Epigenetic histone modifications of human transposable elements: genome defense versus exaptation

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.

Transposable elements are the primary source of novelty in primate gene regulation

“…Although previous studies have suggested the recruitment of TEs as functional elements (Huda et al 2010;Lynch et al 2011Lynch et al , 2015Jacques et al 2013;Chuong et al 2016), we demonstrated, and functionally validated, the extent of this phenomenon in primates, demonstrating that LTRs and SVAs have played an important role in rewiring ape gene regulation. In contrast, only a minor fraction of evolutionarily conserved CREs overlap an annotated TE.…”

Evolution of Genome Content: Population Dynamics of Transposable Elements in Flies and Humans

“…Traditionally, histone modifications have been considered to provide a molecular mechanism for TE silencing in plants, fungi, and mammals including humans (10, 98-100). However, a recent study in humans suggests that histone modifications may also represent an additional mechanism by which TEs can contribute to the regulatory functions of the host genome (101). In Drosophila, the relationship of histone modifications with TE expression has not been demonstrated (102).…”

A Brief History of the Status of Transposable Elements: From Junk DNA to Major Players in Evolution

“…It is now clear that DNA methylation of cytosines, histone modifications, and RNA interference, all interdependent mechanisms associated with chromatin conformation, can switch TEs on or off. These processes must therefore play a role not only in defending the genome against invasion by TEs and retroviruses, but also in the complex interactions involved in gene regulation throughout development (Huda et al 2010), as reported for neuronal development, as well as in developmental processes in mouse oocytes and preimplantation embryos (Muotri et al 2007;Sasaki et al 2008). The possibility remains, however, that the presence of the TEs in many eukaryote genomes is also the result of their having been selected as components of (inactive) heterochromatin because of their importance in chromosomal biology and cell division (Biémont 2009).…”