Sperm, but Not Oocyte, DNA Methylome Is Inherited by Zebrafish Early Embryos

Abstract

SUMMARY 5-methylcytosine is a major epigenetic modification that is sometimes called “the fifth nucleotide.” However, our knowledge of how offspring inherit the DNA methylome from parents is limited. We generated nine single-base resolution DNA methylomes, including zebrafish gametes and early embryos. The oocyte methylome is significantly hypomethylated compared to sperm. Strikingly, the paternal DNA methylation pattern is maintained throughout early embryogenesis. The maternal DNA methylation pattern is maintained until the 16-cell stage. Then, the oocyte methylome is gradually discarded through cell division and is progressively reprogrammed to a pattern similar to that of the sperm methylome. The passive demethylation rate and the de novo methylation rate are similar in the maternal DNA. By the midblastula stage, the embryo’s methylome is virtually identical to the sperm methylome. Moreover, inheritance of the sperm methylome facilitates the epigenetic regulation of embryogenesis. Therefore, besides DNA sequences, sperm DNA methylome is also inherited in zebrafish early embryos.

Transcriptional Activity and DNA Methylation Dynamics of the Gal4/UAS System in Zebrafish

“…The epigenetic states of sperm and oocytes are highly asymmetric in mice (Cedar and Bergman 2012) and zebrafish (Mhanni and McGowan 2004). Recently, two independent studies of zebrafish genome-wide DNA methylation profiles revealed that the paternal methylomes are stably inherited without significant changes from fertilization into the sphere stage; by contrast, maternal methylomes are reprogrammed such that their epigenetic states match the paternal methylomes after fertilization (Potok et al 2013;Jiang et al 2013). These findings suggest that the paternal DNA and maternal DNA undergo different dynamic changes.…”

“…5b). Recent research studying methylation in early zebrafish development using whole-genome bisulfite sequencing has revealed a cluster of differentially methylated regions (DMRs) that are hypermethylated in the egg, hypomethylated in the sperm, moderately methylated from the 2-cell to 256-cell stage, and hypomethylated at the sphere stage (Potok et al 2013;Jiang et al 2013). This cluster of loci has a relatively high CpG obs/exp ratio (~1.10) which is close to the obs/exp ratio (0.97) of the 4xUAS in our study.…”

“…However, in our study, the paternal 4xUAS underwent both rapid de novo methylation and demethylation, which differs from the results of previous whole-genome methylation profile analyses. In those studies, the methylation statuses of 22 DMRs between the paternal and maternal loci were analyzed only in 8-cell stage embryos (Jiang et al 2013) or in a mixture of 2-to 16-cell stage embryos (Potok et al 2013).…”

Paternal contribution to development: Sperm genetic damage and repair in fish

“…After fertilization, sperm DNA is quickly demethylated in mammals except in some specific loci (O'Doherty and McGettigan 2014;Miller et al 2010;Okada et al 2010) which are supposed to be necessary for a proper progress in early embryogenesis. However in zebrafish, whose sperm chromatin, as was explained before, is fully compacted with histones (Wu et al 2011), DNA reprogramming after fertilization follows a different mechanism, early embryos inheriting sperm DNA methylome (Jiang et al 2013). Maintenance of a proper methylation at specific gene promoters is required for an appropriate sperm function and aberrant methylation patterns have been associated with infertility and poor sperm quality in men (Jenkins and Carrell 2012b;Jenkins and Carrell 2012a;Houshdaran et al 2007).…”

Lessons from zebrafish on reprogramming the epigenetic code after fertilisation

“…Remarkably, the methylation status of the maternally-derived genome was reset to the male pattern as one unit. 3 Of the large number of loci that were differentially methylated in the sperm and oocyte, most were resolved to the spermspecific pattern by gastrulation. Many of the loci that were differentially methylated encoded genes known to be involved in early embryogenesis, so this provides some reassurance that these reprogramming events are developmentally relevant.…”