Fig. 8: Putative novel enhancers overcome IGF2 imprinting in human hepatocytes.
From: Atlas of imprinted and allele-specific DNA methylation in the human body
A Allele-specific read counts for IGF2 (GTEx) show expression of either the A (X-axis) or B (Y-axis) alleles (blue dots). Conversely, mRNA from liver cells (red) show a diagonal, 1:1 allelic ratio, consistent with liver-specific escape of imprinting. B Known imprinting control mechanism for IGF2/H19. In the paternal allele (top), methylated CpGs (black lollipops) prevent CTCF from binding the iDMR, facilitating the activation of IGF2 by a distal enhancer. Conversely, in the maternal allele CTCF binds as the DMR is unmethylated, acting as an insulator66,68. We propose a mechanism by which liver-specific enhancers activate IGF2 in both maternal and paternal alleles, thus escaping maternal imprinting. C Genomic view of the H19/IGF2 locus. The putative liver enhancers (highlighted in blue) show strong H3K4me1 and H3K27ac ChIP-seq peaks in adult liver tissue (green and blue tracks), but not elsewhere. chromHMM adult liver (AL) track shows a putative annotation of this region as active enhancers (yellow). D Fragment-level analysis using our whole-genome methylation atlas shows fully unmethylated fragments (green) in six hepatocyte samples, at two adjacent putative enhancers (black frame), compared to fully methylated fragments in other cell types, where IGF2 is maternally imprinted.
