The occurrence of transgenerational epigenetic inheritance has overwhelming evidence in plants and invertebrates; however, the substantial erasure of DNA and histone modifications during early embryogenesis has been considered an insurmountable barrier to the transmission of epigenetic information in mammals. In a recent issue of Cell, Takahashi et al. demonstrate that engineered DNA methylation states of promoter-associated CpG islands can be inherited for multiple generations in mice.

DNA methylation and histone modifications are important regulators of chromatin organization, DNA replication and repair, transposon activity and gene expression. The deposition and removal of these modifications is a tightly regulated process that allows cell differentiation and adaptation to changing environments.¹ In invertebrates, plants and fungi, chromatin states were shown to be inherited independently of changes to the DNA sequence across multiple generations,² an example of what is known as “transgenerational epigenetic inheritance”.