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

机译:人类转座因子的表观遗传组蛋白修饰:基因组防御与分离

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Background Transposition 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. Results We 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. Conclusions With 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.
机译:背景技术转座本质上是破坏性的,因此,宿主基因组必须发展抑制转座因子(TEs)活性的机制。同时,转座还提供了多种序列,这些序列可以被宿主基因组用作功能元件。这些概念构成了两个相互竞争的假说的基础,这两个假说与TE在真核基因组中的表观遗传修饰的作用有关:基因组防御假说和逃逸假说。迄今为止,所有可用证据均表明基因组防御假设是TE表观遗传修饰的生物学作用的最佳解释。结果我们使用人类基因组的最近表征的表观遗传组蛋白修饰数据,评估了由基因组防御假设相对于免除假设产生的几种预测。为此,我们将38种组蛋白修饰的染色质免疫沉淀序列标签(以CD4 + T细胞为特征)映射到人类基因组,并计算了它们在人类TEs所有家族中的富集和耗竭。我们发现这些家族中的几个家族因活跃和抑制性的各种组蛋白修饰而明显富集或耗尽。具有活跃的组蛋白修饰的人类TE家族的富集与分离假说是一致的,并且与先前的分析相反,后者发现哺乳动物TEs仅被抑制性修饰。 TE家庭之间的比较显示,老年家庭比年轻家庭携带更多的组蛋白修饰,这是与假说相符的另一观察结果。然而,来自家庭内部分析的关于表观遗传修饰元素相对年龄的数据与基因组防御和逃逸假说是一致的。最后,位于基因近端的TE携带的组蛋白修饰比远离基因的TE携带的组蛋白修饰更多,这是可以预期的,如果表观遗传修饰的TE有助于调节附近宿主基因的表达。结论除少数例外,我们的大多数发现都支持了关于基因组防御假说审查TE表观遗传修饰作用的假说。表观遗传修饰的募集可能代表了TE可以通过其参与宿主基因组调控功能的另一种机制。

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