Comparative methylomics reveals gene-body H3K36me3 in Drosophila predicts DNA methylation and CpG landscapes in other invertebrates

Here, we demonstrate that Nematostella vectensis, Ciona intestinalis, Apis mellifera, and B. mori, show two distinct populations of genes differentiated by gene-body CpG density. Genome-scale DNA methylation profiles for A. mellifera spermatozoa reveal CpG-poor genes are methylated in the germ line, as predicted by the depletion of CpGs. We find an evolutionarily conserved distinction between CpG-poor and -rich genes: the former are associated with basic biological processes, the latter with more specialized functions. This distinction is strikingly similar to that recently observed between euchromatin-associated genes in Drosophila that contain intragenic histone 3 lysine 36 trimethylation (H3K36me3) and those that do not, even though Drosophila doesnâ??t display CpG density bimodality or methylation. We confirm that a significant number of CpG-poor genes in N. vectensis, C. intestinalis, A. mellifera and B. mori are orthologs of H3K36me3- rich genes in Drosophila. We propose that over evolutionary time, gene-body H3K36me3 has influenced gene-body DNA methylation levels, and consequently the gene-body CpG density bimodality characteristic of invertebrates that harbor CpG methylation. Overall design: Examination of DNA methylation in Apis Mellifera sperm