Promoter G-quadruplexes and transcription factors cooperate to shape the cell type-specific transcriptome
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Abstract
Cell identity is maintained by activation of cell-specific gene programs, regulated by epigenetic marks, transcription factors and chromatin organization. DNA G-quadruplex (G4)-folded regions in cells were reported to be associated with either increased or decreased transcriptional activity. By G4-ChIP-seq/RNA-seq analysis on liposarcoma cells we confirmed that G4s in promoters are invariably associated with high transcription levels in open chromatin. Comparing G4 presence, location and transcript levels in liposarcoma cells to available data on keratinocytes, we showed that the same promoter sequences of the same genes in the two cell lines had different G4-folding state: high transcript levels consistently associated with G4-folding. Transcription factors AP-1 and SP1, whose binding sites were the most significantly represented in G4-folded sequences, coimmunoprecipitated with their G4-folded promoters. Thus, G4s and their associated transcription factors cooperate to determine cell-specific transcriptional programs, making G4s to strongly emerge as new epigenetic regulators of the transcription machinery.
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G4s hold various regulatory functions in transcription and translation.
“However, G4s hold various regulatory functions in transcription and translation (20)”
From G-quadruplex-mediated genomic instability drives SNVs in cancer (2024) · cites this paper as [20]
The Introduction and Results describe several ways G4s may regulate transcription, including effects on RNA polymerase, transcription-factor binding, and gene expression. The passages do not establish a regulatory role in translation; the Results discuss 5′UTRs in relation to transcription, not protein synthesis. (LLM, conf=0.86)
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DNA G-quadruplex structures: more than simple roadblocks to transcription?
Robinson, J., Raguseo, F., Nuccio, S. P., Liano, D., & Antonio, M. D. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab609 · Cited by 312 · see citing works
“Specifically, 98% of G4s identified by BG4ChIP coincided with NDRs, an observation that has now been recapitulated in independent studies (17).”
BackgroundInfluentialDynamic alternative DNA structures in biology and disease
Wang, G., & Vasquez, K. M. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-022-00539-9 · Cited by 196 · see citing works
Genome-wide mapping of G-quadruplex structures with CUT&Tag
Lyu, J., Shao, R., Yung, P. Y. K., & Elsässer, S. J. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab1073 · Cited by 225 · see citing works
G-quadruplex DNA structure is a positive regulator of MYC transcription
Esain-Garcia, I., Kirchner, A., Melidis, L., Tavares, R. D. C. A., Dhir, S., Simeone, A., Yu, Z., Madden, S. K., Hermann, R., Tannahill, D., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2320240121 · Cited by 147 · see citing works
“In vitro experiments have suggested transcription can lead to G4 folding (21); however, G4s are still observed in cells when transcription is inhibited (22, 23).”
G-Quadruplexes and Their Ligands: Biophysical Methods to Unravel G-Quadruplex/Ligand Interactions
Santos, T. A. B. D., Salgado, G. F. J., Cabrita, E. J., & Cruz, C. (2021) · Pharmaceuticals · doi:10.3390/ph14080769 · Cited by 138 · see citing works
“The location of those G4 structures was revealed using an antibodybased G4 chromatin immunoprecipitation sequencing (G4 ChIP–seq) approach [21], and suggests that they play a crucial role in critical cellular processes such as DNA replication [29,30], DNA damage repair [26], transcription [22,23], translation [31] and…”
BackgroundSequencing and characterizing short tandem repeats in the human genome
Tanudisastro, H., Deveson, I. W., Dashnow, H., & MacArthur, D. G. (2024) · Nature reviews genetics · doi:10.1038/s41576-024-00692-3 · Cited by 108 · see citing works
“GC-rich repeats in promoter regions can form stable G4 quadruplexes 19,20 that regulate transcriptional activity.”
Leuzzi, G., Vasciaveo, A., Taglialatela, A., Chen, X., Firestone, T. M., Hickman, A. R., Mao, W., Thakar, T., Vaitsiankova, A., Huang, J., et al. (2024) · Cell · doi:10.1016/j.cell.2024.01.008 · Cited by 108 · see citing works
G-quadruplex DNA structures in human stem cells and differentiation
Zyner, K. G., Simeone, A., Flynn, S. M., Doyle, C., Marsico, G., Adhikari, S., Portella, G., Tannahill, D., & Balasubramanian, S. (2022) · Nature Communications · doi:10.1038/s41467-021-27719-1 · Cited by 122 · see citing works
Zanin, I., Ruggiero, E., Nicoletto, G., Lago, S., Maurizio, I., Gallina, I., & Richter, S. N. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad626 · Cited by 101 · see citing works
Self-citationG-Quadruplex-Binding Proteins: Promising Targets for Drug Design
Shu, H.-L., Zhang, R., Xiao, K., Yang, J., & Sun, X. (2022) · Biomolecules · doi:10.3390/biom12050648 · Cited by 78 · see citing works
“Notably, G4s and their associated transcription factors cooperate to shape the cell-specific transcriptome [29,84].”
