Imprinting of PEG3, the Human Homologue of a Mouse Gene Involved in Nurturing Behavior

doi:10.1006/geno.2000.6419

Genomics

Volume 71, Issue 1, 1 January 2001, Pages 110-117

https://doi.org/10.1006/geno.2000.6419 Get rights and content

Abstract

The paternally expressed Peg3 gene in mice encodes an unusual Krüppel-type zinc finger protein implicated in critical cellular and behavioral functions including growth, apoptosis, and maternal nurturing behavior. Methylation and expression analyses were used to determine whether PEG3 on chromosome 19q13.4 is imprinted in humans. The PEG3 promoter is encompassed within a large CpG-rich region that is differentially methylated in fetal tissues. Furthermore, expression studies demonstrate that PEG3 is ubiquitously imprinted throughout development and postnatally. Multiple isoforms of the PEG3 gene, including a novel transcript, are paternally expressed. These results are the first to show that human chromosome 19q13.4 contains an imprinted region. The imprinted status of PEG3 throughout life coupled with its neural expression and putative roles in regulating cell growth suggests that PEG3 may be a susceptibility locus for cancer as well as neurobehavioral deficits.

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In this study, we performed the first systematic survey of DNA methylation status of the CpG islands of the PEG3 (Paternally expressed gene 3) imprinted domain in the mouse, cow, and human genomes. Previous studies have shown that the region surrounding the first exon of PEG3 contains a differentially methylated CpG island. In addition, we have discovered two previously unreported differentially methylated regions (DMR): one in the promoter region of mouse Zim3 and another in the promoter region of human USP29. In the cow, the Peg3-CpG island was the only area that showed DMR status. We have also examined the methylation status of several CpG islands in this region using human tumor-derived DNA. The CpG islands near PEG3 and USP29 both showed hypermethylation in DNA derived from breast and ovarian tumors. Overall, this study shows that the PEG3 imprinted domain of humans, cows, and mice contains differing numbers of DMRs, but the PEG3-CpG island is the only DMR that is conserved among these three species.
Loss of methylation imprint of Snrpn in postovulatory aging mouse oocyte
2008, Biochemical and Biophysical Research Communications
Prolonged residence of postovulatory oocyte in the oviduct or prolonged culture in vitro can lead to oocyte aging, which significantly affects pre- and post-implantation embryo development. In this study, we employed bisulfite sequencing and COBRA methods to investigate the DNA methylation status of differentially methylated regions (DMRs) of Snrpn and Peg1/Mest, two maternally imprinted genes, in postovulatory oocytes aged in vivo and in vitro. The results showed that Snrpn DMR was clearly demethylated in oocytes aged in vivo at 29 h post-hCG and in denuded oocytes aged in vitro for the same time period. However, Peg1/Mest did not show any demethylation in all aged groups at 29 h post-hCG. These data indicate that oocytes undergo time-dependent demethylation of Snrpn DMR during the process of postovulatory aging.
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Mouse Peg3 is a paternally expressed gene. Study of methylation of the Peg3 gene in P19 embryonal carcinoma cells suggested that monoallelic methylation of CpG dinucleotides is not only present in the promoter region, but also in the first exon and the first intron. Promoter activity analysis demonstrated that the minimal promoter of the Peg3 gene is located in the region between − 827 and + 712 and the critical region for promoter activity is between + 423 and + 712. We further identified the roles of the cis-elements, conserved sequence element (CSE) and YY1-binding sites, in the regulation of Peg3 expression and found that CSE is involved in the inhibition of Peg3 expression, while YY1-binding sites serve as activating cis-elements to antagonize CSE-mediated inhibition.
Diploid parthenogenetic embryos adopt a maternal-type methylation pattern on both sets of maternal chromosomes
2008, Genomics
Epigenetic modifications are closely associated with embryo developmental potential. One of the epigenetic modifications thought to be involved in genomic imprinting is DNA methylation. Here we show that the maternally imprinted genes Snrpn and Peg1/Mest were nearly unmethylated or heavily methylated, respectively, in their differentially methylated regions (DMRs) at the two-cell stage in parthenogenetic embryos. However, both genes were gradually de novo methylated, with almost complete methylation of all CpG sites by the morula stage in parthenogenetic embryos. Unexpectedly, another maternally imprinted gene, Peg3, showed distinct dynamics of methylation during preimplantation development of diploid parthenogenetic embryos. Peg3 showed seemingly normal methylation patterns at the two-cell and morula stages, but was also strongly de novo methylated in parthenogenetic blastocysts. In contrast, the paternally imprinted genes H19 and Rasgrf1 showed complete unmethylation of their DMRs at the morula stage in parthenogenetic embryos. These results indicate that diploid parthenogenetic embryos adopt a maternal-type methylation pattern on both sets of maternal chromosomes and that the aberrantly homogeneous status of methylation imprints may partially account for developmental failure.
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¹: To whom correspondence should be addressed at Box 3433, Duke University Medical Center, Durham, NC 27710. Telephone: (919) 684-2770. Fax: (919) 684-5584. E-mail: [email protected]. Internet: URL, http://www.geneimprint.com

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Regular ArticleImprinting of PEG3, the Human Homologue of a Mouse Gene Involved in Nurturing Behavior

Abstract

Gynecol. Oncol.

Biochem. Biophys. Res. Commun.

Trends Cogn. Sci.

Methods

Mol. Cell.

Genomics

Genomics

Trends Genet.

FEBS Lett.

Curr. Opin. Genet. Dev.

Genomics

First clinical case of small de novo duplication of 19q (13.3–13.4) confirmed by FISH

Am. J. Med. Genet.

γ2-COP, a novel imprinted gene on chromosome 7q32, defines a new imprinting cluster in the human genome

Hum. Mol. Genet.

Organization and expression of eucaryotic split genes coding for proteins

Annu. Rev. Biochem.

A truncated human peroxisome proliferator-activated receptor alpha splice variant with dominant negative activity

Mol. Endocrinol.

Promoter-region hypermethylation and gene silencing in human cancer

Curr. Top. Microbiol. Immunol.

CpG-island methylation in aging and cancer

Curr. Top. Microbiol. Immunol.

Regular Article
Imprinting of PEG3, the Human Homologue of a Mouse Gene Involved in Nurturing Behavior