The Szabó Laboratory studies the molecular mechanisms responsible for resetting the epigenome between generations in general and specifically in the context of genomic imprinting.
Both the soma-germline and the germline-soma transitions involve global erasure and reestablishment of DNA methylation patterns. At the soma-germline transition, the paternally and maternally inherited sets of chromosomes are prepared separately in the male and in the female germlines. The chromosomes in the sperm and egg contribute to the next generation when they join at fertilization. Soon after fertilization––at the germline-soma transition––the two half genomes undergo another wave of global remodeling initiating somatic development. The chromosomes inherited from the sperm or the egg carry with them into the soma an epigenetic memory of the male or female germlines, which is detectable in the parental-allele-specific transcription of imprinted genes.
The Szabó Laboratory is interested in the mechanisms of how DNA methylation is erased in primordial germ cells and in the zygote. We also study the patterning of de novo DNA methylation in fetal male germ cells. We use the tools of molecular biology and mouse genetics to map the changes in the epigenome and identify the specific molecules that take part in these global and imprinted locus-specific processes. In addition, we test whether the natural epigenetic reprogramming processes of the germline are sensitive to environmental insults, potentially leading to transgenerational epigenetic inheritance.