The fate of primordial germ cells
Primordial germ cells (PGCs) are the cells in the mammalian embryo that become gametes (sperm or eggs) in the adult organism. These cells are 'programmed' to become gametes through epigenetic changes, but the mechanisms of this change are not well understood. The EU-funded HISTONEGERMCELLS (The role of the histone variant H3.3 in epigenetic reprogramming of primordial germ cells) initiative aimed to understand the mechanisms that control these epigenetic changes in PGCs. They did this by studying histones, the proteins that DNA is wrapped around, allowing it to be packed tightly together when not in use. Specifically, HISTONEGERMCELLS focused on histone variant H3.3 and the histone chaperone protein HIRA, which controls histone activity. Previous research has shown that H3.3 has an important role in PGC reprogramming. Researchers studied specially bred mice to understand how these two proteins influence PGCs. Most importantly, they found that H3.3 is mainly incorporated into the DNA-histone bundle (called a nucleosome) near regulatory elements called enhancers. This allows genes within that nucleosome to be transcribed into proteins – presumably triggering the changes seen in PGCs. Researchers then mapped all these enhancer regions, which are inactive in precursor cells but activated by H3.3 to induce development of PGCs. The findings of HISTONEGERMCELLS contribute to our understanding of embryonic development and could have applications for disease prevention in the future.
