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PEG3 (paternally expressed 3)

Written2010-08Yinhua Yu, Weiwei Feng, Zhen Lu, Robert C Bast Jr
The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 354, Houston, TX 77030, USA

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Alias_symbol (synonym)ZKSCAN22
Other aliasDKFZp781A095
HGNC (Hugo) PEG3
LocusID (NCBI) 5178
Atlas_Id 41690
Location 19q13.43  [Link to chromosome band 19q13]
Location_base_pair Starts at 57321445 and ends at 57352094 bp from pter ( according to hg19-Feb_2009)  [Mapping PEG3.png]


  Figure A. PEG3 DNA located on chromosome 19, starts at 62013257 and ends at 62043906 bp.
Figure B. The PEG3 gene contains 7-10 exons with 5 different transcripts.
Figure C. PEG3 promoter and first exon. The transcription start site and direction are indicated with an arrow. The horizontal bars are 32 CpG sites. The dark blue box is a CpG island surrounded the first exon (Figure modified from Feng et al., 2008).
Description Human PEG3 was originally identified as an ortholog of murine Peg3 that is the first imprinted gene detected in mouse chromosome 7. Human PEG3 is located ~2 Mb proximal of the 19q telomere, which is rich in Krüppel-type ZNF genes (Kim et al., 1997). Bisulfite sequencing across PEG3 revealed that all CpG dinucleotides examined were differentially methylated in human fetal brain, kidney, liver, and pancreas. PEG3 is monoallelically expressed during fetal development, it is a maternal-imprinted gene (Murphy et al., 2001).
Transcription The PEG3 gene contains 7-10 exons with 5 different transcripts.
Pseudogene There are no known pseudogenes, but an antisense transcript gene (APEG3), which is transcribed in the opposite direction of PEG3, has been identified from human. It is confirmed the presence of APEG3 in total RNAs from brain thalamus and testis. The functional significance of APEG3 is not known. The paternal allele-specific expression of anti-sense Peg3 (imprinting) was detected in mouse brain, but not in human yet (Choo et al., 2002).


Description PEG3 is maternal-imprinted and paternally expressed. The imprinted status of PEG3 throughout development and adult life. PEG3 may be a susceptibility locus for cancer and for neurobehavioral deficits (Murphy et al., 2001).
Expression PEG3 is expressed at higher levels in ovary and placenta (Kim et al., 1997; Hiby et al., 2001). It was also strongly expressed in the adult brain (Kohda et al., 2001).
Localisation High levels of PEG3 have localized to the layer of villous cytotrophoblast cells in the human placenta, PEG3 expression is also detected in the ovary stroma (Hiby et al., 2001).
Function PEG3 is an imprinted gene expressed exclusively from the paternal allele. The precise function of PEG3 is not clear, but recent evidence suggests that it plays an important role in the p53/c-myc-mediated apoptosis pathway.
PEG3 is a maternally imprinted tumor suppressor gene that is downregulated in gliomas, ovarian cancers, breast cancers and other gynecologic cancers (Kohda et al., 2001; Dowdy et al., 2005; Feng et al., 2008).
There are several studies revealed murine Peg3 acts as an intermediary between p53 and Bax in a cell death pathway activated by DNA damage in primary mouse cortical neurons, inhibiting Peg3 activity blocks p53-induced apoptosis (Johnson et al., 2002). Pw1/Peg3 interacts with a p53-inducible gene product Siah1a. Coexpression of Pw1/Peg3 with Siah1a induces apoptosis independently of p53. Inhibiting Pw1/Peg3 activity blocks p53-induced apoptosis (Relaix et al., 2000). Since human PEG3 is highly conserved with murine Peg3, PEG3 may have same function, Jiang et al. (2010) demonstrated that enforced overexpression of PEG3 mRNA during zebrafish embryogenesis decreased beta-catenin protein expression and inhibited Wnt-dependent tail development. Peg3/Pw1 also inhibited Wnt signaling in human cells by binding to beta-catenin and promoting its degradation via a p53/Siah1-dependent, GSK3beta-independent proteasomal pathway. Hypermethylation of the PEG3 promoter in primary human gliomas led to a loss of imprinting and decreased PEG3 mRNA expression that correlated with increasing tumor grade (Jiang et al., 2010).
The transcription factor YY1 can bind to the first intron of human PEG3, and specifically to the paternal allele of the gene. YY1-binding sites are methylated only on the maternal chromosome. YY1-binding region may function as a methylation-sensitive insulator that could influence the imprinted expression of PEG3 (Kim et al., 2003).
Homology Human PEG3 is known to have orthologs in mice and cow. Human PEG3 gene sequences revealed a high level of conservation with Murine Peg3 (83% similarity), but one of the two proline-rich repeats is absent from the human PEG3 (Kim et al., 1997).


