DNA methylation patterns undergo genome-wide changes that occur immediately after fertilization and during early-preimplantation development. Alterations to DNA methylation also occur postnatally, with both gain and loss of CpG methylation during aging and disease. In addition to these intrinsic developmental and physiological functions, epigenetic regulation is thought to be a highly significant mechanism of how the genome interacts with the environment, interactions with potential major health implications.
It is widely accepted that environmental factors affect human behavior and disease. However, the relation to epigenetic changes has been elusive because methylation changes in non-cancer conditions are predicted to be non-clonal and stochastic, with one cell being differently affected than its neighbor. Such changes may be subtle and may be difficult, if not impossible, to convincingly detect by conventional methylation analyses. Our recently established DNA methylation reporter system represents a highly sensitive readout that may allow defining epigenetic changes in response to stress or abuse that may be apparent only at the single cell level.
The long-term goal of this project is to obtain mechanistic insights into DNA methylation and its role in (i) environmental–epigenome interactions and (ii) mammalian transgenerational epigenetic inheritance, both of which are relevant for human disease.