title: Comparative methylomics reveals gene-body H3K36me3 in Drosophila predicts DNA methylation and CpG landscapes in other invertebrates.
abstract: In invertebrates that harbor functional DNA methylation enzymatic machinery, gene-bodies are the primary targets for CpG methylation. However, virtually all other aspects of invertebrate DNA methylation have remained a mystery until now. Here, using a comparative methylomics approach, we demonstrate that Nematostella vectensis, Ciona intestinalis, Apis mellifera, and Bombyx 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 germline, as predicted by the depletion of CpGs. We find an evolutionarily conserved distinction between CpG-poor and GpC-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 does not 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.
authors.affiliation: The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, United Kingdom.
authors.forename: Lisa
authors.initials: L
authors.lastname: Nanty
authors.forename: Guillermo
authors.initials: G
authors.lastname: Carbajosa
authors.forename: Graham A
authors.initials: GA
authors.lastname: Heap
authors.forename: Francis
authors.initials: F
authors.lastname: Ratnieks
authors.forename: David A
authors.initials: DA
authors.lastname: van Heel
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Down
authors.forename: Vardhman K
authors.initials: VK
authors.lastname: Rakyan
mesh_terms: D000818:Animals; D018899:CpG Islands; D019175:DNA Methylation; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D005091:Exons; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007448:Invertebrates / Q000235:genetics / Q000378:metabolism; D008745:Methylation
chemical_list: D006657:Histones