BackgroundG-Quadruplex Targeting in the Fight against Viruses: An Update
Ruggiero, E., Zanin, I., Terreri, M., & Richter, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222010984 · Cited by 74
“Increasing evidence supports a possible G4 involvement in both cases [19,113,114]; however, the mechanisms underneath still need to be elucidated.”
BackgroundSelf-citationCell-free DNA fragmentomics in cancer
Tsui, W., Jiang, P., & Lo, Y. M. D. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.09.006 · Cited by 63 · see citing works
Noncanonical DNA structures are drivers of genome evolution
Makova, K. D., & Weissensteiner, M. H. (2023) · Trends in Genetics · doi:10.1016/j.tig.2022.11.005 · Cited by 94 · see citing works
Wulfridge, P., & Sarma, K. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01437-4 · Cited by 64 · see citing works
“G4 presence at promoters is also strongly correlated with higher expression 60 .”
Mitochondria and G-quadruplex evolution: an intertwined relationship
Sahayasheela, V. J., Yu, Z., Hidaka, T., Pandian, G. N., & Sugiyama, H. (2022) · Trends in Genetics · doi:10.1016/j.tig.2022.10.006 · Cited by 67 · see citing works
G-quadruplex resolution: From molecular mechanisms to physiological relevance
Sato, K., & Knipscheer, P. (2023) · DNA repair · doi:10.1016/j.dnarep.2023.103552 · Cited by 64 · see citing works
Wang, W.-M., Li, D.-D., Xu, Q.-Q., Cheng, J., Yu, Z., Li, G.-Y., Qiao, S., Pan, J.-S., Wang, H., Shi, J., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45353-5 · Cited by 56 · see citing works
Wang, K., Liu, Y., Li, J., Xiao, C., Wang, Y., Gu, W., Li, Y., Xia, Y., Yan, T., Yang, M.-H., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33761-4 · Cited by 64 · see citing works
Advances and challenges in identifying and characterizing G-quadruplex–protein interactions
Dai, Y., Teng, X., Zhang, Q., Hou, H., & Li, J. (2023) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2023.06.007 · Cited by 46 · see citing works
LINE-1 regulates cortical development by acting as long non-coding RNAs
Mangoni, D., Simi, A., Lau, P., Armaos, A., Ansaloni, F., Codino, A., Damiani, D., Floreani, L., Carlo, V. D., Vozzi, D., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40743-7 · Cited by 39 · see citing works
Wang, K.-B., Liu, Y., Li, Y., Dickerhoff, J., Li, J., Yang, M.-H., Yang, D., & Kong, L.-Y. (2022) · Journal of the American Chemical Society · doi:10.1021/jacs.2c00435 · Cited by 36 · see citing works
Navigating the complexity of Polycomb repression: Enzymatic cores and regulatory modules
Tamburri, S., Rustichelli, S., Amato, S., & Pasini, D. (2024) · Molecular Cell · doi:10.1016/j.molcel.2024.07.030 · Cited by 40 · see citing works
An Upstream G-Quadruplex DNA Structure Can Stimulate Gene Transcription
Chen, Y., Simeone, A., Melidis, L., Cuesta, S. M., Tannahill, D., & Balasubramanian, S. (2024) · ACS Chemical Biology · doi:10.1021/acschembio.3c00775 · Cited by 39 · see citing works
Fatma, K., Thumpati, P., Panda, D., Velayutham, R., & Dash, J. (2024) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.3c00537 · Cited by 34
Targeting G-quadruplexes to achieve antiviral activity
Ruggiero, E., & Richter, S. N. (2022) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2022.129085 · Cited by 56 · see citing works
Self-citationG-quadruplexes are promoter elements controlling nucleosome exclusion and RNA polymerase II pausing
Esnault, C., Aabidine, A. Z. E., Robert, M.-C., Cucchiarini, A., Magat, T., Pigeot, A., Bouchouika, S., García-Oliver, E., Gawron, K., Basyuk, E., et al. (2023) · bioRxiv · doi:10.1038/s41588-025-02263-6 · Cited by 32 · see citing works
Georgakopoulos-Soares, I., Chan, C. S. Y., Ahituv, N., & Hemberg, M. (2022) · Genome Biology · doi:10.1186/s13059-022-02727-6 · Cited by 30 · see citing works
“higher expression levels and open chromatin [105], the degree to which non-B DNA”
BackgroundMonsen, R. C., Chua, E. Y. D., Hopkins, J. B., Chaires, J. B., & Trent, J. O. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad014 · Cited by 33 · see citing works
“Promoter G4s have emerged as a new layer of epigenetic transcriptional control that influence both cell-type (76) and cell-state (77).”
