Histone variants in archaea and the evolution of combinatorial chromatin complexity.

Histone variants in archaea and the evolution of combinatorial chromatin complexity.
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DOI:
10.1073/pnas.2007056117
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发表时间:
2020-12-29
影响因子:
11.1
通讯作者:
Warnecke T
Warnecke T
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Stevens KM;Swadling JB;Hocher A;Bang C;Gribaldo S;Schmitz RA;Warnecke T

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真核生物中的染色质是围绕组蛋白-DNA复合物构建的,组蛋白-DNA复合物充当整合调控信息的平台。不同层次的信息以组合方式整合,例如通过将核心组蛋白交换为具有不同性质的变体。我们发现组蛋白变体也存在于古细菌中。特别是,我们确定了独特的古细菌变体,作为顶石,防止组蛋白-DNA复合物的延伸。重要的是,我们发现一些古菌组蛋白变体是古老的,并且已经作为不同的单位维持了数亿年。我们的工作表明,复杂的组合染色质,使用组蛋白作为其积木存在于真核生物之外,真核生物的祖先可能已经有了复杂的染色质。真核生物的核小体是表观遗传信息动态整合的平台。翻译后修饰被可逆地添加或去除,核心组蛋白被交换为旁系同源变体,这与对转录和基因组可及性的不断变化的需求相一致。组蛋白在古细菌中也很常见。然而,它们在基因组调控中的作用以及个体旁系同源物组装成具有不同性质的组蛋白-DNA复合物的能力仍然知之甚少。在这里,我们结合联合收割机结构建模与系统发育分析揭示古组蛋白旁系同源物,其进化历史,并通过异源寡聚体组装产生组合染色质状态的能力。专注于人类的古细菌系统的模式Methanosphaera stadtmanae,我们表明,可以从它的七个组蛋白旁系同源物组装的异聚体复合物在DNA结合亲和力和四聚体稳定性有很大的不同。使用分子动力学模拟,我们继续确定独特的旁系同源物在M。stadtmanae和史氏甲烷短杆菌,其特征在于二聚体之间的不稳定界面。我们建议,这些旁系同源物作为顶蛋白,防止稳定的四聚体形成和扩展到较长的低聚物的模式古细菌组蛋白的特性。重要的是,我们提供的证据,这些顶石,以及其他旁系同源的甲烷菌目,已经维持了数亿年的古老的复制事件后,基因组结构。总之,我们的研究结果表明,至少有一些古生组蛋白旁系同源物已经进化到发挥独特的和保守的功能作用,让人想起真核组蛋白变体。我们的结论是,组合复杂的组蛋白为基础的染色质并不局限于真核生物,并可能早于他们的出现。
Chromatin in eukaryotes is built around histone–DNA complexes, which act as platforms for the integration of regulatory information. Different layers of information are integrated in a combinatorial fashion, for example by exchanging core histones for variants with different properties. We show that histone variants also exist in archaea. In particular, we identify unique archaeal variants that act as capstones, preventing extension of histone–DNA complexes. Importantly, we show that some archaeal histone variants are ancient and have been maintained as distinct units for hundreds of millions of years. Our work suggests that complex combinatorial chromatin that uses histones as its building blocks exists outside eukaryotes and that the ancestor of eukaryotes might have already had complex chromatin. Nucleosomes in eukaryotes act as platforms for the dynamic integration of epigenetic information. Posttranslational modifications are reversibly added or removed and core histones exchanged for paralogous variants, in concert with changing demands on transcription and genome accessibility. Histones are also common in archaea. Their role in genome regulation, however, and the capacity of individual paralogs to assemble into histone–DNA complexes with distinct properties remain poorly understood. Here, we combine structural modeling with phylogenetic analysis to shed light on archaeal histone paralogs, their evolutionary history, and capacity to generate combinatorial chromatin states through hetero-oligomeric assembly. Focusing on the human commensal Methanosphaera stadtmanae as a model archaeal system, we show that the heteromeric complexes that can be assembled from its seven histone paralogs vary substantially in DNA binding affinity and tetramer stability. Using molecular dynamics simulations, we go on to identify unique paralogs in M. stadtmanae and Methanobrevibacter smithii that are characterized by unstable interfaces between dimers. We propose that these paralogs act as capstones that prevent stable tetramer formation and extension into longer oligomers characteristic of model archaeal histones. Importantly, we provide evidence from phylogeny and genome architecture that these capstones, as well as other paralogs in the Methanobacteriales, have been maintained for hundreds of millions of years following ancient duplication events. Taken together, our findings indicate that at least some archaeal histone paralogs have evolved to play distinct and conserved functional roles, reminiscent of eukaryotic histone variants. We conclude that combinatorially complex histone-based chromatin is not restricted to eukaryotes and likely predates their emergence.
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