Evolutionary conservation of embryonic DNA methylome remodelling in distantly related teleost species

Abstract

Methylation of cytosines in the CG context (mCG) is the most abundant DNA modification in vertebrates that plays crucial roles in cellular differentiation and identity. After fertilization, DNA methylation patterns inherited from parental gametes are remodelled into a state compatible with embryogenesis. In mammals, this is achieved through the global erasure and re-establishment of DNA methylation patterns. However, in non-mammalian vertebrates like zebrafish, no global erasure has been observed. To investigate the evolutionary conservation and divergence of DNA methylation remodelling in teleosts, we generated base resolution DNA methylome datasets of developing medaka and medaka-zebrafish hybrid embryos. In contrast to previous reports, we show that medaka display comparable DNA methylome dynamics to zebrafish with high gametic mCG levels (sperm: ∼90%; egg: ∼75%), and adoption of a paternal-like methylome during early embryogenesis, with no signs of prior DNA methylation erasure. We also demonstrate that non-canonical DNA methylation (mCH) reprogramming at TGCT tandem repeats is a conserved feature of teleost embryogenesis. Lastly, we find remarkable evolutionary conservation of DNA methylation remodelling patterns in medaka-zebrafish hybrids, indicative of compatible DNA methylation maintenance machinery in far-related teleost species. Overall, these results suggest strong evolutionary conservation of DNA methylation remodelling pathways in teleosts, which is distinct from the global DNA methylome erasure and reestablishment observed in mammals.

Extensive DNA methylome rearrangement during early lamprey embryogenesis

“…3I ). Overall, we found the greatest number of overlaps between egg/sperm, egg/day 1 and egg/day 2 DMRs, suggestive of maternal-to-paternal DMR reprogramming, as previously described in zebrafish and medaka 10 , 26 – 29 . Next, we merged all DMRs into a single dataset and performed clustering of mCG levels (Fig.…”

“…S4H ). Nevertheless, it is worth pointing out that relationships between promoter mCG and transcriptional silencing are complex 55 , 61 , 62 and that even in organisms with highly methylated genomes, like zebrafish and medaka 10 , 26 , 27 , 29 , such clear anti-correlation can only be observed on a small number of genes. Altogether, our results indicate discrete mCG remodeling occurring not only within, but also alongside large-scale genomic transitions in PMD state during early development, affecting at least 2% of the genome.…”

“…We demonstrate that mCG patterns in the early embryo closely resemble sperm, thereby reflecting a maternal-to-paternal epigenome transition event upon fertilization. Lamprey exhibits developmental mCG dynamics similar to zebrafish and medaka, thus providing valuable insights into the evolutionary origins of vertebrate mCG reprogramming 10 , 25 – 27 , 29 (Fig. 5 ).…”

“…Thus, mCG patterns in the early embryo closely resemble those of sperm. Moreover, we have recently identified maternal-to-paternal DNA methylome remodeling in medaka embryos, revealing evolutionary conservation of developmental epigenome dynamics in distantly related teleost species 29 .…”

The chromatin accessibility dynamics during cell fate specifications in zebrafish early embryogenesis

“…In addition, several motifs were identified as specifically enriched in peaks from module 10. When the DNA methylation profiles were examined around these LTRs within module 10 at 3 hpf (1k stage) from a recent study (56), they were quite different from DNA methylation profiles of typical open chromatin regions (Supplementary Figure 3E). Therefore, the exact meaning and functional implications of reduced chromatin accessibility of LTRs in module 10 during development need further investigation.…”