Epigenetic regulation of the Igf2/H19 gene cluster

M. Nordin, D. Bergman, M. Halje, W. Engström, A. Ward

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Igf2 (insulin-like growth factor 2) and H19 genes are imprinted in mammals; they are expressed unevenly from the two parental alleles. Igf2 is a growth factor expressed in most normal tissues, solely from the paternal allele. H19 gene is transcribed (but not translated to a protein) from the maternal allele. Igf2 protein is a growth factor particularly important during pregnancy, where it promotes both foetal and placental growth and also nutrient transfer from mother to offspring via the placenta. This article reviews epigenetic regulation of the Igf2/H19 gene-cluster that leads to parent-specific expression, with current models including parental allele-specific DNA methylation and chromatin modifications, DNA-binding of insulator proteins (CTCFs) and three-dimensional partitioning of DNA in the nucleus. It is emphasized that key genomic features are conserved among mammals and have been functionally tested in mouse. 'The enhancer competition model', 'the boundary model' and 'the chromatin-loop model' are three models based on differential methylation as the epigenetic mark responsible for the imprinted expression pattern. Pathways are discussed that can account for allelic methylation differences; there is a recent study that contradicts the previously accepted fact that biallelic expression is accompanied with loss of differential methylation pattern.
Original languageEnglish
Pages (from-to)189-199
Number of pages11
JournalCell Proliferation
Volume47
Issue number3
Early online date16 Apr 2014
DOIs
Publication statusPublished - Jun 2014

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    Nordin, M., Bergman, D., Halje, M., Engström, W., & Ward, A. (2014). Epigenetic regulation of the Igf2/H19 gene cluster. Cell Proliferation, 47(3), 189-199. https://doi.org/10.1111/cpr.12106