FIGURE 3.

Epigenetic regulation of the imprinted IGF2-H19 gene cluster. The regulation of the imprinted genes is mediated by imprinting control regions (ICR) whose methylation regulates the imprinted genes located at the same gene cluster. On the maternal allele, at the IGF2-H19 locus, the ICR is de-methylated; this allows CTCF binding and promotes the expression of H19 and silencing of IGF2 through down-stream enhancer activity. On the paternal allele, at the IGF2-H19 locus, the ICR and H19 are methylated; this prevents CTCF binding and induces the inactivation of H19 and the expression of IGF2. Consistently, IGF2 is expressed in the sperm cell (Cannarella et al., 2019).