Imprinting of IGF2 P0 transcript and novel alternatively spliced INS-IGF2 isoforms show differences between mouse and human

Monk, David and Sanches, R. and Arnaud, Philippe and Apostolidou, S. and Hills, Frank and Abu-Amero, S. and Murrell, A. and Friess, H. and Reik, W. and Stanier, Philip (2006) Imprinting of IGF2 P0 transcript and novel alternatively spliced INS-IGF2 isoforms show differences between mouse and human. Human Molecular Genetics, 15 (8). pp. 1259-1269. ISSN 0964-6906

Full text is not in this repository.

Official URL: http://hmg.oxfordjournals.org/cgi/content/full/15/...

This item is available in the Library Catalogue

Abstract

Genomic imprinting is limited to a subset of genes that play critical roles in fetal growth, development and behaviour. One of the most studied imprinted genes encodes insulin-like growth factor 2, and aberrant imprinting and DNA methylation of this gene is associated with the growth disorders Beckwith–Wiedemann and Silver–Russell syndromes and many human cancers. Specific isoforms of this gene have been shown to be essential for normal placental function, as mice carrying paternal null alleles for the Igf2-P0 transcript are growth restricted at birth. We report here the identification of three novel human transcripts from the IGF2 locus. One is equivalent to the mouse Igf2-P0 transcript, whereas the two others (INSIGF long and short) originate from the upstream INS gene that alternatively splices to downstream IGF2 exons. In order to elucidate the molecular mechanisms involved in the complex imprinting of these novel IGF2 transcripts, both the allele-specific expression and methylation for all the IGF2 promoters including P0 and the INSIGF transcripts were analysed in human tissues. Similar to the mouse, the human IGF2-P0 transcript is paternally expressed; however, its expression is not limited to placenta. This expression correlates with tissue-specific promoter methylation on the maternal allele. The two novel INSIGF transcripts reported here use the INS promoter and show highly restricted tissue expression profiles including the pancreas. As previously reported for INS in the yolk sac, we demonstrate complex, tissue-specific imprinting of these transcripts. The finding of additional transcripts within this locus will have important implications for IGF2 regulation in both cancer and metabolism.

Item Type:Article
Additional Information:

PubMed PMID: 16531418.

Research Areas:School of Science and Technology > Natural Sciences
Citations on ISI Web of Science:43
ID Code:2498
Useful Links:
Deposited On:17 Jun 2009 12:04
Last Modified:03 Feb 2014 08:17

Repository staff only: item control page

Full text downloads (NB count will be zero if no full text documents are attached to the record)

Downloads per month over the past year