Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms' tumour
Nature GeneticsPublished 1 July 1994
Marja Steenman, Shirley Rainier, Craig J. Dobry, Paul Grundy, Isabelle L. Horon, Andrew P. Feinberg
Citations464
SJR quartileQ1
SJR score16.59
SNIP6.64
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TL;DR
The data suggest an epigenetic mechanism for inactivation of H19 as a tumour suppressor gene through imprinting of a large domain of the maternal chromosome, which results in a reversal to a paternal epigenotype.
Abstract
The insulin-like growth factor-II (IGF2) and H19 genes are imprinted in mouse and human, with expression of the paternal IGF2 and maternal H19 alleles. IGF2 undergoes loss of imprinting (LOI) in most Wilms' tumours (WT). We now show that: (i) LOI of IGF2 is associated with a 80-fold down regulation of H19 expression; (ii) these changes are associated with alterations in parental-origin-specific, tissue-independent sites of DNA methylation in the H19 promoter; and (iii) loss of heterozygosity is also associated with loss of H19 expression. Thus, imprinting of a large domain of the maternal chromosome results in a reversal to a paternal epigenotype. These data also suggest an epigenetic mechanism for inactivation of H19 as a tumour suppressor gene.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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