Note Mutations have not been detected.

Implicated in

Entity Glioma, glioblastoma
Note A significant decrease in PEG3 expression was more commonly observed in glioma cell lines as compared with that in primary cultures of astrocytes. Transfection of PEG3 cDNA in a glioma cell line resulted in a loss of tumorigenicity in nude mice (Kohda et al., 2001). The epigenetic silencing of PEG3 expression in glioma cell lines depends on aberrant DNA methylation of an exonic CpG island. Treatment of glioma cell lines with the DNA demethylating agent 5-aza-2'-deoxycytidine reversed the silencing of PEG3 biallelically (Maegawa et al., 2001). Re-expression of PEG3 in glioma cells suppresses their proliferation. Hypermethylation of the PEG3 promoter in primary human gliomas led to a loss of imprinting and decreased PEG3 mRNA expression that correlated with tumor grade (Jiang et al., 2010). The lower gene expression was confirmed statistically in glioblastoma (Otsuka et al., 2009).
Entity Endometrial cancer, cervical cancer, choriocarcinomas
Note PEG3 is silenced in all endometrial and cervical cancer cell lines studied. In contrast, loss of maternal imprinting and relatively high PEG3 expression levels were detected in all four choriocarcinomas cell lines studied (Dowdy et al., 2005).
Entity Breast cancer, ovarian cancer
Note Five of the eight ovarian cancer cell lines were found to be PEG3 negative, the remaining three express low levels of PEG3 mRNA (Dowdy et al., 2005). PEG3 was down-regulated in 75% of ovarian cancers. PEG3 was hypermethylated in 11 of 42 ovarian cancers (26%), and PEG3 expression was down-regulated in 10 of those 11 cancers. LOH was detected in 5 of 25 informative cases for PEG3 (20%). Re-expression of PEG3 markedly inhibited ovarian cancer growth. PEG3 expression could be restored by treatment with 5-aza-2'-deoxycytidine and trichostatin A (Feng et al., 2008).
Entity Hydatidiform moles
Note PEG3 is not mutated in women with familial recurrent hydatidiform moles, there is allele-specific methylation of the CpG island and expression from the paternal allele in two independent informative pedigrees (Van den Veyver et al., 2001).


