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

作　　者：Xue Bai Feifei Li Zhihua Zhang 

机构地区：[1]CAS Key Laboratory of Genome Sciences and Information,Beijing Institute of Genomics,Chinese Academy of Sciences,China National Center for Bioinformation,Beijing 100101,China [2]School of Life Science,University of Chinese Academy of Sciences,Beijing 100101,China [3]School of Artificial Intelligence,University of Chinese Academy of Sciences,Beijing 100101,China

出　　处：《Journal of Genetics and Genomics》2021年第11期1007-1019,共13页遗传学报（英文版）

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)。

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.

关 键 词：ALU Enhancer-promoter interaction eRNA R-loop 

分 类 号：Q75[生物学—分子生物学]