H19 antisense RNA can up-regulate igf2 transcription by activation of a novel promoter in mouse myoblasts

Tran, V. G.; Court, F.; Duputie, A.; Antoine, E.; Aptel, N.; Milligan, L.; Carbonell, F.; Lelay-Taha, M. N.; Piette, J.; Weber, M.; Montarras, D.; Pinset, C.; Dandolo, L.; Forne, T.; Cathala, G.

PLoS One

2012 / vol 7 / pages e37923


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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10.1371/journal.pone.0037923 PONE-D-12-05035 [pii]

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