Transposable elements contribute to cell and species-specific chromatin looping and gene regulation in mammalian genomes
Transposable elements contribute to cell and species-specific chromatin looping and gene regulation in mammalian genomes
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DOI：
10.1038/s41467-020-15520-5
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发表时间：
2020-04-14
影响因子：
16.6
通讯作者：
Boyle, Alan P.
中科院分区：
文献类型：
--
作者：
Diehl, Adam G.;Ouyang, Ningxin;Boyle, Alan P.
染色质循环对于基因调控非常重要，对跨物种和细胞类型的 3D 染色质结构的研究提高了我们对控制染色质循环原理的理解。然而，3D 基因组进化及其与自然选择的关系在很大程度上仍未得到探索。在哺乳动物中，CTCF 蛋白定义了大多数染色质环的边界，CTCF 占据的变化与环分歧相关。虽然许多 CTCF 结合位点属于转座元件 (TE)，但它们对 3D 染色质结构进化的贡献尚不清楚。在这里，我们报告了 TE 驱动的 CTCF 结合位点扩展对人类和小鼠中保守和发散的染色质环的相对贡献。我们证明，TE 衍生的 CTCF 结合分歧可以解释大部分可变环。这些可变环对跨细胞和物种的相应基因表达变异性有显着贡献，可能是通过细化负责细胞类型特异性增强子-启动子相互作用的亚TAD规模环接触来实现的。一部分哺乳动物 CTCF 结合位点属于转座元件 (TE)，但它们对 3D 染色质结构进化的贡献尚不清楚。在这里，作者研究了 TE 驱动的 CTCF 结合位点扩展对人类和小鼠染色质循环的影响，并提供证据表明 TE 有助于细胞特异性和物种特异性染色质循环多样性以及哺乳动物基因组中的可变基因调控。
Chromatin looping is important for gene regulation, and studies of 3D chromatin structure across species and cell types have improved our understanding of the principles governing chromatin looping. However, 3D genome evolution and its relationship with natural selection remains largely unexplored. In mammals, the CTCF protein defines the boundaries of most chromatin loops, and variations in CTCF occupancy are associated with looping divergence. While many CTCF binding sites fall within transposable elements (TEs), their contribution to 3D chromatin structural evolution is unknown. Here we report the relative contributions of TE-driven CTCF binding site expansions to conserved and divergent chromatin looping in human and mouse. We demonstrate that TE-derived CTCF binding divergence may explain a large fraction of variable loops. These variable loops contribute significantly to corresponding gene expression variability across cells and species, possibly by refining sub-TAD-scale loop contacts responsible for cell-type-specific enhancer-promoter interactions. A fraction of mammalian CTCF binding sites fall within transposable elements (TEs) but their contribution to the evolution of 3D chromatin structure is unknown. Here the authors investigate the effect of TE-driven CTCF binding site expansions on chromatin looping in humans and mice, and provide evidence that TEs contribute to cell-specific and species-specific chromatin looping diversity and variable gene regulation in mammalian genomes.