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Publication : H19 antisense RNA can up-regulate Igf2 transcription by activation of a novel promoter in mouse myoblasts.

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.
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