Disease relevance of Peg3

• Muscle cachexia is regulated by a p53-PW1/Peg3-dependent pathway [1].
• Peg3 encodes a C2H2 type zinc finger protein that is implicated in a novel physiological pathway regulating core body temperature, feeding behavior, and obesity in mice [2].
• Moreover, we found that p53 was co-localized with Peg3/Pw1 in brain ischemia/hypoxia by double staining analysis [3].

Psychiatry related information on Peg3

• However, this was not sufficient to rescue the maternal behavior phenotype seen in Peg3 deficient animals [4].

High impact information on Peg3

• We previously identified a gene Pw1, which encodes a large zinc-finger containing protein [5].
• Peg3/Pw1 is an imprinted gene involved in the TNF-NFkappaB signal transduction pathway [5].
• Peg3 imprinted gene on proximal chromosome 7 encodes for a zinc finger protein [6].
• Peg3 is expressed in early somites, branchial arches and other mesodermal tissues, as well as in the hypothalamus [6].
• In a systematic screen using subtraction hybridization between cDNAs from normal and parthenogenetic embryos, we initially identified two apparently novel imprinted genes, Peg1 and Peg3 [7].

Biological context of Peg3

• In analysis of a conserved region of proximal mouse chromosome 7 and human chromosome 19q, we have isolated a novel mouse gene, Zim1 (imprinted zinc-finger gene 1), encoding a typical Kruppel-type (C2H2) zinc-finger protein, located within 30 kb of a known imprinted gene, Peg3 (paternally expressed gene 3) [8].
• Gene Usp29 is located directly adjacent to Peg3 in a "head-to-head" orientation, and comprises exons distributed over a genomic distance of at least 400 kb [9].
• Imprinted expression was linked to the differential methylation of a region (DMR) upstream of the Peg3 gene [4].
• In one of the lines harboring one copy of the transgene, Peg3 was imprinted properly [4].
• To investigate the imprinting mechanism and gene expression of Peg3 and its neighboring gene(s), we used a 120 kb Peg3-containing BAC clone to generate transgenic mice [4].

Anatomical context of Peg3

• We identified regions in the maternally imprinted genes (Snrpn, Mest, and Peg3) that were unmethylated in sperm but 100% methylated in mature oocytes [10].
• To see whether the same situation would prevail in vivo, we have now determined the methylation status of H19 expressed from the maternal allele, and the expression and methylation status of a paternally expressed gene Peg3, in germ cells from sex-reversed and control embryos [11].
• No detectable levels of Peg3 mRNA were observed in two other androgen receptor-positive prostate tumor cell lines (MDA PCa-2a and -2b), and in the poorly differentiated and androgen receptor-negative prostate tumor lines PC-3 and DU-145 [12].
• Mest and Peg3, two imprinted genes that are paternally expressed, have been disrupted by gene targeting and show high levels of expression in regions where androgenetic cells accumulated, namely the hypothalamus, preoptic area and septum [13].
• Increased body fat in mice with a targeted mutation of the paternally expressed imprinted gene Peg3 [2].

Associations of Peg3 with chemical compounds

• Bisulfite sequencing revealed that reactivation of maternal alleles of Peg3 and Snrpn in specific tissues was accompanied by partial demethylation at their potential imprinting control regions [14].
• It is concluded that both androgens and loss of differentiation may affect the expression of Peg3, a mediator of the effects of TNF [12].
• Basal expression of Peg3 mRNA was almost completely abolished by the protein synthesis inhibitor cycloheximide [12].
• Experiments with Actinomycin D suggested that androgens act at a transcriptional level rather than by changing the stability of Peg3 mRNA [12].
• The steroid specificity of Peg3 mRNA regulation reflected the aberrant ligand specificity of the mutated androgen receptor in LNCaP cells, supporting the involvement of the androgen receptor in the repression process [12].

Other interactions of Peg3

• The imprinted gene Peg3 is not essential for tumor necrosis factor alpha signaling [15].
• The 5'-ends of two paternally expressed mouse genes, Peg3 and Usp29, are jointly associated with a CpG island that exhibits allele-specific methylation [16].
• Hierarchical clustering patterned specific expression of hChr21 gene dosage effects on neuron outgrowth, migration, and differentiation, such as Syngr2, Dncic2, Eif3sf, and Peg3 [17].
• Administration of exogenous leptin resulted in a significant reduction in food intake in wild-type mice that was not observed in Peg3+/- mutants [2].
• At present, the precise function of Pw1 is not understood; however, we note that Pw1 maps to the proximal region of chromosome 7 near the axial segmentation mutant pudgy which shows severe perturbation of axial skeletal and muscle structures [18].

Analytical, diagnostic and therapeutic context of Peg3

• The down-regulation of Peg3 mRNA by androgens was confirmed by Northern blot hybridization [12].
• In this study, we found that Peg3/Pw1 expression is enhanced in peri-ischemic neurons in rat stroke model by in situ hybridization analysis, where p53 expression was also induced by immunohistochemical analysis [3].

References