Optical control of gene expression using a DNA G-quadruplex targeting reversible photoswitch
Zhang, X., Dhir, S., Melidis, L., Chen, Y., Yu, Z., Simeone, A., Spiegel, J., Adhikari, S., & Balasubramanian, S. (2025) · Nature Chemistry · doi:10.1038/s41557-025-01792-1 · Cited by 31 · see citing works
G-quadruplex DNA contributes to RNA polymerase II-mediated 3D chromatin architecture
Yuan, J., He, X.-M., & Wang, Y.-S. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad588 · Cited by 26 · see citing works
Short LNA-modified oligonucleotide probes as efficient disruptors of DNA G-quadruplexes
Chowdhury, S., Wang, J., Nuccio, S. P., Mao, H., & di Antonio, M. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac569 · Cited by 26
“More recently, work by the Richter group has further corroborated these observations across different cell lines, which is consistent with the notion that promoter-G4s act as transcriptional regulators (11).”
BackgroundGenome-wide mapping of G-quadruplex DNA: a step-by-step guide to select the most effective method
Galli, S., Flint, G., Růžičková, L., & Antonio, M. D. (2024) · RSC Chemical Biology · doi:10.1039/d4cb00023d · Cited by 32 · see citing works
Ahmed, A., Chen, S., Roman-Escorza, M., Angell, R., Oxenford, S., Mcconville, M., Barton, N., Sunose, M., Neidle, D. M., Haider, S., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-54080-2 · Cited by 25 · see citing works
Promoter R-Loops Recruit U2AF1 to Modulate Its Phase Separation and RNA Splicing
He, X., Yuan, J. J., Gao, Z., & Wang, Y. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.3c08204 · Cited by 23 · see citing works
Tian, Y., Wang, W., Lautrup, S., Zhao, H., Li, X., Law, P. W. N., Dinh, N., Fang, E. F., Cheung, H., & Chan, W. (2022) · Nature Communications · doi:10.1038/s41467-022-33012-6 · Cited by 26 · see citing works
Zareie, A. R., Dabral, P., & Verma, S. (2024) · Pathogens · doi:10.3390/pathogens13010060 · Cited by 23 · see citing works
“Furthermore, the interactions between G4s and viral structural proteins extend beyond specific recognition, impacting the structural integrity of the viral capsid or envelope.”
BackgroundPapp, C., Mukundan, V. T., Jenjaroenpun, P., Winnerdy, F. R., Ow, G. S., Phan, A. T., & Kuznetsov, V. A. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad252 · Cited by 23 · see citing works
“The ability of G4s to regulate transcription has been well documented in recent publications (76,77,85).”
BackgroundIn-Depth Sequence Analysis of Bread Wheat VRN1 Genes
Strejčková, B., Milec, Z., Holušová, K., Cápal, P., Vojtková, T., Čegan, R., & Šafář, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212284 · Cited by 26 · see citing works
“A growing number of results suggest the involvement of G4s in transcription regu‐ lation and were recently suggested as new epigenetic regulators of transcription [46,47].”
BackgroundNicoletto, G., Terreri, M., Maurizio, I., Ruggiero, E., Cernilogar, F. M., Vaine, C. A., Cottini, M. V., Shcherbakova, I., Penney, E., Gallina, I., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae797 · Cited by 22 · see citing works
“Then, beads with immunoprecipitated chromatin were washed five times with ice-cold wash buffer and DNA was de-cross-linked and purified as indicated elsewhere ( 19 ).”
InfluentialSelf-citationAhmed, A., Greenhalf, W., Palmer, D., Williams, N., Worthington, J., Arshad, T., Haider, S., Alexandrou, E., Guneri, D., Waller, Z., et al. (2023) · Molecules · doi:10.3390/molecules28062452 · Cited by 22 · see citing works
Li, C., Yin, Z., Xiao, R., Huang, B., Cui, Y., Wang, H., Xiang, Y., Wang, L., Lei, L., Ye, J., et al. (2022) · Genome biology · doi:10.1186/s13059-022-02830-8 · Cited by 24 · see citing works
“G4s can interact with a variety of endogenous proteins including transcription factors, general transcription factors, DNA helicases, and epigenetic and chromatin remodelers to achieve specific biological readouts [17, 32].”
BackgroundRNA G-quadruplex forming regions from SARS-2, SARS-1 and MERS coronoviruses
Kabbara, A., Vialet, B., Marquevielle, J., Bonnafous, P., Mackereth, C. D., & Amrane, S. (2022) · Frontiers in Chemistry · doi:10.3389/fchem.2022.1014663 · Cited by 22
“Many studies proved their impact on various biological processes such as gene expression mechanisms (Lago et al., 2021).”
