Abstract

BackgroundTransposition is disruptive in nature and, thus, it is imperative for host genomes to evolve mechanisms that suppress the activity of transposable elements (TEs). At the same time, transposition also provides diverse sequences that can be exapted by host genomes as functional elements. These notions form the basis of two competing hypotheses pertaining to the role of epigenetic modifications of TEs in eukaryotic genomes: the genome defense hypothesis and the exaptation hypothesis. To date, all available evidence points to the genome defense hypothesis as the best explanation for the biological role of TE epigenetic modifications.ResultsWe evaluated several predictions generated by the genome defense hypothesis versus the exaptation hypothesis using recently characterized epigenetic histone modification data for the human genome. To this end, we mapped chromatin immunoprecipitation sequence tags from 38 histone modifications, characterized in CD4+ T cells, to the human genome and calculated their enrichment and depletion in all families of human TEs. We found that several of these families are significantly enriched or depleted for various histone modifications, both active and repressive. The enrichment of human TE families with active histone modifications is consistent with the exaptation hypothesis and stands in contrast to previous analyses that have found mammalian TEs to be exclusively repressively modified. Comparisons between TE families revealed that older families carry more histone modifications than younger ones, another observation consistent with the exaptation hypothesis. However, data from within family analyses on the relative ages of epigenetically modified elements are consistent with both the genome defense and exaptation hypotheses. Finally, TEs located proximal to genes carry more histone modifications than the ones that are distal to genes, as may be expected if epigenetically modified TEs help to regulate the expression of nearby host genes.ConclusionsWith a few exceptions, most of our findings support the exaptation hypothesis for the role of TE epigenetic modifications when vetted against the genome defense hypothesis. The recruitment of epigenetic modifications may represent an additional mechanism by which TEs can contribute to the regulatory functions of their host genomes.

Highlights

  • Transposition is disruptive in nature and, it is imperative for host genomes to evolve mechanisms that suppress the activity of transposable elements (TEs)

  • TE-gene locations and histone modifications The exaptation hypothesis predicts that TEs proximal to host genes would bear more histone modifications than those that are distal to genes, since these modifications are more likely to effect the regulation of the genes

  • Comparison with previous results While most work to date on mammalian histone modifications has focused on non-repetitive DNA, there have been four recent studies on the histone modification status of mammalian repetitive sequence elements, three in mouse [8,20,22] and one in human [19]

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Summary

Introduction

Transposition is disruptive in nature and, it is imperative for host genomes to evolve mechanisms that suppress the activity of transposable elements (TEs). Transposition provides diverse sequences that can be exapted by host genomes as functional elements. These notions form the basis of two competing hypotheses pertaining to the role of epigenetic modifications of TEs in eukaryotic genomes: the genome defense hypothesis and the exaptation hypothesis. We explore the relationship between TEs and the epigenetic regulatory mechanisms that are thought to have evolved in response to their proliferation in eukaryotic genomes [1]. According to the genome defense hypothesis, it be may expected that: (1) younger TEs, that is those that are potentially active, will bear more epigenetic modifications than older inactive TEs; and (2) TEs will bear primarily repressive (gene silencing) modifications rather than active modifications which are associated with gene expression

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