Proposal Summary/Abstract
During mouse embryonic development, approximately 40 cells in the post-implantation epiblast are
designated as Primordial Germ Cells (PGCs) and destined to become sperm or egg. PGCs undergo global
epigenetic remodeling, which is not seen in the surrounding somatic cells. The repressive histone modification
H3K9me2 is depleted during PGC specification. In parallel, DNA is demethylated in two waves: a global erasure
followed by a loci specific depletion. The only locations to escape this first wave of global erasure are a few germ
cell specifying genes, imprinted loci, and transposable elements. How these loci are protected from the first
phase of DNA demethylation is still unknown. Previous data from my thesis lab has shown that in somatic cell
reprogramming to induced pluripotent stem cells, there is coordinated removal of the same repressive epigenetic
marks of H3K9me2 and DNA methylation. I propose that H3K9me2 demethylases KDM3A and KDM3B have
important roles in PGC development which I will investigate using an in vitro PGC-like cell differentiation model
and Next-generation sequencing experiments. This research will elucidate the importance of removal of
repressive modifications to prevent transgenerational epigenetic inheritance which could be disruptive to
embryonic development, germ cell specification, and fertility.