H19 Antisense RNA Can Up-Regulate Igf2 Transcription by Activation of a Novel Promoter in Mouse MyoblastsReportar como inadecuado




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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.



Autor: Van Giang Tran , Franck Court , Anne Duputié, Etienne Antoine, Nathalie Aptel, Laura Milligan, Françoise Carbonell, Marie-Noël

Fuente: http://plos.srce.hr/



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