The dynamic chromatin landscape and mechanisms of DNA methylation during mouse germ cell development.

Epigenetic marks including DNA methylation (DNAme) play a critical role in the transcriptional regulation of genes and retrotransposons. Defects in DNAme are detected in infertility, imprinting disorders and congenital diseases in humans, highlighting the broad importance of this epigenetic mark in both development and disease. While DNAme in terminally differentiated cells is stably propagated following cell division by the maintenance DNAme machinery, widespread erasure and subsequent de novo establishment of this epigenetic mark occur early in embryonic development as well as in germ cell development. Combined with deep sequencing, low-input methods that have been developed in the past several years have enabled high-resolution and genome-wide mapping of both DNAme and histone post-translational modifications (PTMs) in rare cell populations including developing germ cells. Epigenome studies using these novel methods reveal an unprecedented view of the dynamic chromatin landscape during germ cell development. Furthermore, integrative analysis of chromatin marks in normal germ cells and in those deficient in chromatin-modifying enzymes uncovers a critical interplay between histone PTMs and de novo DNAme in the germline. This review discusses work on mechanisms of the erasure and subsequent de novo DNAme in mouse germ cells as well as the outstanding questions relating to the regulation of the dynamic chromatin landscape in germ cells.