CGGBP1-Regulated Heterogeneous C-T Transition Rates Correlate with G-quadruplex Potential of Terrestrial Vertebrate Genomes.

Authors

Praveen Kumar, Umashankar Singh

Published in

Journal of molecular evolution. Jul 28, 2026. Epub Jul 28, 2026.

Abstract

The formation of G-quadruplexes (G4) is fundamentally linked to DNA GC content. With no reports of evolutionary selection of G4 stabilizing genes, it is arguable that G4 formation depends primarily on inherent sequence properties. Vertebrate promoters are notable for their consistently high GC-content as well as pronounced G/C strand asymmetry. Genomic GC content has changed in the course of evolution of terrestrial vertebrates, especially the amniotes, but its relationship with the potential to form G4 remains less well understood. By analyzing genomes of 101 amniotes we report that lineage-specific differences in association between GC-content and G4 formation potential (pG4) in amniotes are concentrated at 1 kb promoter regions. To understand a possible mechanistic relationship underlying high GC-concentrations in pG4 of mammalian and avian promoters, we test the role of selective cytosine methylation restriction leading to G/C-retention. Such a function has been reported for CGGBP1, a protein involved in mitigation of cytosine methylation as well as G4-formation. By analyzing promoterome-wide C-T transition rates at TFBSs in pG4s we show that mammalian and avian CGGBP1s preserve C through methylation restriction. Our approach involves a combined meta-analysis of (i) genomes and promoters of 101 amniote genomes classified into reptilian, avian and mammalian classes through PQS finder and FIMO for 1019 JASPAR vertebrate motifs, (ii) recently reported global cytosine methylation patterns affected by overexpression of amniotic or non-amniotic forms of CGGBPs, (iii) and PWM reconstruction of motifs differentially enriched in pG4s showing homeothermic specific GC-retention. Our findings suggest that cytosine methylation restriction by CGGBP1 contributes to the G4-forming profiles of vertebrate promoters by preserving C on the G4-complementary strand resulting in minute differences in TFBSs across amniotes.

PMID:
42517877
Bibliographic data and abstract were imported from PubMed on 28 Jul 2026.

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