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© Research
Publication : PloS one

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in PloS one - 25 May 2012

Tran VG, Court F, Duputié A, Antoine E, Aptel N, Milligan L, Carbonell F, Lelay-Taha MN, Piette J, Weber M, Montarras D, Pinset C, Dandolo L, Forné T, Cathala G

Link to Pubmed [PMID] – 22662250

PLoS ONE 2012;7(5):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.