A hypothetical model of trans-acting R-loops-mediated promoter-enhancer interactions by Alu elements

作     者：Xue Bai Feifei Li Zhihua Zhang Xue Bai;Feifei Li;Zhihua Zhang

作者机构：CAS Key Laboratory of Genome Sciences and InformationBeijing Institute of GenomicsChinese Academy of SciencesChina National Center for BioinformationBeijing 100101China School of Life ScienceUniversity of Chinese Academy of SciencesBeijing 100101China School of Artificial IntelligenceUniversity of Chinese Academy of SciencesBeijing 100101China 

出 版 物：《Journal of Genetics and Genomics》 (遗传学报（英文版）)

年 卷 期：2021年第48卷第11期

页      面：1007-1019页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 1001[医学-基础医学(可授医学、理学学位)] 071007[理学-遗传学] 

基　　金：the National Natural Science Foundation of China of China(91940304,31871331,31671342) Beijing Natural Science Foundation(Z200021) Special Investigation on Science and Technology Basic Resources of MOST,China(2019FY100102) the National Key R&D Program of China(2018YFC2000400) the Beijing Advanced Discipline Fund(115200S001)。 

主　　题：Alu Enhancer-promoter interaction eRNA R-loop 

摘      要：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-loops 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-loop 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.