title: Identification of methylation-dependent regulatory elements for intergenic miRNAs in human H4 cells.
abstract: MicroRNAs (miRNAs) are important post-transcriptional regulators of various biological processes. Although our knowledge of miRNA expression and regulation has been increased considerably in recent years, the regulatory elements for miRNA gene expression (especially for intergenic miRNAs) are not fully understood. In this study, we identified differentially methylated regions (DMRs) within 1000 bp upstream from the start site of intergenic miRNAs in human neuroglioma cells using microarrays. Then we identified a unique sequence pattern, C[N](6)CT, within the DMRs using motif analysis. Interestingly, treatment of cells with a methyl transferase inhibitor (5-aza-2-deoxycytidine, DAC) significantly increased expression of miRNA genes with a high frequency of the C[N](6)CT motif in DMRs. Statistical analysis showed that the frequency of the C[N](6)CT motif in DMRs is highly correlated with intergenic miRNA gene expression, suggesting that C[N](6)CT motifs associated with DNA methylation regions play a role as regulatory elements for intergenic miRNA gene expression.
authors.affiliation: Division of Bioinformatics and Bio-Medical Informatics, Center for Genome Science, National Institute of Health, Republic of Korea.
authors.forename: Kwang Hee
authors.initials: KH
authors.lastname: Lee
authors.forename: Hyunyoung
authors.initials: H
authors.lastname: Kim
authors.forename: Byeong Jae
authors.initials: BJ
authors.lastname: Lee
authors.forename: Kiejung
authors.initials: K
authors.lastname: Park
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D021901:DNA, Intergenic; D000077209:Decitabine; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D050436:Regulatory Elements, Transcriptional; D017422:Sequence Analysis, DNA
chemical_list: D021901:DNA, Intergenic; D035683:MicroRNAs; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine