Retention of paternal DNA methylome in the developing zebrafish germline

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.

Immune genes, IL1β and Casp9, show sexual dimorphic methylation patterns in zebrafish gonads

“…Epigenetic changes (or epimutations) can be inherited cell to cell through mitotic divisions or throughout subsequent generations by meiotic divisions (Dupont et al, 2009;Hanson and Skinner, 2016). Inheritable epimutations need to occur in the primordial germ cells (PGCs) during embryo formation, which in humans occurs over the first 6-18 weeks of gestation (Jirtle and Skinner, 2007) and in zebrafish (Danio rerio), PGCs were already observed four hours post fertilization (4 hpf, blastula stages) (Skvortsova et al, 2019). In addition, gametogenesis in the gonads, i.e.…”

The round goby genome provides insights into mechanisms that may facilitate biological invasions

“…For example, non-methylated genome regions in fish are unexpectedly CG-poor [142], fish differ from mammals with respect to the distribution of methylated CpGs in the genome [143], algorithms developed on mammals fail to identify CpG islands in fish [144], genome-wide CpG island predictions in cold-blooded animals consist primarily of false positives [145], and fish CG methylation occurs mainly in coding regions, where it correlates positively with gene expression levels [146]. DNA methylation dynamics in the germline follows distinct and non-mammalian patterns in zebrafish [147,148], mangrove fish [149], and medaka [150], and copy number variations in the de novo DNA methyltransferase DNMT3 in teleosts do not reflect teleost genome duplication events [116]. Together with distinct spatiotemporal expression patterns particularly during development [151][152][153][154], the peculiarities of the fish DNA methylation machinery clearly warrant an in-depth and species-aware exploration of the role of DNA methylation in fish.…”

Pervasive non-CpG methylation at zebrafish mosaic satellite repeats

“…Egg (GSM1133392), sperm (GSM1133391), 32cell (GSM1133394), 64cell (GSM1133395) and germring (GSM1133398) (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE44075) [21]. 4hpf (GSM3484060, GSM3484068), 7hpf (GSM3484061, GSM3484069) and liver (GSM3505059) (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE122722) [24]. ChIP seq datasets analysed in this study were taken from the following GEO records: H3K9me3 at 6hpf (GSM3096185, GSM3096186), 4.5hpf (GSM3096189, GSM3096190) and 2.5hpf (GSM3096193, GSM3096194) (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE113086) [35].…”

“…They exhibit expression in a diverse range of tissues many of which are neural by origin, however, their expression is not exclusively limited to the nervous system [18] (Additional File 1: Figure S4). Numerous reports have previously described the developmental dynamics of zebrafish CG methylation in somatic and germline tissues [12,[19][20][21][22][23][24][25][26][27]. To further investigate the developmental dynamics of mCH, we reanalyzed base-resolution profiles of liver, sperm, egg, 32 cell stage, 64 cell stage, sphere, germring, and shield embryos [21,24] (Additional File 1: Table S2).…”

“…Numerous reports have previously described the developmental dynamics of zebrafish CG methylation in somatic and germline tissues [12,[19][20][21][22][23][24][25][26][27]. To further investigate the developmental dynamics of mCH, we reanalyzed base-resolution profiles of liver, sperm, egg, 32 cell stage, 64 cell stage, sphere, germring, and shield embryos [21,24] (Additional File 1: Table S2). mCH levels of MOSAT motifs in commonly covered MOSAT_DR elements (8064 sites from 3091 elements) revealed high mCH levels in adult germ cells, cleavage stage embryos and late stage embryos/adult tissues but low levels surrounding the sphere stage, which corresponds to the major wave of zygotic genome activation-ZGA ( Fig.…”