A hypothetical model of trans-acting R-loops-mediated promoter-enhancer interactions by Alu elements
A hypothetical model of trans-acting R-loops-mediated promoter-enhancer interactions by Alu elements
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Alu 元件反式作用 R 环介导的启动子-增强子相互作用的假设模型
DOI：
10.1016/j.jgg.2021.07.005
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发表时间：
2021-11-20
影响因子：
5.9
通讯作者：
Zhang, Zhihua
中科院分区：
文献类型：
--
作者：
Bai, Xue;Li, Feifei;Zhang, Zhihua
增强子通过与启动子相互作用来调节基因表达。文献中的增强子-启动子相互作用(Epis)模型涉及许多组分的活性，包括转录因子和核酸。然而，序列相似性在EPIS中所起的作用在很大程度上仍未被探索。在此，我们报道了Alu衍生序列主导了增强子和启动子之间的序列相似性。在拒绝了可供选择的DNA：DNA和DNA：RNA三链模型后，我们认为增强子相关RNA(ERNAs)可能通过在这些Alu序列上形成反式作用R-Ioop来直接接触其目标启动子。我们展示了功能基因组数据的特征分布，如RNA-DNA邻近连接读数、转录因子的结合和RNA结合蛋白，都与EPIS的Alu序列一致。我们还证明了这些比对的Alu序列可能受到共同进化的限制，进一步暗示了这些R-Ioop杂交体的功能意义。最后，我们的结果表明Erna和Alu元素以一种以前在Epis和哺乳动物基因调控网络进化中未被认识到的方式相互关联。版权所有(C)2021，中国科学院遗传与发育生物学研究所，中国遗传学会。爱思唯尔有限公司和科学出版社出版。版权所有。
Enhancers modulate gene expression by interacting with promoters. Models of enhancer-promoter interactions (EPIs) in the literature involve the activity of many components, including transcription factors and nucleic acid. However, the role that sequence similarity plays in EPIs remains largely unexplored. Herein, we report that Alu-derived sequences dominate sequence similarity between enhancers and promoters. After rejecting alternative DNA:DNA and DNA:RNA triplex models, we propose that enhancer-associated RNAs (eRNAs) may directly contact their targeted promoters by forming trans-acting R-Ioops at those Alu sequences. We show how the characteristic distribution of functional genomic data, such as RNA-DNA proximate ligation reads, binding of transcription factors, and RNA-binding proteins, all align with the Alu sequences of EPIs. We also show that these aligned Alu sequences may be subject to the constraint of coevolution, further implying the functional significance of these R-Ioop hybrids. Finally, our results imply that eRNA and Alu elements associate in a manner previously unrecognized in EPIs and the evolution of gene regulation networks in mammals. Copyright (C) 2021, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.