It remains unknown, however, how promoter DNA methylation changes throughout the MBT period, how it correlates with gene expression at the time of ZGA, and how it may contribute to pre-patterning developmental gene expression. Histone methylation may therefore cooperate with DNA methylation to shape tissue-specific gene expression. Genomic occupancy by trimethylated H3K4, H3K9 and H3K27 is initiated prior to ZGA and increases sharply thereafter. The pre-MBT and MBT periods are also characterized by increasing enrichment of the genome in post-translationally modified histones.

Shortly after the MBT stage, DNA methylation levels are similar to those of somatic tissues. Subsequent waves of transcriptional activation and inactivation control early development. Zebrafish embryos develop for ten cell cycles in the absence of transcription until the mid-blastula transition (MBT), at which time zygotic genome activation (ZGA) occurs. These observations suggest a view of maintenance of some sperm methylation patterns after fertilization and illustrate the diversity of methylation options in the embryo.ДЄs in mammals, zebrafish undergoes post-fertilization gametic demethylation and remethylation. Furthermore, Xenopus embryos retain a high methylation level after fertilization and show no correlation between promoter methylation and transcriptional repression. However, at least in the mouse, some non-imprinted genes retain parental promoter methylation and escape post-fertilization reprogramming, and over 1,000 methylated CpG islands (CGIs) are also incompletely demethylated even though they are not imprinted. The second occurs after fertilization, when maternal and paternal methylation patterns, except for imprinted genes, are erased and re-established during pre-implantation stages. The first occurs during germ cell development, when parental imprints are reset by demethylation and differential methylation of maternal and paternal alleles. The mammalian life cycle is marked by two waves of genome-wide DNA demethylation and remethylation.

In eukaryotes, DNA methylation occurs on cytosines in CpG dinucleotides and is stably inherited through cell division. DNA methylation is associated with long-term gene silencing and plays an important role in development, Г— chromosome inactivation and genomic imprinting. Lastly, although a significant proportion of genes methylated in sperm are unmethylated in embryos, over 90% of genes methylated in embryos are also methylated in sperm. Cohorts of genes differentially expressed through the MBT period display distinct promoter methylation patterns related to CG content rather than transcriptional fate.

H3K27me3 associates with either methylation state depending on its coincidence with H3K4me3 or H3K9me3. Hypomethylated regions constitute a platform for H3K4me3, whereas H3K9me3 preferentially associates with methylated regions. The MBT is marked by differential methylation of high and low CpG promoters, and we identify hypomethylated promoters that are mostly CG-rich and remain hypomethylated through the MBT. Results We show methylation of thousands of promoters before ZGA and additional methylation after ZGA, finding more dynamic methylation -1 to 0 kb upstream of the transcription start site than downstream. Using methylated DNA immunoprecipitation coupled to high-density microarray hybridization, we characterize genome-wide promoter DNA methylation dynamics before, during and after ZGA onset, in relation to changes in post-translational histone modifications and gene expression. Genome-scale gametic demethylation and remethylation occurs after fertilization, during blastula stages, but how ZGA relates to promoter DNA methylation states is unknown. Background Zygotic genome activation (ZGA) occurs at the mid-blastula transition (MBT) in zebrafish and is a period of extensive chromatin remodeling.

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