Question

During specification of primordial germ cells, what kinds of genome-wide epigenetic re-programmings primordial germ cells undergo?

Answer 1

Epigenetic events during mammalian germ cell development.

• The epigenetic modifiers have key roles in genome-wide reprogramming and activation and repression of specific genes during mammalian germ-cell development.

• Germ-cell specification and suppression of the somatic gene expression programme might involve epigenetic modifications. Furthermore, differentiating primordial germ cells (PGCs) show global reduction in repressive epigenetic marks, and activation and repression of post-migratory PGC-specific genes involves DNA methylation and histone-arginine methylation.

• In post-migratory PGCs, epigenetic imprints that are specific to the parent of origin are erased. Subsequently, sex-specific imprints are established during male and female gametogenesis, and the de novo DNA methylation machinery has a central role in this process.

• DNA methylation is important for silencing retrotransposons in germ cells and therefore contributes to the maintenance of genomic integrity. Recent studies have revealed a link between DNA methylation and small-RNA-mediated silencing mechanisms.

• A number of histone methyltransferases are essential for establishing a chromosome structure that is appropriate for events that occur during meiosis and for activation and repression of genes that are necessary or unnecessary for meiosis. Meiotic sex-chromosome inactivation in male germ cells involves histone variants and epigenetic modifications.

• Global nuclear remodelling including histone–protamine exchange occurs in haploid spermatids. Expression of some haploid-specific genes relies on histone demethylation.

• A better understanding of the epigenetic regulation of germ-cell development will be of great importance for improvement of reproductive engineering technologies and human health.