| First Author | Chavali PL | Year | 2011 |
| Journal | Nucleic Acids Res | Volume | 39 |
| Issue | 16 | Pages | 6908-18 |
| PubMed ID | 21586588 | Mgi Jnum | J:183067 |
| Mgi Id | MGI:5317404 | Doi | 10.1093/nar/gkr303 |
| Citation | Chavali PL, et al. (2011) Cis-regulation of microRNA expression by scaffold/matrix-attachment regions. Nucleic Acids Res 39(16):6908-18 |
| abstractText | microRNAs (miRNAs) spatio-temporally modulate gene expression; however, very little is known about the regulation of their expression. Here, we hypothesized that the well-known cis-regulatory elements of gene expression, scaffold/matrix-attachment regions (MARs) could modulate miRNA expression. Accordingly, we found MARs to be enriched in the upstream regions of miRNA genes. To determine their role in cell type-specific expression of miRNAs, we examined four individual miRNAs (let-7b, miR-17, miR-93 and miR-221) and the miR-17-92 cluster, known to be overexpressed in neuroblastoma. Our results show that MARs indeed define the cell-specific expression of these miRNAs by tethering the chromatin to nuclear matrix. This is brought about by cell type-specific binding of HMG I/Y protein to MARs that then promotes the local acetylation of histones, serving as boundary elements for gene activation. The binding, chromatin tethering and gene activation by HMG I/Y was not observed in fibroblast control cells but were restricted to neuroblastoma cells. This study implies that the association of MAR binding proteins to MARs could dictate the tissue/context specific regulation of miRNA genes by serving as a boundary element signaling the transcriptional activation. |
