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DOI	10.1073/pnas.2013230118
	G-quadruplex structural variations in human genome associated with single-nucleotide variations and their impact on gene activity
	Gong J.-Y.; Wen C.-J.; Tang M.-L.; Duan R.-F.; Chen J.-N.; Zhang J.-Y.; Zheng K.-W.; He Y.-D.; Hao Y.-H.; Yu Q.; Ren S.-P.; Tan Z.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:21
英文摘要	G-quadruplexes (G4s) formed by guanine-rich nucleic acids play a role in essential biological processes such as transcription and replication. Besides the >1.5 million putative G-4–forming sequences (PQSs), the human genome features >640 million single-nucleotide variations (SNVs), the most common type of genetic variation among people or populations. An SNV may alter a G4 structure when it falls within a PQS motif. To date, genome-wide PQS–SNV interactions and their impact have not been investigated. Herein, we present a study on the PQS–SNV interactions and the impact they can bring to G4 structures and, subsequently, gene expressions. Based on build 154 of the Single Nucleotide Polymorphism Database (dbSNP), we identified 5 million gains/losses or structural conversions of G4s that can be caused by the SNVs. Of these G4 variations (G4Vs), 3.4 million are within genes, resulting in an average load of >120 G4Vs per gene, preferentially enriched near the transcription start site. Moreover, >80% of the G4Vs overlap with transcription factor–binding sites and >14% with enhancers, giving an average load of 3 and 7.5 for the two regulatory elements, respectively. Our experiments show that such G4Vs can significantly influence the expression of their host genes. These results reveal genome-wide G4Vs and their impact on gene activity, emphasizing an understanding of genetic variation, from a structural perspective, of their physiological function and pathological implications. The G4Vs may also provide a unique category of drug targets for individualized therapeutics, health risk assessment, and drug development. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	G-quadruplexes \| single nucleotide variations \| genetic variations
语种	英语
scopus关键词	guanine quadruplex; transcription factor; DNA binding protein; guanine quadruplex; protein binding; Article; binding site; controlled study; DNA structure; gene activity; gene expression; gene identification; gene interaction; gene loss; genetic association; genetic transcription; genetic variation; human; human genome; priority journal; single nucleotide polymorphism; conformation; gene expression regulation; genetics; human genome; promoter region; regulatory sequence; single nucleotide polymorphism; transcription initiation; transcription initiation site; ultrastructure; DNA-Binding Proteins; G-Quadruplexes; Gene Expression Regulation; Genome, Human; Humans; Nucleic Acid Conformation; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Protein Binding; Regulatory Sequences, Nucleic Acid; Transcription Initiation Site; Transcriptional Activation
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251173
作者单位	State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China; Graduate School, University of Chinese Academy of Sciences, Beijing, 100049, China; Beijing Institute of Transfusion Medicine, Beijing, 100850, China; College of Life Sciences, Wuhan University, Wuhan, 430072, China; College Central Laboratory, Changzhi Medical College, Changzhi, Shanxi, 046000, China; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Guangzhou, 510275, China; Center for Healthy Aging, Changzhi Medical College, Changzhi, Shanxi, 046000, China
推荐引用方式 GB/T 7714	Gong J.-Y.,Wen C.-J.,Tang M.-L.,et al. G-quadruplex structural variations in human genome associated with single-nucleotide variations and their impact on gene activity[J],2021,118(21).
APA	Gong J.-Y..,Wen C.-J..,Tang M.-L..,Duan R.-F..,Chen J.-N..,...&Tan Z..(2021).G-quadruplex structural variations in human genome associated with single-nucleotide variations and their impact on gene activity.Proceedings of the National Academy of Sciences of the United States of America,118(21).
MLA	Gong J.-Y.,et al."G-quadruplex structural variations in human genome associated with single-nucleotide variations and their impact on gene activity".Proceedings of the National Academy of Sciences of the United States of America 118.21(2021).