Laboratory for Epigenome Inheritance

Genetic information is passed on to the offspring through oocytes and sperms (gametes) and greatly contributes to their phenotypes and disease susceptibility. Recent studies have revealed that the parental genomes are accompanied by epigenetic information that is also passed on to the next generation. Defects in epigenetic inheritance lead to various phenotypes in prenatal and postnatal growth in mice. This raises the possibility that epigenetic changes in gametes, possibly induced by the parental environment, might influence disease susceptibility in the offspring via an epigenetic inheritance cascade.

Our laboratory is studying the mechanisms and functions of intergenerational inheritance of histone post-translational modifications (hPTMs) in mammals. Our specific aims are as follows (Figure): (1) To understand the molecular basis and functions of hPTM establishment and inheritance during gametogenesis and early embryogenesis. (2) To link hPTM inheritance to the pre- and peri-conceptional parental environment; (3) To understand how the parental environment might influence disease susceptibility in the offspring. To address these questions, we integrate cutting-edge low-input epigenomic technologies, reproductive engineering techniques, and various genome/epigenome-modified mouse models. This study will not only reveal how parental lifestyle influences epigenetic memory and gene expression in germ cells but will also call for an evaluation of the contribution of epigenetic mechanisms to hereditary diseases. It will provide a basis for new approaches to preventive and predictive medicine.