MEG3 (maternally expressed 3) is a maternally expressed, imprinted long non-coding RNA gene. At least 12 different isoforms of MEG3 are generated by [1 ] alternative splicing. Expression of MEG3 is lost in cancer cells. [2 ] [2 ] It acts as a growth suppressor in [3 ] tumour cells, and activates p53. [3 ] A [4 ] pituitary transcript variant has been associated with inhibited cell proliferation. Studies in mouse and sheep suggest that an upstream intergenic differentially methylated region ( IG-DMR) regulates imprinting of the region. The expression profile in mouse of the co-regulated Meg3 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. [5 ]
See also [ edit ]
References [ edit ]
^ "Entrez Gene: MEG3 maternally expressed 3".
^ a b Zhang X, Rice K, Wang Y et al. (March 2010). "Maternally expressed gene 3 (MEG3) noncoding ribonucleic acid: isoform structure, expression, and functions". Endocrinology 151 (3): 939–47. doi: 10.1210/en.2009-0657. PMC 2840681. PMID 20032057.
^ a b Zhang X, Zhou Y, Mehta KR et al. (November 2003). "A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells". J. Clin. Endocrinol. Metab. 88 (11): 5119–26. doi: 10.1210/jc.2003-030222. PMID 14602737.
^ Zhou Y, Zhong Y, Wang Y et al. (August 2007). "Activation of p53 by MEG3 non-coding RNA". J. Biol. Chem. 282 (34): 24731–42. doi: 10.1074/jbc.M702029200. PMID 17569660.
^ Miyoshi N, Wagatsuma H, Wakana S, Shiroishi T, Nomura M, Aisaka K, Kohda T, Surani MA, Kaneko-Ishino T, Ishino F (Aug 2000). "Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q". Genes Cells 5 (3): 211–20. doi: 10.1046/j.1365-2443.2000.00320.x. PMID 10759892.
Further reading [ edit ]
Zhao J, Zhang X, Zhou Y et al. (2006). "Cyclic AMP stimulates MEG3 gene expression in cells through a cAMP-response element (CRE) in the MEG3 proximal promoter region". Int. J. Biochem. Cell Biol. 38 (10): 1808–20. doi: 10.1016/j.biocel.2006.05.004. PMID 16793321.
Kimura K, Wakamatsu A, Suzuki Y et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi: 10.1101/gr.4039406. PMC 1356129. PMID 16344560.
Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285. PMID 14702039.
Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi: 10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Yu W, Andersson B, Worley KC et al. (1997). "Large-scale concatenation cDNA sequencing". Genome Res. 7 (4): 353–8. doi: 10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
Andersson B, Wentland MA, Ricafrente JY et al. (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi: 10.1006/abio.1996.0138. PMID 8619474.