H19 antisense RNA can up-regulate Igf2 transcription by activation of a novel promoter in mouse myoblasts.
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.
Institut de Génétique Moléculaire de Montpellier, UMR 5535 CNRS-Université Montpellier II, Montpellier, France.
Van Giang
VG
Tran
Franck
F
Court
Anne
A
Duputié
Etienne
E
Antoine
Nathalie
N
Aptel
Laura
L
Milligan
Françoise
F
Carbonell
Marie-Noëlle
MN
Lelay-Taha
Jacques
J
Piette
Michaël
M
Weber
Didier
D
Montarras
Christian
C
Pinset
Luisa
L
Dandolo
Thierry
T
Forné
Guy
G
Cathala
D000818:Animals; D001483:Base Sequence; D019175:DNA Methylation; D005786:Gene Expression Regulation; D023061:Gene Order; D020868:Gene Silencing; D018392:Genomic Imprinting; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D032446:Myoblasts / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016372:RNA, Antisense / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics*; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D015533:Transcriptional Activation
C094335:H19 long non-coding RNA; D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D007335:Insulin-Like Growth Factor II