G‑quadruplexes as regulatory platforms for human transcription factors: insights from ChIP-seq data
4 affiliations
- 1Institute of Biophysics, Czech Academy of Sciences, Královopolská 135, Brno, 612 00 Czech Republic
- 2Faculty of Chemistry, Brno University of Technology, Purkyňova 118, Brno, 612 00 Czech Republic
- 3National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, Brno, 62500 Czech Republic
- 4Laboratoire d’Optique et Biosciences, Ecole Polytechnique, CNRS, Inserm, Institut Polytechnique de Paris, Palaiseau, 91120 France
Abstract
Background: G-quadruplexes (G4s) are non-canonical DNA structures with important regulatory functions. While several transcription factors have been shown to interact with G4s, a comprehensive understanding of this interaction network remains elusive.
Results: Here, we integrated genome-wide predictions of highly stable G-quadruplex sequences with 32,817 ChIP-seq datasets from ChIP-Atlas to systematically map transcription factors and transcription-associated chromatin proteins linked to G4-rich regions in the human genome. Highly stable G4 motifs are non-randomly distributed, showing strong enrichment in gene-dense chromosomes, at promoters, regulatory regions, and repeat elements. Integration with transcription factor binding profiles revealed a broad spectrum of G4-associated proteins, including established interactors such as STAT3, TP53 and CTCF, and the transcription-associated chromatin regulator BRD4, as well as previously unrecognized candidates such as REST, NR3C1, FLI1, and HSF1. Unexpectedly, only a minority of transcription factors were consistently depleted from G4 regions.
Conclusions: Our results indicate that G-quadruplex-prone sequences represent a common genomic feature associated with a number of human transcription factors and chromatin-associated regulatory proteins and support a model in which G4-rich regions act as selective regulatory scaffolds shaping transcription factor occupancy and gene regulation.
Graphical abstract:
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12864-026-13217-5.
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BibTeX
@article{drapalova2026gquadruplexes,
title = {{G‑quadruplexes as regulatory platforms for human transcription factors: insights from ChIP-seq data}},
author = {Karolína Drápalová and Michaela Dobrovolná and Filip Kledus and Jean-Louis Mergny and Václav Brázda},
journal = {BMC Genomics},
year = {2026},
month = jul,
doi = {10.1186/s12864-026-13217-5},
url = {https://doi.org/10.1186/s12864-026-13217-5},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - G‑quadruplexes as regulatory platforms for human transcription factors: insights from ChIP-seq data
AU - Karolína Drápalová
AU - Michaela Dobrovolná
AU - Filip Kledus
AU - Jean-Louis Mergny
AU - Václav Brázda
PY - 2026
DA - 2026/07/29
JO - BMC Genomics
DO - 10.1186/s12864-026-13217-5
UR - https://doi.org/10.1186/s12864-026-13217-5
AB - Background: G-quadruplexes (G4s) are non-canonical DNA structures with important regulatory functions. While several transcription factors have been shown to interact with G4s, a comprehensive understanding of this interaction network remains elusive. Results: Here, we integrated genome-wide predictions of highly stable G-quadruplex sequences with 32,817 ChIP-seq datasets from ChIP-Atlas to systematically map transcription factors and transcription-associated chromatin proteins linked to G4-rich regions in the human genome. Highly stable G4 motifs are non-randomly distributed, showing strong enrichment in gene-dense chromosomes, at promoters, regulatory regions, and repeat elements. Integration with transcription factor binding profiles revealed a broad spectrum of G4-associated proteins, including established interactors such as STAT3, TP53 and CTCF, and the transcription-associated chromatin regulator BRD4, as well as previously unrecognized candidates such as REST, NR3C1, FLI1, and HSF1. Unexpectedly, only a minority of transcription factors were consistently depleted from G4 regions. Conclusions: Our results indicate that G-quadruplex-prone sequences represent a common genomic feature associated with a number of human transcription factors and chromatin-associated regulatory proteins and support a model in which G4-rich regions act as selective regulatory scaffolds shaping transcription factor occupancy and gene regulation. Graphical abstract: Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12864-026-13217-5.
SN - 1471-2164
ER -