Structural Polymorphism of Guanine Quadruplex-Containing Regions in Human Promoters
Intramolecular guanine quadruplexes (G4s) are non-canonical nucleic acid structures formed by four guanine (G)-rich tracts that assemble into a core of stacked planar tetrads. G4-forming DNA sequences are enriched in gene promoters and are implicated in the control of gene expression. Most G4-formin...
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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/16020 |
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| author | Christopher Hennecker Lynn Yamout Chuyang Zhang Chenzhi Zhao David Hiraki Nicolas Moitessier Anthony Mittermaier |
| author_facet | Christopher Hennecker Lynn Yamout Chuyang Zhang Chenzhi Zhao David Hiraki Nicolas Moitessier Anthony Mittermaier |
| author_sort | Christopher Hennecker |
| collection | DOAJ |
| description | Intramolecular guanine quadruplexes (G4s) are non-canonical nucleic acid structures formed by four guanine (G)-rich tracts that assemble into a core of stacked planar tetrads. G4-forming DNA sequences are enriched in gene promoters and are implicated in the control of gene expression. Most G4-forming DNA contains more G residues than can simultaneously be incorporated into the core resulting in a variety of different possible G4 structures. Although this kind of structural polymorphism is well recognized in the literature, there remain unanswered questions regarding possible connections between G4 polymorphism and biological function. Here we report a detailed bioinformatic survey of G4 polymorphism in human gene promoter regions. Our analysis is based on identifying G4-containing regions (G4CRs), which we define as stretches of DNA in which every residue can form part of a G4. We found that G4CRs with higher degrees of polymorphism are more tightly clustered near transcription sites and tend to contain G4s with shorter loops and bulges. Furthermore, we found that G4CRs with well-characterized biological functions tended to be longer and more polymorphic than genome-wide averages. These results represent new evidence linking G4 polymorphism to biological function and provide new criteria for identifying biologically relevant G4-forming regions from genomic data. |
| first_indexed | 2024-03-09T16:19:17Z |
| format | Article |
| id | doaj.art-f70e62397346401c8ca4043aa8cc777b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:19:17Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f70e62397346401c8ca4043aa8cc777b2023-11-24T15:31:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241602010.3390/ijms232416020Structural Polymorphism of Guanine Quadruplex-Containing Regions in Human PromotersChristopher Hennecker0Lynn Yamout1Chuyang Zhang2Chenzhi Zhao3David Hiraki4Nicolas Moitessier5Anthony Mittermaier6Department of Chemistry, McGill University, Montreal, QC H3A 0B8, CanadaDepartment of Chemistry, McGill University, Montreal, QC H3A 0B8, CanadaDepartment of Chemistry, McGill University, Montreal, QC H3A 0B8, CanadaDepartment of Chemistry, McGill University, Montreal, QC H3A 0B8, CanadaDepartment of Chemistry, McGill University, Montreal, QC H3A 0B8, CanadaDepartment of Chemistry, McGill University, Montreal, QC H3A 0B8, CanadaDepartment of Chemistry, McGill University, Montreal, QC H3A 0B8, CanadaIntramolecular guanine quadruplexes (G4s) are non-canonical nucleic acid structures formed by four guanine (G)-rich tracts that assemble into a core of stacked planar tetrads. G4-forming DNA sequences are enriched in gene promoters and are implicated in the control of gene expression. Most G4-forming DNA contains more G residues than can simultaneously be incorporated into the core resulting in a variety of different possible G4 structures. Although this kind of structural polymorphism is well recognized in the literature, there remain unanswered questions regarding possible connections between G4 polymorphism and biological function. Here we report a detailed bioinformatic survey of G4 polymorphism in human gene promoter regions. Our analysis is based on identifying G4-containing regions (G4CRs), which we define as stretches of DNA in which every residue can form part of a G4. We found that G4CRs with higher degrees of polymorphism are more tightly clustered near transcription sites and tend to contain G4s with shorter loops and bulges. Furthermore, we found that G4CRs with well-characterized biological functions tended to be longer and more polymorphic than genome-wide averages. These results represent new evidence linking G4 polymorphism to biological function and provide new criteria for identifying biologically relevant G4-forming regions from genomic data.https://www.mdpi.com/1422-0067/23/24/16020G4G4CRbioinformaticstranscription start siteTSS |
| spellingShingle | Christopher Hennecker Lynn Yamout Chuyang Zhang Chenzhi Zhao David Hiraki Nicolas Moitessier Anthony Mittermaier Structural Polymorphism of Guanine Quadruplex-Containing Regions in Human Promoters International Journal of Molecular Sciences G4 G4CR bioinformatics transcription start site TSS |
| title | Structural Polymorphism of Guanine Quadruplex-Containing Regions in Human Promoters |
| title_full | Structural Polymorphism of Guanine Quadruplex-Containing Regions in Human Promoters |
| title_fullStr | Structural Polymorphism of Guanine Quadruplex-Containing Regions in Human Promoters |
| title_full_unstemmed | Structural Polymorphism of Guanine Quadruplex-Containing Regions in Human Promoters |
| title_short | Structural Polymorphism of Guanine Quadruplex-Containing Regions in Human Promoters |
| title_sort | structural polymorphism of guanine quadruplex containing regions in human promoters |
| topic | G4 G4CR bioinformatics transcription start site TSS |
| url | https://www.mdpi.com/1422-0067/23/24/16020 |
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