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since 01/2001:

maternally expressed 3 (non-protein coding) OKDB#: 4290
 Symbols: MEG3 Species: human
 Synonyms: GTL2, FP504, prebp1, PRO0518, PRO2160, FLJ31163, FLJ42589, NCRNA00023,  Locus: 14q32 in Homo sapiens

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General Comment NCBI Summary: MEG3 is a maternally expressed imprinted gene which appears to function as an RNA molecule; multiple splice variants are observed in the available sequence data and a pituitary transcript variant has been associated with inhibited cell proliferation. Studies in mouse and sheep suggest that an upstream intergenic differentially methylated region regulates imprinting of the region. The expression profile in mouse of the co-regulated Meg3/Gtl2 and Dlk1 genes suggests a causative role in the pathologies found in uniparental disomy animals, characterized by defects in skeletal muscle maturation, bone formation, placenta size and organization, and prenatal lethality. The sheep homolog is associated with the callipyge mutation which in heterozygous individuals affects a muscle-specific long-range control element located in the DLK1-GTL2 intergenic region and results in the callipyge muscular hypertrophy. The non-Mendelian inheritance pattern, known as polar overdominance, likely results from the combination of the cis-effect on the expression levels of genes in the DLK1-GTL2 imprinted domain, and trans interaction between the products of reciprocally imprinted genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq]
General function Cell proliferation
Cellular localization
Ovarian function Early embryo development
Comment Human in vitro oocyte maturation is not associated with increased imprinting error rates at LIT1, SNRPN, PEG3 and GTL2. Kuhtz J 2014 et al. STUDY QUESTION Does in vitro maturation (IVM) of cumulus-enclosed germinal vesicle (GV) stage oocytes retrieved from small antral follicles in minimally stimulated cycles without an ovulatory hCG dose induce imprinting errors at LIT1, SNRPN, PEG3 and GTL2 in human oocytes? SUMMARY ANSWER There is no significant increase in imprinting mutations at LIT1, SNRPN, PEG3 and GTL2 after IVM of cumulus-enclosed GV oocytes from small antral follicles in minimally stimulated cycles without hCG priming. WHAT IS KNOWN ALREADY Animal models have generally demonstrated correct methylation imprint establishment for in vitro grown and matured oocytes. For human IVM, well-designed studies allowing conclusions on imprint establishment are currently not available. STUDY DESIGN, SIZE, DURATION Immature oocyte-cumulus complexes from 2 to 9 mm follicles were retrieved in polycystic ovary syndrome (PCOS) subjects in minimally stimulated cycles without hCG priming and matured in vitro. In vivo grown oocytes were retrieved after conventional ovarian stimulation for IVF/ICSI or after ovulation induction. Imprinting error rates at three maternally methylated (LIT1, SNRPN and PEG3) and one paternally methylated (GTL2) imprinted genes were compared in 71 in vitro and 38 in vivo matured oocytes. PARTICIPANTS/MATERIALS, SETTING, METHODS The limiting dilution bisulfite sequencing technique was applied, allowing increased sensitivity based on multiplex PCR for the imprinted genes and the inclusion of non-imprinted marker genes for cumulus cell DNA contamination. MAIN RESULTS AND THE ROLE OF CHANCE In vitro as well as in vivo matured oocytes showed only a few abnormal alleles, consistent with epimutations. The abnormalities were more frequent in immature than in mature oocytes for both groups, although no significant difference was reached. There was no statistically significant increase in imprinting errors in IVM oocytes. LIMITATIONS, REASONS FOR CAUTION This single cell methylation analysis was restricted to a number of well-selected imprinted genes. Genome-wide methylation analysis of single human oocytes is currently not possible. WIDER IMPLICATIONS OF THE FINDINGS IVM is a patient-friendly alternative to conventional ovarian stimulation in PCOS patients and is associated with reduced gonadotrophin costs and avoidance of OHSS. The results of this study show for the first time that optimized human IVM procedures have no significant effects on the establishment of maternal DNA methylation patterns at LIT1, SNRPN, PEG3 and GTL2. STUDY FUNDING/COMPETING INTERESTS This study was supported by research funds from Agentschap voor Innovatie door Wetenschap en Technologie (IWT-TBM 110680), Wetenschappelijk Fonds Willy Gepts (WFWG 2011) and German Research Foundation (HA 1374/12-2). There are no competing interests. /////////////////////////
Expression regulated by
Ovarian localization Oocyte, Ovarian tumor
Comment Promoter hypermethylation influences the suppressive role of maternally expressed?3, a long non-coding RNA, in the development of epithelial ovarian cancer. Sheng X 2014 et al. Maternally expressed?3 (MEG3) is a long non-coding RNA that can activate p53 and inhibit tumorigenesis and progression of various types of cancers. However, the role of MEG3 in epithelial ovarian cancer (EOC) is still unknown. The aim of the present study was to confirm whether MEG3 is downregulated in human EOC, determine its possible mechanism of action and elucidate the role of MEG3 in EOC. Differences in the expression of MEG3 and in the methylation status of the MEG3 promoter between EOC and normal ovary were analyzed using RT-PCR and methylation-specific PCR (MSP), respectively. MTT and EdU assays and flow cytometric analysis were used to assess the growth of ovarian cancer cells after overexpression of MEG3. The target genes regulated by MEG3 were detected with the Dual Luciferase Reporter system. The expression levels of target genes were confirmed using RT-PCR and western blotting. In contrast to normal ovarian tissues, the expression of MEG3 was absent or decreased in most EOC tissues as well as in human EOC cell lines, and the promoter of the MEG3 gene was highly methylated in both cancer tissues and cell lines. Treatment with 5-aza-2-deoxycytidine reversed the promoter hypermethylation and increased MEG3 expression. In addition, ectopic expression of MEG3 suppressed the proliferation and growth of OVCAR3 cells and promoted apoptosis. Finally, MEG3 activated p53 in OVCAR3 cells. In conclusion, our data suggest that MEG3 is epigenetically silenced in EOC due to promoter hypermethylation, which may contribute to the development of EOC. /////////////////////////
Follicle stages
Mutations 0 mutations
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created: May 11, 2010, 1:30 p.m. by: hsueh   email:
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last update: July 2, 2014, 11:43 a.m. by: hsueh    email:

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