Imprinting of an evolutionarily conserved antisense transcript gene APeg3.
Choo JH, Kim JD, Kim J.
Gene. 2008 Feb 15;409(1-2):28-33. Epub 2007 Nov 21.
PMID 18166281
Biallelic methylation and silencing of paternally expressed gene 3 (PEG3) in gynecologic cancer cell lines.
Dowdy SC, Gostout BS, Shridhar V, Wu X, Smith DI, Podratz KC, Jiang SW.
Gynecol Oncol. 2005 Oct;99(1):126-34.
PMID 16023706
Imprinted tumor suppressor genes ARHI and PEG3 are the most frequently down-regulated in human ovarian cancers by loss of heterozygosity and promoter methylation.
Feng W, Marquez RT, Lu Z, Liu J, Lu KH, Issa JP, Fishman DM, Yu Y, Bast RC Jr.
Cancer. 2008 Apr 1;112(7):1489-502.
PMID 18286529
Paternal monoallelic expression of PEG3 in the human placenta.
Hiby SE, Lough M, Keverne EB, Surani MA, Loke YW, King A.
Hum Mol Genet. 2001 May 1;10(10):1093-100.
PMID 11331620
The imprinted gene PEG3 inhibits Wnt signaling and regulates glioma growth.
Jiang X, Yu Y, Yang HW, Agar NY, Frado L, Johnson MD.
J Biol Chem. 2010 Mar 12;285(11):8472-80. Epub 2010 Jan 11.
PMID 20064927
Peg3/Pw1 is a mediator between p53 and Bax in DNA damage-induced neuronal death.
Johnson MD, Wu X, Aithmitti N, Morrison RS.
J Biol Chem. 2002 Jun 21;277(25):23000-7. Epub 2002 Apr 9.
PMID 11943780
The human homolog of a mouse-imprinted gene, Peg3, maps to a zinc finger gene-rich region of human chromosome 19q13.4.
Kim J, Ashworth L, Branscomb E, Stubbs L.
Genome Res. 1997 May;7(5):532-40.
PMID 9149948
Methylation-sensitive binding of transcription factor YY1 to an insulator sequence within the paternally expressed imprinted gene, Peg3.
Kim J, Kollhoff A, Bergmann A, Stubbs L.
Hum Mol Genet. 2003 Feb 1;12(3):233-45.
PMID 12554678
Tumour suppressor activity of human imprinted gene PEG3 in a glioma cell line.
Kohda T, Asai A, Kuroiwa Y, Kobayashi S, Aisaka K, Nagashima G, Yoshida MC, Kondo Y, Kagiyama N, Kirino T, Kaneko-Ishino T, Ishino F.
Genes Cells. 2001 Mar;6(3):237-47.
PMID 11260267
Epigenetic silencing of PEG3 gene expression in human glioma cell lines.
Maegawa S, Yoshioka H, Itaba N, Kubota N, Nishihara S, Shirayoshi Y, Nanba E, Oshimura M.
Mol Carcinog. 2001 May;31(1):1-9.
PMID 11398192
Imprinting of PEG3, the human homologue of a mouse gene involved in nurturing behavior.
Murphy SK, Wylie AA, Jirtle RL.
Genomics. 2001 Jan 1;71(1):110-7.
PMID 11161803
Aberrant promoter methylation and expression of the imprinted PEG3 gene in glioma.
Otsuka S, Maegawa S, Takamura A, Kamitani H, Watanabe T, Oshimura M, Nanba E.
Proc Jpn Acad Ser B Phys Biol Sci. 2009;85(4):157-65.
PMID 19367087
Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis.
Relaix F, Wei X, Li W, Pan J, Lin Y, Bowtell DD, Sassoon DA, Wu X.
Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2105-10.
PMID 10681424
The human homologue (PEG3) of the mouse paternally expressed gene 3 (Peg3) is maternally imprinted but not mutated in women with familial recurrent hydatidiform molar pregnancies.
Van den Veyver IB, Norman B, Tran CQ, Bourjac J, Slim R.
J Soc Gynecol Investig. 2001 Sep-Oct;8(5):305-13.
PMID 11677152


