UC Santa Barbara

Gene body methylation (GBM) is an ancestral mode of DNA methylation whose role in development has been obscured by the more prominent roles of promoter and CpG island methylation. The wasp Nasonia vitripennis has little promoter and CpG island methylation, yet retains strong GBM, making it an excellent model for elucidating the roles of GBM. Here we show that N. vitripennis DNA methyltransferase 1a (Nv-Dnmt1a) knockdown leads to failures in cellularization and gastrulation of the embryo. Both of these disrupted events are hallmarks of the maternal-zygotic transition (MZT) in insects. Analysis of the embryonic transcriptome and methylome revealed strong reduction of GBM and widespread disruption of gene expression during embryogenesis after Nv-Dnmt1a knockdown. Strikingly, there was a strong correlation between loss of GBM and reduced gene expression in thousands of methylated loci, consistent with the hypothesis that GBM directly facilitates high levels of transcription. We propose that lower expression levels of methylated genes due to reduced GBM is the crucial direct effect of Nv-Dnmt1 knockdown. Subsequently, the disruption of methylated genes leads to downstream dysregulation of the MZT, culminating in developmental failure at gastrulation.