BackgroundA Phenotypic Approach to the Discovery of Potent G-Quadruplex Targeted Drugs
Neidle, S. (2024) · Molecules · doi:10.3390/molecules29153653 · Cited by 27 · see citing works
G-quadruplex-mediated genomic instability drives SNVs in cancer
Richl, T., Kuper, J., & Kisker, C. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae098 · Cited by 20 · see citing works
“However, G4s hold various regulatory functions in transcription and translation ( 20 ), deregulated or ligand-induced G4-formation is associated with the activation of DNA-damage responses, implying that aberrant G4-formation triggers similar pathways as DNA-damage ( 83 ).”
BackgroundRoxo, C., & Pasternak, A. (2024) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2024.130038 · Cited by 20
Phase Separation Modulates the Formation and Stabilities of DNA Guanine Quadruplex
Gao, Z., Yuan, J., He, X.-M., Wang, H., & Wang, Y.-S. (2023) · JACS Au · doi:10.1021/jacsau.3c00106 · Cited by 20
Non-canonical DNA in human and other ape telomere-to-telomere genomes
Smeds, L., Kamali, K., Kejnovská, I., Kejnovský, E., Chiaromonte, F., & Makova, K. D. (2024) · bioRxiv · doi:10.1101/2024.09.02.610891 · Cited by 19
Robinson, J., Flint, G., Garner, I., Galli, S., Maher, T. E., Kuimova, M. K., Vilar, R., McNeish, I. A., Brown, R. E., Keun, H. C., et al. (2025) · Genome biology · doi:10.1186/s13059-025-03654-y · Cited by 19 · see citing works
“Interestingly, the total number of G4 peaks obtained in PEO4 cells was twofold lower when compared to PEO1 cells, with the latter producing 12,984 G4 peaks compared to 6,392 peaks in PEO4 cells.”
G-Quadruplexes in Nuclear Biomolecular Condensates
Pavlova, I., Iudin, M. S., Surdina, A. V., Severov, V. V., & Varizhuk, A. M. (2023) · Genes · doi:10.3390/genes14051076 · Cited by 22 · see citing works
“The G4s appear to play context-dependent permissive/repressive roles in the gene expression, thus contributing to the cell-type-specific transcription control [9,13].”
BackgroundEffects of G-Quadruplex-Binding Plant Secondary Metabolites on c-MYC Expression
Zenkov, R., Kirsanov, K., Ogloblina, A., Vlasova, O., Naberezhnov, D., Karpechenko, N. Y., Fetisov, T., Lesovaya, E., Belitsky, G., Dolinnaya, N. G., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169209 · Cited by 19 · see citing works
“, who showed that promoter sequences of the same genes in two cell lines had a different G4 folding state depending on the degree of chromatin opening [11,21].”
BackgroundResearch on Werner Syndrome: Trends from Past to Present and Future Prospects
Tsuge, K., & Shimamoto, A. (2022) · Genes · doi:10.3390/genes13101802 · Cited by 21 · see citing works
“It has been reported that the G-rich sequences that form G-quadruplexe structures are scattered in genomic regions other than telomeres at chromosome ends, and that they are involved in the regulation of gene expression [46].”
BackgroundG-quadruplexes as pivotal components of cis-regulatory elements in the human genome
Zhang, R., Wang, Y., Wang, C., Sun, X., & Mergny, J. (2024) · bioRxiv · doi:10.1186/s12915-024-01971-5 · Cited by 17 · see citing works
“Computational studies have shown that G4s are not randomly distributed in the human genome; instead, they are concentrated in functional regions such as promoters [9], telomeres [10], and intron-exon borders [11], suggesting that G4s may have biological functions.”
BackgroundFeng, Y.-L., He, Z., Luo, Z., Sperti, F., Valverde, I. E., Zhang, W.-L., & Monchaud, D. (2023) · iScience · doi:10.1016/j.isci.2023.106846 · Cited by 17 · see citing works
The Dynamic Regulation of G-Quadruplex DNA Structures by Cytosine Methylation
Stevens, A., de Jong, L., & Kennedy, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052407 · Cited by 17 · see citing works
“Recent research is supporting this role, and has suggested that G4s may act as an epigenetic mark responsible, at least in part, for the recruitment of SP1 [52].”
BackgroundEvolutionary dynamics of predicted G-quadruplexes in human and other great apes
Mohanty, S. K., Chiaromonte, F., & Makova, K. D. (2025) · Genome biology · doi:10.1186/s13059-025-03635-1 · Cited by 18 · see citing works
“The enrichment of G4s we found at promoters corroborates previous studies [93, 96, 107].”
