Developmental features of DNA methylation during activation of the embryonic zebrafish genome

Abstract

BackgroundZygotic genome activation (ZGA) occurs at the mid-blastula transition (MBT) in zebrafish and is a period of extensive chromatin remodeling. Genome-scale gametic demethylation and remethylation occurs after fertilization, during blastula stages, but how ZGA relates to promoter DNA methylation states is unknown. 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.ResultsWe 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. 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. Hypomethylated regions constitute a platform for H3K4me3, whereas H3K9me3 preferentially associates with methylated regions. H3K27me3 associates with either methylation state depending on its coincidence with H3K4me3 or H3K9me3. Cohorts of genes differentially expressed through the MBT period display distinct promoter methylation patterns related to CG content rather than transcriptional fate. 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.ConclusionsOur results suggest a pre-patterning of developmental gene expression potential by a combination of DNA hypomethylation and H3K4 trimethylation on CG-rich promoters, and are consistent with a transmission of DNA methylation states from gametes to early embryos.

Zygotic Genome Activation During the Maternal-to-Zygotic Transition

“…Repressive interactions with methyl-CpG-binding domain proteins such as Xenopus Kaiso are necessary to regulate transcriptional timing at ZGA (Ruzov et al, 2004). Conversely, DNA hypomethylation is generally predictive of genes expressed at ZGA (Potok et al, 2013; Stancheva et al, 2002) and the deposition of H3K4me3 marks (Andersen et al, 2012), though again in Xenopus the relationship between methylation and gene expression may be more complex (Bogdanovic et al, 2011). …”

Functional DNA methylation differences between tissues, cell types, and across individuals discovered using the M&M algorithm

“…DNA methylation has been investigated for its role in specifying tissue-specific gene expression (Song et al 2005;Shen et al 2007;Irizarry et al 2009;Laurent et al 2010;Maunakea et al 2010;Liang et al 2011;Andersen et al 2012;Davies et al 2012). It has long been appreciated that DNA methylation of non-CpG island gene promoters is a durable mechanism that results in repression of genes in specific tissues during development (Lamson and Stockdale 1989;Luo et al 2000;Winders et al 2004).…”

Glucose overload in yolk has little effects on the long term modulation of carbohydrate metabolic genes in zebrafish (Danio rerio)

“…temperature) can lead to genomic imprinting in fish, through changes in DNA methylation (Campos et al, 2013;Navarro-Martín et al, 2011). Moreover, important elements associated with epigenetic mechanisms have been recently reported in zebrafish (Andersen et al, 2012).…”