Deletion of a Mesodernal Silencer in Igf2 Results in Biallelic Expression

Wolf Reik
Department of Development and Genetics; The Babraham Institute

Known imprinting controls for the mouse Igf2 gene are the endodermal enhancers near H19 and the differentially methylated region (DMR) upstream of H19 which may act as an insulator. However, the Igf2 gene itself has DMRs whose functions are unclear. DMR1 is upstream of the Igf2 gene and is paternally methylated in mesodermal but not endodermal tissues. Deletion of the DMR1 region results in biallelic expression of Igf2 in mesodermal but not endodermal tissues, and continued expression after birth in mesodermal tissues. We propose that the DMR1 region is a mesodermal silencer for Igf2, and that Igf2 imprinting is regulated by a combination of silencer and enhancer access. The DMR1 silencer may be regulated by allelic methylation.