G-quadruplex ligands as potent regulators of lysosomes
Ferret, L., Alvarez-Valadez, K., Rivière, J., Muller, A., Bohálová, N., Yu, L., Guittat, L., Brázda, V., Kroemer, G., Mergny, J., et al. (2023) · Autophagy · doi:10.1080/15548627.2023.2170071 · Cited by 15 · see citing works
“In favor of this conjecture, it has been proposed that G4 folding state can regulate cell type-specific biological effects [8].”
BackgroundBidula, S. M. (2021) · Cytokine · doi:10.1016/j.cyto.2021.155493 · Cited by 16 · see citing works
“The same paper identified that expression of IL1B, IL6, IL7, CXCL8, FGF1, CSF2, CSF3, CXCL10, CCL2, TNF, and VEGFA were upregulated, whilst IL18 and PDGF were downregulated [13] .”
BackgroundPrediction of G4 formation in live cells with epigenetic data: a deep learning approach
Korsakova, A., & Phan, A. (2023) · bioRxiv · doi:10.1093/nargab/lqad071 · Cited by 14 · see citing works
The Intertwined Role of 8-oxodG and G4 in Transcription Regulation
Gorini, F., Ambrosio, S., Lania, L., Majello, B., & Amente, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032031 · Cited by 14 · see citing works
Lorenzatti, A., Piga, E. J., Gismondi, M., Binolfi, A., Margarit, E., Calcaterra, N., & Armas, P. (2022) · bioRxiv · doi:10.1093/nar/gkad948 · Cited by 14 · see citing works
“Bearing in mind that G4s and the transcription factors associated with them cooperate to specify differential transcriptional programs ( 26 ), gains / losses or structural conversions of G4s generated by the presence of SNVs could not only alter a G4 structure but also influence gene expression…”
BackgroundStilp, A., Scherer, M., König, P., Fürstberger, A., Kestler, H., & Stamminger, T. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010748 · Cited by 14 · see citing works
“revealing that G4s are enriched at AP-1 binding sites and involved in transcriptional regulation at these sites [59] as well as our results showing enriched G4-forming sequences at AP-1 sites identified in the ATAC-seq (S5 Fig).”
BackgroundDNA G-quadruplexes: Structural and functional insights
Jonchhe, S., Lahiri, S., & Rothenberg, E. (2025) · DNA repair · doi:10.1016/j.dnarep.2025.103910 · Cited by 12 · see citing works
Long G4-rich enhancers target promoters via a G4 DNA-based mechanism
DeMeis, J. D., Roberts, J., Delcher, H. A., Godang, N. L., Coley, A. B., Brown, C. L., Shaw, M. H., Naaz, S., Dahal, A., Alqudah, S. Y., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae1180 · Cited by 13 · see citing works
Cordero, J., Swaminathan, G., Rogel-Ayala, D. G., Rubio, K., Elsherbiny, A., Mahmood, S., Szymański, W., Graumann, J., Braun, T., Günther, S., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54740-x · Cited by 13 · see citing works
“Further, as G4 has been shown to cooperate with transcription factors at gene promoters 20,21 , we analyzed publicly available NGS data generated using different methods for the assessment of G4 formation (Fig.”
Wang, X., Chen, S., Zhao, Z.-Y., Chen, F., Huang, Y., Guo, X., Lei, L.-C., Wang, W., Luo, Y.-X., Yu, H.-C., et al. (2022) · iScience · doi:10.1016/j.isci.2022.105312 · Cited by 13 · see citing works
“In transcription regulation, G4 was found to facilitate the adherence of transcription initiation complex, increase promoter-proximal Pol II pausing, control CpG island methylation and interact with transcription factors (Lago et al., 2021; Li et al., 2021; Lyu et al., 2021; Mao et al., 2018).”
Strejčková, B., Mazzucotelli, E., Čegan, R., Milec, Z., Brus, J., Çakır, E., Mastrangelo, A., Özkan, H., & Šafář, J. (2023) · Frontiers in Plant Science · doi:10.3389/fpls.2022.1106164 · Cited by 12
“Several studies in animals observed the direct role of G4 motifs in the regulation of replication, transcription, and mi-RNA expression (Huppert and Balasubramanian, 2007; Maizels and Gray, 2013; Valton et al., 2014; Lago et al., 2021; Spiegel et al., 2021; Zhu et al., 2021).”
