MEG3

MEG3, or maternally expressed gene 3, is a long non-coding RNA gene located in the imprinted DLK1-DIO3 locus on human chromosome 14q32. The locus contains a cluster of maternally expressed noncoding RNAs and paternally expressed protein-coding genes. MEG3 is expressed predominantly from the maternal allele, while the paternal allele is silenced by DNA methylation at imprinting control regions, including the MEG3 differential methylated region. This imprinting pattern results in maternal-specific transcription of MEG3 transcripts that exist in multiple isoforms.

MEG3 functions as a regulatory RNA with roles in development and disease. It can influence gene expression by recruiting chromatin-modifying complexes such as PRC2 to target loci, contributing to epigenetic regulation. It also interacts with the p53 signaling pathway to promote p53-dependent transcription, cell cycle arrest, and apoptosis. Additionally, MEG3 can act as a competing endogenous RNA, binding multiple microRNAs and modulating their targets, thereby affecting pathways related to proliferation and differentiation. MEG3 transcripts are found in both the nucleus and cytoplasm, with tissue-specific expression patterns.

Biological roles attributed to MEG3 include involvement in neural and placental development and in the regulation of stem cell differentiation and pluripotency. In humans, reduced MEG3 expression has been reported in a variety of cancers, including gliomas and hepatocellular carcinoma, where loss of MEG3 is associated with increased tumor growth and poorer prognosis. Changes in MEG3 methylation or expression are studied as potential biomarkers and therapeutic targets.

In mice, Meg3 (Gtl2) is the ortholog within the corresponding imprinted cluster and shares similar regulatory features and functional associations with development and tumor suppression.