This paper should be referenced as such :
Yu, Y ; Feng, W ; Lu, Z ; Bast, RC Jr
PEG3 (paternally expressed 3)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(5):422-424.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)PEG3   8826
Entrez_Gene (NCBI)PEG3  5178  paternally expressed 3
AliasesPW1; ZKSCAN22; ZNF904; ZSCAN24
GeneCards (Weizmann)PEG3
Ensembl hg19 (Hinxton)ENSG00000198300 [Gene_View]  chr19:57321445-57352094 [Contig_View]  PEG3 [Vega]
Ensembl hg38 (Hinxton)ENSG00000198300 [Gene_View]  chr19:57321445-57352094 [Contig_View]  PEG3 [Vega]
ICGC DataPortalENSG00000198300
TCGA cBioPortalPEG3
AceView (NCBI)PEG3
Genatlas (Paris)PEG3
SOURCE (Princeton)PEG3
Genetics Home Reference (NIH)PEG3
Genomic and cartography
GoldenPath hg19 (UCSC)PEG3  -     chr19:57321445-57352094 -  19q13.4   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)PEG3  -     19q13.4   [Description]    (hg38-Dec_2013)
EnsemblPEG3 - 19q13.4 [CytoView hg19]  PEG3 - 19q13.4 [CytoView hg38]
Mapping of homologs : NCBIPEG3 [Mapview hg19]  PEG3 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AB003039 AB006625 AF208967 AF208968 AF208969
RefSeq transcript (Entrez)NM_001146184 NM_001146185 NM_001146186 NM_001146187 NM_006210
RefSeq genomic (Entrez)NC_000019 NC_018930 NG_012989 NT_011109 NW_004929415
Consensus coding sequences : CCDS (NCBI)PEG3
Cluster EST : UnigeneHs.731875 [ NCBI ]
CGAP (NCI)Hs.731875
Alternative Splicing GalleryENSG00000198300
Gene ExpressionPEG3 [ NCBI-GEO ]   PEG3 [ EBI - ARRAY_EXPRESS ]   PEG3 [ SEEK ]   PEG3 [ MEM ]
Gene Expression Viewer (FireBrowse)PEG3 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5178
GTEX Portal (Tissue expression)PEG3
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9GZU2   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9GZU2  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9GZU2
Splice isoforms : SwissVarQ9GZU2
Domaine pattern : Prosite (Expaxy)SCAN_BOX (PS50804)    ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domains : Interpro (EBI)C2H2_Znf_fam    Retrov_capsid_C    SCAN_dom    Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
Domain families : Pfam (Sanger)SCAN (PF02023)    zf-C2H2_6 (PF13912)   
Domain families : Pfam (NCBI)pfam02023    pfam13912   
Domain families : Smart (EMBL)SCAN (SM00431)  ZnF_C2H2 (SM00355)  
Conserved Domain (NCBI)PEG3
DMDM Disease mutations5178
Blocks (Seattle)PEG3
Structural Biology KnowledgeBase4BHX   
SCOP (Structural Classification of Proteins)4BHX   
CATH (Classification of proteins structures)4BHX   
Human Protein AtlasENSG00000198300
Peptide AtlasQ9GZU2
IPIIPI00478786   IPI00784928   IPI00646037   
Protein Interaction databases
IntAct (EBI)Q9GZU2
Ontologies - Pathways
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II transcription factor activity, sequence-specific DNA binding  nucleic acid binding  nucleus  nucleoplasm  cytoplasm  transcription, DNA-templated  apoptotic process  metal ion binding  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II transcription factor activity, sequence-specific DNA binding  nucleic acid binding  nucleus  nucleoplasm  cytoplasm  transcription, DNA-templated  apoptotic process  metal ion binding  
NDEx NetworkPEG3
Atlas of Cancer Signalling NetworkPEG3
Wikipedia pathwaysPEG3
Orthology - Evolution
GeneTree (enSembl)ENSG00000198300
Phylogenetic Trees/Animal Genes : TreeFamPEG3
Homologs : HomoloGenePEG3
Homology/Alignments : Family Browser (UCSC)PEG3
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPEG3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PEG3
Exome Variant ServerPEG3
ExAC (Exome Aggregation Consortium)PEG3 (select the gene name)
Genetic variants : HAPMAP5178
Genomic Variants (DGV)PEG3 [DGVbeta]
DECIPHER (Syndromes)19:57321445-57352094  ENSG00000198300
CONAN: Copy Number AnalysisPEG3 
ICGC Data PortalPEG3 
TCGA Data PortalPEG3 
Broad Tumor PortalPEG3
OASIS PortalPEG3 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPEG3  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPEG3
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PEG3
DgiDB (Drug Gene Interaction Database)PEG3
DoCM (Curated mutations)PEG3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PEG3 (select a term)
NCG5 (London)PEG3
Cancer3DPEG3(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry PEG3
NextProtQ9GZU2 [Medical]
Huge Navigator PEG3 [HugePedia]
snp3D : Map Gene to Disease5178
BioCentury BCIQPEG3
ClinGenPEG3 (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5178
Chemical/Pharm GKB GenePA33171
Clinical trialPEG3
canSAR (ICR)PEG3 (select the gene name)
PubMed28 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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