First Author | Tran VG | Year | 2012 |
Journal | PLoS One | Volume | 7 |
Issue | 5 | Pages | e37923 |
PubMed ID | 22662250 | Mgi Jnum | J:187302 |
Mgi Id | MGI:5436174 | Doi | 10.1371/journal.pone.0037923 |
Citation | Tran VG, et al. (2012) H19 antisense RNA can up-regulate Igf2 transcription by activation of a novel promoter in mouse myoblasts. PLoS One 7(5):e37923 |
abstractText | It was recently shown that a long non-coding RNA (lncRNA), that we named the 91H RNA (i.e. antisense H19 transcript), is overexpressed in human breast tumours and contributes in trans to the expression of the Insulin-like Growth Factor 2 (IGF2) gene on the paternal chromosome. Our preliminary experiments suggested that an H19 antisense transcript having a similar function may also be conserved in the mouse. In the present work, we further characterise the mouse 91H RNA and, using a genetic complementation approach in H19 KO myoblast cells, we show that ectopic expression of the mouse 91H RNA can up-regulate Igf2 expression in trans despite almost complete unmethylation of the Imprinting-Control Region (ICR). We then demonstrate that this activation occurs at the transcriptional level by activation of a previously unknown Igf2 promoter which displays, in mouse tissues, a preferential mesodermic expression (Pm promoter). Finally, our experiments indicate that a large excess of the H19 transcript can counteract 91H-mediated Igf2 activation. Our work contributes, in conjunction with other recent findings, to open new horizons to our understanding of Igf2 gene regulation and functions of the 91H/H19 RNAs in normal and pathological conditions. |