ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Nature 2017;547:419

Since the identification of DNA methylation as a master regulator of genomic imprinting more than 20 years ago, it has been the only known mammalian germline imprinting mark. However, recent studies have identified several imprinted genes capable of maintaining paternal allele-specific expression in the absence of oocyte DNA methylation. Here, the researchers find 76 genes that are paternally expressed (maternal alleles repressed) due to a DNA-methylation-independent mechanism. These genes are involved in and essential for embryonic development. A disease based on this new mechanism is Beckwith-Wiedemann syndrome of excess growth caused by mutation or deletion of imprinted genes within the chromosome 11p15.5 region, with disruption of the H19/IGF2-imprinting control region. The dynamics of non-DNA imprinting are strikingly different from DNA methylation-dependent imprinting that is largely maintained in both embryonic and extra-embryonic lineages. Non-DNA histone imprinting is probably established during oogenesis and maintained in preimplantation embryos, while it begins to dilute in the inner-cell mass of the blastocyst, and is almost completely lost in the epiblast of E6.5-9.5 embryos. A clinical consequence is that yet unexplained growth disorders might be revealed by future tests of histone methylation.