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

PLoS One. 2012;7(5):e37923. doi: 10.1371/journal.pone.0037923. Epub 2012 May 25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • DNA Methylation
  • Gene Expression Regulation*
  • Gene Order
  • Gene Silencing
  • Genomic Imprinting
  • Insulin-Like Growth Factor II / genetics*
  • Mice
  • Molecular Sequence Data
  • Myoblasts / metabolism*
  • Promoter Regions, Genetic*
  • RNA, Antisense / metabolism*
  • RNA, Long Noncoding / genetics*
  • Transcription Initiation Site
  • Transcription, Genetic
  • Transcriptional Activation*

Substances

  • H19 long non-coding RNA
  • RNA, Antisense
  • RNA, Long Noncoding
  • Insulin-Like Growth Factor II