Epigenetic reprogramming in mouse and human primordial germ cells

Primordial germ cells (PGCs) are the precursors of sperm and eggs. They undergo genome-wide epigenetic reprogramming to erase epigenetic memory and reset the genomic potential for totipotency. Global DNA methylation erasure is a crucial part of epigenetic resetting when DNA methylation levels decrease across the genome to <5%. However, certain localized regions exhibit slower demethylation or resistance to reprogramming. Since DNA methylation plays a crucial role in transcriptional regulation, this depletion in PGCs requires mechanisms independent of DNA methylation to regulate transcriptional control during PGC reprogramming. Histone modifications are predicted to compensate for the loss of DNA methylation in gene regulation. Different histone modifications exhibit distinct patterns in PGCs undergoing epigenetic programming at the genomic level during PGC development in conjunction with changes in DNA methylation. Together, they contribute to PGC-specific genomic regulation. Recent findings related to these processes provide a comprehensive overview of germline epigenetic reprogramming and its importance in mouse and human PGC development. Additionally, we evaluated the extent to which in vitro culture techniques have replicated the development processes of human PGCs. Primordial germ cells (PGCs), which eventually become eggs or sperm, undergo unique and important changes early in their development that are crucial for forming a complete organism after fertilization. Recent studies have advanced our understanding of these changes. This review explains how certain processes, such as adding chemical markers to DNA (DNA methylation) and modifying proteins around DNA (histone modifications), control the development of PGCs in humans and mice. It also explores the replication of these processes in the lab using human stem cells. This review provides important insights into the impact of these changes on reproduction and offers potential new avenues for treating infertility. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.