Epigenetic histone modifications of human transposable elements: genome defense versus exaptation
Epigenetic histone modifications of human transposable elements: genome defense versus exaptation
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DOI：
10.1186/1759-8753-1-2
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发表时间：
2010-01-01
期刊：
影响因子：
4.9
通讯作者：
Jordan, I. King
中科院分区：
文献类型：
--
作者：
Huda, Ahsan;Marino-Ramirez, Leonardo;Jordan, I. King
背景：转座在本质上是破坏性的，因此，宿主基因组必须进化出抑制转座因子（te）活性的机制。同时，转座也提供了多种序列，可以作为功能元件被宿主基因组期待。这些概念构成了两个相互竞争的假说的基础，这些假说与真核生物基因组中TEs的表观遗传修饰的作用有关：基因组防御假说和摘取假说。迄今为止，所有可用的证据都表明基因组防御假说是TE表观遗传修饰生物学作用的最佳解释。结果：我们利用最近表征的人类基因组表观遗传组蛋白修饰数据，评估了基因组防御假说与提取假说产生的几种预测。为此，我们将CD4+ T细胞中38个组蛋白修饰的染色质免疫沉淀序列标记映射到人类基因组中，并计算了它们在所有人类te家族中的富集和消耗。我们发现，这些家族中有几个在各种组蛋白修饰（包括活性组蛋白修饰和抑制性组蛋白修饰）上显著富集或减少。具有活性组蛋白修饰的人类TE家族的富集与萃取假说一致，与先前发现哺乳动物TE只具有抑制性修饰的分析相反。TE家族之间的比较显示，年龄较大的家族比年轻的家族携带更多的组蛋白修饰，这是另一个与排除假说一致的观察结果。然而，来自家族内部对表观遗传修饰元件的相对年龄的分析数据与基因组防御和提取假设一致。最后，位于基因近端的te比位于基因远端的te携带更多组蛋白修饰，如果表观遗传修饰的te有助于调节附近宿主基因的表达，这是可以预期的。结论：除了少数例外，我们的大多数发现都支持TE表观遗传修饰作用的剔除假说，而不是基因组防御假说。表观遗传修饰的募集可能是te参与宿主基因组调控功能的另一种机制。
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.