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G-quadruplex structural variations in human genome associated with single-nucleotide variations and their impact on gene activity
- Source :
- Proc Natl Acad Sci U S A
- Publication Year :
- 2021
- Publisher :
- Proceedings of the National Academy of Sciences, 2021.
-
Abstract
- 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.
- Subjects :
- Transcriptional Activation
0301 basic medicine
dbSNP
Regulatory Sequences, Nucleic Acid
Biology
010402 general chemistry
G-quadruplex
Polymorphism, Single Nucleotide
01 natural sciences
03 medical and health sciences
Transcription (biology)
Genetic variation
Humans
Promoter Regions, Genetic
Enhancer
Gene
Genetics
Multidisciplinary
Genome, Human
Biological Sciences
0104 chemical sciences
DNA-Binding Proteins
G-Quadruplexes
030104 developmental biology
Gene Expression Regulation
Nucleic acid
Nucleic Acid Conformation
Human genome
Transcription Initiation Site
Protein Binding
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 118
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....e13956de9ba46cccb9e638a4a9f3e61f