Article

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: 13.85). 09/2011; 21(11):1841-50. DOI: 10.1101/gr.121640.111
Source: PubMed

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.

1 Follower
 · 
110 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The network of NF-κB-dependent transcription that activates both pro- and anti-inflammatory genes in mammals is still unclear. As NF-κB factors are evolutionarily conserved, we used Drosophila to understand this network. The NF-κB transcription factor Relish activates effector gene expression following Gram-negative bacterial immune challenge. Here, we show, using a genome-wide approach, that the conserved nuclear protein Akirin is a NF-κB co-factor required for the activation of a subset of Relish-dependent genes correlating with the presence of H3K4ac epigenetic marks. A large-scale unbiased proteomic analysis revealed that Akirin orchestrates NF-κB transcriptional selectivity through the recruitment of the Osa-containing-SWI/SNF-like Brahma complex (BAP). Immune challenge in Drosophila shows that Akirin is required for the transcription of a subset of effector genes, but dispensable for the transcription of genes that are negative regulators of the innate immune response. Therefore, Akirins act as molecular selectors specifying the choice between subsets of NF-κB target genes. The discovery of this mechanism, conserved in mammals, paves the way for the establishment of more specific and less toxic anti-inflammatory drugs targeting pro-inflammatory genes.
    The EMBO Journal 08/2014; DOI:10.15252/embj.201488456 · 10.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Epigenetics is known to be involved in recombination initiation, but the effects of specific epigenetic marks like DNA methylation on recombination are relatively unknown. Studies in Arabidopsis and the fungus Ascobolus immersus suggest that DNA methylation may suppress recombination rates and/or alter its distribution across the genome, however, these patterns appear complex, and more direct inquiries are needed. Unlike other organisms, Drosophila only have one known DNA methyltransferase, DNMT2, which is expressed in the ovaries and historically has been thought to be responsible for limited genomic DNA methylation. To test for a role of DNMT2 on the frequency and distribution of recombination, I compared recombination rates between Dnmt2 -/- and Dnmt2 +/- Drosophila melanogaster individuals in two euchromatic regions and one heterochromatic region across the genome. I failed to detect an altered pattern of recombination rate in the absence of DNMT2 in all regions surveyed, and conclude that other epigenetic effects are regulating recombination initiation in Drosophila.
    G3-Genes Genomes Genetics 08/2014; DOI:10.1534/g3.114.012393 · 2.51 Impact Factor
  • Source
    [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 · 3.00 Impact Factor

Preview

Download
1 Download
Available from