MEG3 (maternally expressed 3) is a maternally expressed, imprintedlong non-coding RNAgene.[1] At least 12 different isoforms of MEG3 are generated by alternative splicing.[2] Expression of MEG3 is lost in cancer cells.[2][3] It acts as a growth suppressor in tumour cells, and activates p53.[3][4] A 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]
↑ 3.03.1Zhang 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. PMID14602737.
↑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. PMID17569660.
↑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. PMID10759892.
Further reading
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. PMID16793321.
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. PMID14702039.