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

The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, United Kingdom.
Genome Research (Impact Factor: 14.63). 09/2011; 21(11):1841-50. DOI: 10.1101/gr.121640.111
Source: PubMed


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.

Download full-text


Available from: Graham A Heap, Oct 06, 2015
  • Source
    • "Less is known about the role of histone PTMs in other insects. However, Nanty and colleagues showed that patterns of histone PTMs are largely conserved between invertebrate species and can therefore be predicted for different taxa (Nanty et al., 2011). Indeed, DNA methylation and histone modifications seem to work together, if not "
    [Show abstract] [Hide abstract]
    ABSTRACT: Insects are one of the most successful classes on Earth, reflected in an enormous species richness and diversity. Arguably, this success is partly due to the high degree to which polyphenism, where one genotype gives rise to more than one phenotype, is exploited by many of its species. In social insects, for instance, larval diet influences the development into distinct castes; and locust polyphenism has tricked researchers for years into believing that the drastically different solitarious and gregarious phases might be different species. Solitarious locusts behave much as common grasshoppers. However, they are notorious for forming vast, devastating swarms upon crowding. These gregarious animals are shorter lived, less fecund and transmit their phase characteristics to their offspring. The behavioural gregarisation occurs within hours, yet the full display of gregarious characters takes several generations, as does the reversal to the solitarious phase. Hormones, neuropeptides and neurotransmitters influence some of the phase traits; however, none of the suggested mechanisms can account for all the observed differences, notably imprinting effects on longevity and fecundity. This is why, more recently, epigenetics has caught the interest of the polyphenism field. Accumulating evidence points towards a role for epigenetic regulation in locust phase polyphenism. This is corroborated in the economically important locust species Locusta migratoria and Schistocerca gregaria. Here, we review the key elements involved in phase transition in locusts and possible epigenetic regulation. We discuss the relative role of DNA methylation, histone modification and small RNA molecules, and suggest future research directions. © 2015. Published by The Company of Biologists Ltd.
    Journal of Experimental Biology 01/2015; 218(Pt 1):88-99. DOI:10.1242/jeb.107078 · 2.90 Impact Factor
  • Source
    • "In the genes examined, the proportion showing methylation and low CpG content was 10-fold higher than the proportion of methylated genes with a high CpG content (Nanty et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: In honey bees (Apis mellifera), the epigenetic mark of DNA methylation is central to the developmental regulation of caste differentiation, but may also be involved in additional biological functions. In this study, we examine the whole genome methylation profiles of three stages of the haploid honey bee genome: unfertilised eggs, the adult drones that develop from these eggs and the sperm produced by these drones. These methylomes reveal distinct patterns of methylation. Eggs and sperm show 381 genes with significantly different CpG methylation patterns, with the vast majority being more methylated in eggs. Adult drones show greatly reduced levels of methylation across the genome when compared with both gamete samples. This suggests a dynamic cycle of methylation loss and gain through the development of the drone and during spermatogenesis. Although fluxes in methylation during embryogenesis may account for some of the differentially methylated sites, the distinct methylation patterns at some genes suggest parent-specific epigenetic marking in the gametes. Extensive germ line methylation of some genes possibly explains the lower-than-expected frequency of CpG sites in these genes. We discuss the potential developmental and evolutionary implications of methylation in eggs and sperm in this eusocial insect species.
    Development 06/2014; 141(13):2702-11. DOI:10.1242/dev.110163 · 6.46 Impact Factor
  • Source
    • "DNA methylation involves the modification of a DNA base, most often a cytosine in a CpG dinucleotide pair, with the addition of a methyl group thus affecting the coiling of DNA around histones and changing the potential binding of transcriptional factors in part by recruiting methyl CpG binding proteins (MCBPs). Although absolute levels of DNA methylation vary between species and cell types (Lister et al., 2009; Feng et al., 2010a; Zemach et al., 2010; Nanty et al., 2011), in humans there is experimental evidence for 80–96% of the CpG residues in the genome being methylated under various conditions (Varley et al., 2013; Ziller et al., 2013). Much of our understanding of the function of DNA methylation has come from imprinting in mammals (reviewed in Abramowitz and Bartolomei, 2012) and the study of cancer cell lines (reviewed in Laird and Jaenisch, '96), where DNA methylation is often aberrant, both in placement, and in pattern (Miremadi et al., 2007; Cedar and Bergman, 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Epigenetic mechanisms are proposed as an important way in which the genome responds to the environment. Epigenetic marks, including DNA methylation and Histone modifications, can be triggered by environmental effects, and lead to permanent changes in gene expression, affecting the phenotype of an organism. Epigenetic mechanisms have been proposed as key in plasticity, allowing environmental exposure to shape future gene expression. While we are beginning to understand how these mechanisms have roles in human biology and disease, we have little understanding of their roles and impacts on ecology and evolution. In this review, we discuss different types of epigenetic marks, their roles in gene expression and plasticity, methods for assaying epigenetic changes, and point out the future advances we require to understand fully the impact of this field. J. Exp. Zool. (Mol. Dev. Evol.) 9999B: 1–13, 2014. © 2014 Wiley Periodicals, Inc.
    Journal of Experimental Zoology Part B Molecular and Developmental Evolution 06/2014; 322(4). DOI:10.1002/jez.b.22571 · 2.31 Impact Factor
Show more