BackgroundIso-FRET: an isothermal competition assay to analyze quadruplex formation in vitro
Luo, Y., Verga, D., & Mergny, J. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac465 · Cited by 12
Ruggiero, E., Frasson, I., Tosoni, E., Scalabrin, M., Perrone, R., Marušič, M., Plavec, J., & Richter, S. N. (2022) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.1c00508 · Cited by 21 · see citing works
Self-citationInteraction between non-coding RNAs, mRNAs and G-quadruplexes
Ghafouri-Fard, S., Abak, A., Baniahmad, A., Hussen, B., Taheri, M., Jamali, E., & Dinger, M. (2022) · Cancer Cell International · doi:10.1186/s12935-022-02601-2 · Cited by 12 · see citing works
“G quadruplex-folded has binding sites of transcription factors activator protein-1 (AP-1) and specificity protein-1 (Sp1), therefore being associated with determination of cell-specific transcriptional programs [13].”
BackgroundMethodological advances of bioanalysis and biochemical targeting of intracellular G‐quadruplexes
Teng, X.-C., Dai, Y.-C., & Li, J.-H. (2022) · Exploration · doi:10.1002/exp.20210214 · Cited by 12
A Compendium of G-Flipon Biological Functions That Have Experimental Validation
Herbert, A. G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910299 · Cited by 13 · see citing works
“Indeed, recent findings suggest that it is GQ formation that recruits TFs to transcriptional hubs [117].”
BackgroundCharacterising tandem repeat complexities across long-read sequencing platforms with TREAT and otterPreprint
Tesi, N., Salazar, A., Zhang, Y., van der Lee, S. J., Hulsman, M., Knoop, L., Wijesekera, S., Křížová, J., Schneider, A.-F. E., Pennings, M., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.15.585288 · Cited by 3 · see citing works
Roy, S. S., Bagri, S., Vinayagamurthy, S., Sengupta, A., Then, C. R., Kumar, R., Sridharan, S., & Chowdhury, S. (2024) · eLife · doi:10.7554/elife.96216 · Cited by 17 · see citing works
“…of transcription factors and RNA polymerase or via alteration of DNA accessibility by modulating the epigenetic state of the gene promoters ( Hussain et al., 2017 ; Kumar et al., 2011 ; Lago et al., 2021 ; Mukherjee et al., 2019 ; Saha et al., 2017 ; Sharma et al., 2021 ; Varshney et al., 2020 ).”
BackgroundG-quadruplex-dependent transcriptional regulation by molecular condensation in the Bcl3 promoter
Yoo, W., Song, Y.-W., Bansal, V., & Kim, K. K. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf827 · Cited by 10
“Although generally considered a ubiquitous TF, SP1 plays a crucial role in cell-type-specific gene expression programs and is frequently overexpressed in various cancers [ 19 , 97– 99 ].”
Maurizio, I., Ruggiero, E., Zanin, I., Conflitti, M., Nicoletto, G., Provvedi, R., & Richter, S. N. (2025) · Nature Communications · doi:10.1038/s41467-025-62485-4 · Cited by 10 · see citing works
“Our fi ndings show that G4 location within the genome exerts different effects on transcription: G4s embedded in gene bodies, as in Mtb , mediate repression of transcription, while those at promoters, as in human cells, promote transcription by enhancing transcription factor binding 25,31,61,62 .”
Self-citationThompson, M. D., & Byrd, A. K. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf678 · Cited by 11 · see citing works
“Binding of proteins to these DNA secondary structures can modulate processes such as transcription [ 4 , 5 ], and resolution of these secondary structures is crucial to safeguarding genomic stability [ 23 , 24 ] (reviewed in [ 25 ]).”
Karam, J. A. Q., Fréreux, C., Mohanty, B., Dalton, A., Dincman, T., Palanisamy, V., Howley, B. V., & Howe, P. H. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107830 · Cited by 10 · see citing works
“PCBP1-DHX9 interactions occur at promoter regions G4 forming sequences are found throughout the genome and our data demonstrates that PCBP1 preferentially binds to promoter DNA near TSSs where G4 structure formation can both negatively and positively regulate RNA Pol II progression (39).”
BackgroundCheng, J. C., Swarup, N., Morselli, M., Huang, W.-L., Aziz, M. A., Caggiano, C., Kordi, M., Patel, A. A., Chia, D., Kim, Y., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae276 · Cited by 8 · see citing works
“Functionally, G-Quad structures have been associated with open chromatin regions near promoters and with increased transcription through specific recognition by transcription factors ( 63 ,64 ).”
Bisoi, A., Sarkar, S., & Singh, P. C. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.131050 · Cited by 10
Neupane, A., Chariker, J. H., & Rouchka, E. C. (2023) · Genes · doi:10.3390/genes14122125 · Cited by 12 · see citing works
“Though the involvement of G4s in gene transcription [58,61,62,64,65,89,107] and telomere regulation [16,17,29,35,108] is well studied, the mechanism of base excision repair by DNA glycosylases in G4s and other non-canonical structures is poorly understood [109,110].”
