Transgenerational inheritance of epigenetic instability and developmental phenotypes
"Exposure to environmental stressors, such as poor nutrition, can affect an individual's epigenome and increase their risk of disease over the course of their lifetime. Whether changes in the epigenome can be inherited by the next generation via escaping epigenetic reprogramming is widely speculative as the mechanism is not well understood. In the lab, we work on a mouse model of abnormal folate metabolism that results in epigenetic instability. Remarkably, this epigenetic instability is inherited between generations since wildtype grandprogeny (F2) derived from maternal grandparents with abnormal folate metabolism have global DNA hypomethylation and widespread locus-specific dysregulation of DNA methylation that is associated with gene misexpression and developmental phenotypes. Our goal in the lab is to use this mouse model to tease apart the molecular mechanisms of transgenerational inheritance, which is clearly complex."