Abstract
Two waves of DNA methylation reprogramming occur during mammalian embryogenesis; during preimplantation development and during primordial germ cell (PGC) formation. However, it is currently unclear how evolutionarily conserved these processes are. Here we characterise the DNA methylomes of zebrafish PGCs at four developmental stages and identify retention of paternal epigenetic memory, in stark contrast to the findings in mammals. Gene expression profiling of zebrafish PGCs at the same developmental stages revealed that the embryonic germline is defined by a small number of markers that display strong developmental stage-specificity and that are independent of DNA methylation-mediated regulation. We identified promoters that are specifically targeted by DNA methylation in somatic and germline tissues during vertebrate embryogenesis and that are frequently misregulated in human cancers. Together, these detailed methylome and transcriptome maps of the zebrafish germline provide insight into vertebrate DNA methylation reprogramming and enhance our understanding of the relationships between germline fate acquisition and oncogenesis.
Highlights
Two waves of DNA methylation reprogramming occur during mammalian embryogenesis; during preimplantation development and during primordial germ cell (PGC) formation
Absence of genome-wide 5mC reprogramming in zebrafish PGCs
To further assess the purity level of sorted PGC populations, we examined the expression of known germline markers
Summary
Two waves of DNA methylation reprogramming occur during mammalian embryogenesis; during preimplantation development and during primordial germ cell (PGC) formation. It is currently unclear how evolutionarily conserved these processes are. Vertebrate embryogenesis requires tight orchestration of spatiotemporal gene expression patterns This is achieved through the coordinated action of transcription factors, diverse signalling molecules and genomic regulatory marks such as DNA methylation (5-methylcytosine; 5mC) and histone tail modifications[1]. The acquisition of these regulatory determinants defines key developmental stages and is implicated in processes such as pluripotency establishment and cell differentiation. DNA demethylation, which due to its dynamics can not be fully explained by passive 5mC dilution[17]
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