Lista, M., Jousset, A.-C., Cheng, M.-P., Saint-André, V., Perrot, E., Rodrigues, M., Primo, C. D., Gadelle, D., Toccafondi, E., Ségéral, E., et al. (2023) · Retrovirology · doi:10.1186/s12977-023-00625-8 · Cited by 10 · see citing works
“In the human genome, ChIPseq studies have revealed hundreds of thousands of G4s, and their enrichment in nucleosome-depleted regions, promoters and 5′UTR of highly transcribed genes [25, 26].”
BackgroundNuccio, S. P., Cadoni, E., Nikoloudaki, R., Galli, S., Ler, A.-J., Sanchez-Cabanillas, C., Maher, T. E., Fan, E., Guneri, D., Flint, G., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-67074-z · Cited by 22 · see citing works
Pérez-Soto, M., Ramos-Soriano, J., Peñalver, P., Belmonte-Reche, E., O'Hagan, M. P., Cucchiarini, A., Mergny, J., Galan, M. C., López, M. C. L., Thomas, M. D. C., et al. (2024) · European journal of medicinal chemistry · doi:10.1016/j.ejmech.2024.116641 · Cited by 9
Oxidative DNA damage on the VEGF G‐quadruplex forming promoter is repaired via long‐patch BER
Hussen, A. S., Kravitz, H. L., Freudenthal, B., & Whitaker, A. M. (2023) · Environmental and Molecular Mutagenesis · doi:10.1002/em.22570 · Cited by 10 · see citing works
“…under certain conditions such as upon specific stress stimuli, during certain stages of the cell cycle, in a cell type-specific manner, and/or upon interaction with proteins that bind and stabilize or resolve them (Biffi et al., 2013; Lago et al., 2021; Shu et al., 2022; Varshney et al., 2020).”
BackgroundBisoi, A., & Singh, P. (2023) · Journal of Physical Chemistry Letters · doi:10.1021/acs.jpclett.3c00214 · Cited by 9
Sodium Ions as Regulators of Transcription in Mammalian Cells
Lopina, O. D., Fedorov, D. A., Sidorenko, S. V., Bukach, O. V., & Климанова, Е. А. (2022) · Biochemistry (Moscow) · doi:10.1134/s0006297922080107 · Cited by 8 · see citing works
“The location of such guanine-rich sequences (G-tracks) in the genome is not random; they have been found in functionally important regions [71], for example, in gene promoters [72].”
BackgroundModulating gene expression in breast cancer via DNA secondary structure and the CRISPR toolbox
Kretzmann, J. A., Irving, K. L., Smith, N. M., & Evans, C. W. (2021) · NAR Cancer · doi:10.1093/narcan/zcab048 · Cited by 14 · see citing works
Quadrupia provides a comprehensive catalog of G-quadruplexes across genomes from the tree of life
Chantzi, N., Nayak, A., Baltoumas, F. A., Aplakidou, E., Liew, S. W., Galuh, J. E., Patsakis, M., Montgomery, A., Moeckel, C., Mouratidis, I., et al. (2025) · Genome Research · doi:10.1101/gr.279790.124 · Cited by 8
“…that G4s are involved in processes such as gene regulation (Huppert et al. 2008; Brooks et al. 2010; Hänsel-Hertsch et al. 2016; Lee et al. 2020; Lago et al. 2021; Robinson et al. 2021; Shen et al. 2021; Spiegel et al. 2021; Georgakopoulos-Soares et al. 2022a,b; Li et al. 2023), alternative…”
Bidzińska, J., Pietro, L. D., Naghshineh, E., Pandini, C., Doria, F., Zaffaroni, N., Gandellini, P., Neidle, S., & Folini, M. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07908-2 · Cited by 8 · see citing works
Complete analysis of G-quadruplex forming sequences in the gapless assembly of human chromosome Y.
Dobrovolná, M., Mergny, J.-L., & Brázda, V. (2024) · Biochimie · doi:10.1016/j.biochi.2024.10.007 · Cited by 8
Peng, H., Zhang, Y.-S., Luo, Q., Wang, X., & You, H.-J. (2024) · Biophysics Reports · doi:10.52601/bpr.2024.240018 · Cited by 8 · see citing works
“…with particular enrichment in cancer-related genes and regions with somatic copy number amplifications, such as c-MYC (Hänsel-Hertsch et al. 2016; Lago et al. 2021; Zheng et al. 2020). c-MYC c-MYC , a proto-oncogene with transcription factor activity, plays a critical role in cancer progression…”
BackgroundG-Quadruplex Matters in Tissue-Specific Tumorigenesis by BRCA1 Deficiency
Kim, S., & Hwang, S. (2022) · Genes · doi:10.3390/genes13030391 · Cited by 8 · see citing works
“While two cell lines have different G4-folding states in the same loci, high transcript levels are consistently associated with G4-folding, and TF binding sites are highly enriched within G4 ChIP peaks [93].”
