Journal Article

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

Forné, Thierry, Aptel, Nathalie, Duputié, Anne, Piette, Jacques, Lelay-Taha, Marie-Noëlle, Court, Franck, Carbonell, Françoise, Antoine, Etienne, Montarras, Didier, Milligan, Laura, Weber, Michaël, Tran, Van Giang, Pinset, Christian, Cathala, Guy, Dandolo, Luisa

2012

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Antisense RNA / Base Sequence / Biochemistry, Molecular Biology / Biology / Breast cancer / Chromosomes / Complementation / DNA Methylation / Ectopic expression / Experiments / Gene expression / Gene Expression Regulation / Gene Order / Gene regulation / Gene Silencing / Genes / Genomes / Genomic Imprinting / Genomics / Imprinting / Insulin / Insulin-like growth factor II / Insulin-Like Growth Factor II - genetics / Insulin-like growth factors / Life Sciences / Mice / Molecular Sequence Data / Myoblasts / Myoblasts - metabolism / Non-coding RNA / Polymerase chain reaction / Promoter Regions, Genetic / Ribonucleic acid / RNA / RNA polymerase / RNA, Antisense - metabolism / RNA, Long Noncoding - genetics / Tissues / Transcription (Genetics) / Transcription activation / Transcription Initiation Site / Transcription, Genetic / Transcriptional Activation / Tumors