The mystique of epigenetic regulation: the remarkable case of a human noncoding RNA, nc886

nc886 is a regulatory noncoding RNA that is transcribed by RNA polymerase III (Pol III), is variably expressed in different biological contexts, and plays roles in inflammation and cancer. Epigenetic mechanisms play an intriguing role in regulating nc886 expression. As a maternally imprinted gene and metastable epiallele, nc866 exhibits polymorphic imprinting, with a methylation status that is influenced by environmental and biological factors. Consequently, the promoter DNA methylation status and the different resulting RNA expression levels of nc886 are associated with physiological and pathological conditions. In this review, we summarize the literature and explore the significance in relation to diverse roles of nc886. nc886 is transcribed by RNA polymerase III. nc886 binds to target proteins such as Protein Kinase R and Dicer to control their activities. nc886 has CpG islands in the promoter region, whose hypermethylation suppresses nc886 expression. CpG DNA methylation of nc886 is allele-specific. nc886 is a maternally imprinted gene. Imprinting of nc886 CpG DNA methylation is polymorphic; nc886 is imprinted in 75% of individuals but has both alleles unmethylated in the remaining 25%. nc886 is a metastable epiallele, whose CpG DNA methylation status is stochastically established and largely maintained during development. nc886 CpG DNA methylation in offspring is influenced by maternal factors including nutritional status, folic acid supplementation, age at conception and environmental factors. nc886 CpG DNA methylation is associated with several health traits. nc886 CpG DNA methylation is dysregulated in pathological conditions, with cancer being the most prominent example.