domain is controlled through the Peg3-DMR, which obtains its maternal-specific DNA methylation during oogenesis. In the current study, we deleted an oocyte-specific alternative promoter, termed U1, which is localized 20 kb upstream of the Peg3-DMR. Deletion of this alternative promoter resulted in complete removal of the maternal-specific DNA methylation on the Peg3-DMR. Consequently, the imprinted genes in the Peg3 domain become biallelic in the mutants with maternal transmission of the deletion. Expression levels of the imprinted genes were also affected in the mutants: 2-fold upregulation of Peg3 and Usp29 and downregulation of Zim1 to basal levels. Breeding experiments further indicated under-representation of females among the surviving mutants, a potential sex-biased outcome from the biallelic expression of the Peg3 domain. Overall, the results suggest that U1-driven transcription may be required for establishing oocyte-specific DNA methylation on the Peg3 domain.//////////////////