BackgroundNon-B DNA structures and their contributions to genetic diversity, aging, and disease
Bochalis, E., Dereki, I., Wang, G., Sgourou, A., Vásquez, K. M., & Georgakopoulos‐Soares, I. (2026) · Nucleic Acids Research · doi:10.1093/nar/gkag084 · Cited by 7 · see citing works
“Studies have shown that non-B DNA motifs can regulate gene expression through multiple mechanisms, including controlling transcription factor binding, nucleosome positioning, epigenetic modification regulation, and modulating splicing and translation [ 11 , 21 , 62 , 125 –132 , 136 –139 ] (Fig.”
Evolutionary Dynamics of G-Quadruplexes in Human and Other Great Ape Telomere-to-Telomere Genomes
Mohanty, S., Chiaromonte, F., & Makova, K. D. (2024) · bioRxiv · doi:10.1101/2024.11.05.621973 · Cited by 7
“The enrichment of G4s we found at promoters corroborates previous studies (Huppert and Balasubramanian 2007; Lago et al. 2021; Wu et al. 2021).”
The age‐related decline of helicase function—how G‐quadruplex structures promote genome instability
Frobel, J., & Hänsel‐Hertsch, R. (2024) · FEBS Letters · doi:10.1002/1873-3468.14939 · Cited by 6 · see citing works
G-quadruplex forming motifs in the promoter region of the B-MYB proto-oncogene.
Miranda, A., Cucchiarini, A., Esnault, C., Andrau, J., Oliveira, P. A., Mergny, J., & Cruz, C. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.132244 · Cited by 7 · see citing works
The Characterization of G-Quadruplexes in Tobacco Genome and Their Function under Abiotic Stress
Song, K., Li, B., Li, H., Zhang, R., Zhang, X., Luan, R., Liu, Y., & Yang, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084331 · Cited by 7 · see citing works
“Therefore, the dynamic changes of G-quadruplex stability in the DEG promoter under drought stress and salt stress may be the potential mechanism for tobacco to cope with these two abiotic stresses.”
BackgroundChoudhury, S. D., Kumar, P., & Choudhury, D. (2023) · Naunyn-Schmiedeberg's Archives of Pharmacology · doi:10.1007/s00210-023-02857-z · Cited by 7
“There are about 736,689 identified G4 structures in the human genome, of which a large number are associated with the gene promoter and telomere regions and epigenetically regulate transcription (Zhang et al. 2008, Lago et al. 2021a).”
G4-DNA formation and chromatin remodelling are interdependent in human cells
Lawler, N. B., Ou, A., King, J. J., Evans, C. W., Iyer, K. S., & Smith, N. M. (2023) · Chemical Science · doi:10.1039/d3sc02533k · Cited by 10 · see citing works
Structural and Functional Classification of G-Quadruplex Families within the Human Genome
Neupane, A., Chariker, J., & Rouchka, E. (2023) · bioRxiv · doi:10.3390/genes14030645 · Cited by 7 · see citing works
“Over the past three decades, guanine-rich quadruplex sequences have been implicated as key structural regulators of gene expression, cellular differentiation, transcription factors, and their cell line and tissue specificity [2].”
BackgroundInfluential
- Authors
- Lago, S., Nadai, M., Cernilogar, F. M., Kazerani, M., Domíniguez Moreno, H., Schotta, G., & Richter, S. N.
- Affiliations
- University of Padua (IT)
- Ludwig-Maximilians-Universität München (DE)
- Corresponding author
- Lago, Sara
- Schotta, Gunnar
- Richter, Sara N.
- Venue
- Nature Communications
- Published
- 2021-06-23
- Volume
- 12
- Issue
- 1
- Pages
- 3885-3885
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC8222265
- OpenAlex
- W3173676343
- Cited by
- 269
- References
- 97
- Citations by year
- 2026: 26 · 2025: 53 · 2024: 72 · 2023: 65 · 2022: 41 · 2021: 10 · 2012: 1
- FWCI
- 14.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Padua Research Archive (University of Padova) (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (213249687, SFB1064, SFB1321, 329628492)
- Associazione Italiana per la Ricerca sul Cancro (21850)
- Fondazione Italiana per la Ricerca sul Cancro (21850)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- G-quadruplex, transcription factors, cell type-specific transcriptome, epigenetic regulation of transcription, AP-1, Sp1, keratinocytes, chromatin accessibility
- MeSH terms
- Base Sequence, Binding Sites, Cell Line, DNA, Humans, Nucleic Acid Conformation, Promoter Regions, Genetic, Protein Binding, Transcription Factors, Sp1 Transcription Factor, Transcription Factor AP-1, Gene Expression Profiling, Cell Line, Tumor, G-Quadruplexes, Transcriptome
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