Epigenetics
Genomic imprinting is surmised to have arisen due to the conflicting interests of maternal and paternal genes within a pregnancy.
Within a pregnancy, the father wants the mother to devote as much of her resources as possible towards the growth (benefit) of his offspring. However, within the same pregnancy, the mother wants to conserve as much of her resources as possible towards future births without compromising the health of the child(ren) she is currently carrying.
H19 contains a differentially methylated region that is also an imprinting control region. This imprinting control region is differentially methylated at its CpGs according to parental inheritance. Usually, the paternal copy of H19 is methylated and silent while the maternal copy is hypomethylated or unmethylated and expressed in the offspring cell. Methylation of the H19 promoter is negatively correlated with H19 expression.
As methylation of the promoter reaches 100%, H19 expression from that promoter approaches 0. At the same time as H19 expression decreases, the expression of IGF2, a neighboring gene on chromosome 11, increases.
Cells treated with Azad, a demethylating agent, grow much slower than cells cultured in the absence of Azad. At the same time, H19 expression increases while IGF2 expression decreases in the presence of Azad. The reduction of IGF2 expression could be a reason for the slower growth of cells treated with Azad. As well, in a mouse bladder carcinoma cell line, where transfection of a human H19 DNA construct results in high expression of H19, the methylation of the H19 promoter reduces H19 expression. The paternal H19 allele, which is silent postnatally, shows increasing methylation of CpGs in its promoter with gestation time in the fetus. It appears conclusive that the H19 gene is epigenetically controlled via methylation, where methylation on or near the vicinity of one allele prevents the expression of that allele. As well, based on the results from Banet et al., it appears that functional H19 imprinting occurs during early placenta development.
Read more about this topic: H19 (gene)