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Updated: Aug 5, 2026
05:37
Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
Published on: April 4, 2025
CGGBP1-Regulated Heterogeneous C-T Transition Rates Correlate with G-quadruplex Potential of Terrestrial Vertebrate
Praveen Kumar1, Umashankar Singh2
1Department of Biological Sciences and Engineering, Indian Institute of Technology Gandhinagar, Gandhinagar, Gujarat, 382055, India.
Journal of Molecular Evolution
|July 28, 2026
Summary
G-quadruplexes (G4) formation in vertebrate promoters is linked to GC content. CGGBP1 protein restricts cytosine methylation, preserving G4 potential in mammalian and avian promoters during evolution.
Area of Science:
- Genomics
- Evolutionary Biology
- Molecular Biology
Background:
- G-quadruplex (G4) formation is intrinsically tied to DNA's GC content.
- Vertebrate promoters exhibit high GC content and strand asymmetry.
- Evolutionary changes in genomic GC content, particularly in amniotes, and their impact on G4 potential are not fully understood.
Purpose of the Study:
- To investigate lineage-specific associations between GC content and G4 formation potential (pG4) in amniote promoter regions.
- To explore the mechanistic role of selective cytosine methylation restriction in maintaining high GC concentrations in mammalian and avian promoters.
- To understand the function of CGGBP1 in mitigating cytosine methylation and influencing G4 formation.
Main Methods:
- Meta-analysis of 101 amniote genomes, focusing on promoter regions and utilizing PQS finder and FIMO for vertebrate motifs.
- Analysis of global cytosine methylation patterns influenced by CGGBP1 overexpression.
- Reconstruction of position weight matrices (PWMs) for motifs enriched in G4-forming regions (pG4s) to identify GC-retention patterns.
Main Results:
- Lineage-specific differences in GC content and pG4 association are concentrated in 1kb promoter regions across 101 amniotes.
- Mammalian and avian CGGBP1 proteins preserve cytosine through methylation restriction, contributing to GC retention in promoters.
- Analysis of C-T transition rates at transcription factor binding sites (TFBSs) within pG4s confirmed CGGBP1's role in maintaining GC content.
Conclusions:
- Selective cytosine methylation restriction by CGGBP1 plays a significant role in shaping the G4-forming profiles of vertebrate promoters.
- CGGBP1 preserves cytosine on the G4-complementary strand, leading to subtle but evolutionarily relevant differences in TFBSs across amniotes.
- This mechanism highlights an interplay between epigenetic regulation (cytosine methylation) and sequence-based DNA structures (G4s) in promoter evolution.
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