Background Transposable elements (TEs) make up half of mammalian genomes and shape genome regulation by harboring binding sites for regulatory factors. These include binding sites for architectural proteins, such as CTCF, RAD21, and SMC3, that are involved in tethering chromatin loops and marking domain boundaries. The 3D organization of the mammalian genome is intimately linked to its function and is remarkably conserved. However, the mechanisms by which these structural intricacies emerge and evolve have not been thoroughly probed. Results Here, we show that TEs contribute extensively to both the formation of species-specific loops in humans and mice through deposition of novel anchoring motifs, as well as to the maintenance of conserved loops across both species through CTCF binding site turnover. The latter function demonstrates the ability of TEs to contribute to genome plasticity and reinforce conserved genome architecture as redundant loop anchors. Deleting such candidate TEs in human cells leads to the collapse of conserved loop and domain structures. These TEs are also marked by reduced DNA methylation and bear mutational signatures of hypomethylation through evolutionary time. Conclusions TEs have long been considered a source of genetic innovation. By examining their contribution to genome topology, we show that TEs can contribute to regulatory plasticity by inducing redundancy and potentiating genetic drift locally while conserving genome architecture globally, revealing a paradigm for defining regulatory conservation in the noncoding genome beyond classic sequence-level conservation.

中文翻译：

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选择转座子有助于使保守的高阶染色体结构永久化

背景 转座因子 (TE) 占哺乳动物基因组的一半，并通过包含调控因子的结合位点来塑造基因组调控。这些包括结构蛋白的结合位点，例如 CTCF、RAD21 和 SMC3，它们参与连接染色质环和标记域边界。哺乳动物基因组的 3D 组织与其功能密切相关，并且非常保守。然而，这些结构复杂性出现和演变的机制尚未得到彻底探讨。结果 在这里，我们表明 TE 通过新锚定基序的沉积对人类和小鼠物种特异性环的形成以及通过 CTCF 结合位点周转维持两个物种的保守环的形成做出了广泛贡献。后一个功能证明了 TE 有助于基因组可塑性和加强保守的基因组结构作为冗余环锚的能力。删除人类细胞中的此类候选 TE 会导致保守的环和域结构的崩溃。这些 TE 的特征还在于 DNA 甲基化减少，并在进化过程中带有低甲基化的突变特征。结论长期以来，TE 一直被认为是基因创新的来源。通过检查它们对基因组拓扑结构的贡献，我们表明 TE 可以通过在局部诱导冗余和增强遗传漂移，同时在全球范围内保护基因组结构来促进调节可塑性，揭示了定义非编码基因组中超越经典序列级保守性的调控保守性的范例。