Identification and characterization of a flexile G-quadruplex in the distal promoter region of stemness gene REX1

Roy, Ananya; Basu, Debadrita; Bose, Debopriya; Dutta, Anindya; Dastidar, Shubhra Ghosh; Chatterjee, Subhrangsu

doi:10.1016/j.ijbiomac.2023.123263

Cited by 7 publications

(1 citation statement)

References 52 publications

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“…CNBP unfolds the G4 structure present on the TCOF1 promoter Works from several groups including ours have recently reported that the impact of CNBP on transcription could be related to its ability to unfold G4 structures present on promoters 9,[34][35][36] . From these ndings we evaluated the in uence of CNBP on parallel G4s present on the TCOF1 EPR.…”

Section: G4s Forming Sequences Present On the Tcof1 Gene Regulates Tr...mentioning

confidence: 99%

The transcription of TCOF1 , the main gene associated with Treacher-Collins syndrome, is regulated by G-quadruplexes and Cellular Nucleic acid Binding Protein (CNBP)

Rosas,

Centola,

Mouguelar

et al. 2024

Preprint

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Treacle ribosome biogenesis factor 1 (TCOF1) is responsible for about 80% of mandibular dysostosis (MD) cases. We have formerly identified a correlation between TCOF1 and CNBP (CCHC-type zinc finger nucleic acid binding protein) expression in human mesenchymal cells. Given the established role of CNBP in gene regulation during rostral development, we explored the potential for CNBP to modulate TCOF1 transcription. Computational analysis for CNBP binding sites (CNBP-BSs) in the TCOF1 promoter revealed several putative binding sites, two of which (Hs791 and Hs2160) overlap with putative G-quadruplex (G4) sequences (PQSs). We validated the folding of these PQSs measuring circular dichroism and fluorescence of appropriate synthetic oligonucleotides. In vitro studies confirmed binding of purified CNBP to the target PQSs (both folded as G4 and unfolded) with Kd values in the nM range. ChIP assays conducted in HeLa cells chromatin detected the CNBP binding to TCOF1 promoter. Transient transfections of HEK293 cells revealed that Hs2160 cloned upstream SV40 promoter increased transcription of downstream firefly luciferase reporter gene. We also detected a CNBP-BS and PQS (Dr2393) in the zebrafish TCOF1 orthologue promoter (nolc1). Disrupting this G4 in zebrafish embryos by microinjecting DNA antisense oligonucleotides complementary to Dr2393 reduced the transcription of nolc1 and recapitulated the craniofacial anomalies characteristic of Treacher Collins Syndrome. Both cnbp overexpression and Morpholino-mediated knockdown in zebrafish induced nolc1 transcription. These results suggest that CNBP modulates the transcriptional expression of TCOF1 through a mechanism involving G-quadruplex folding/unfolding, and that this regulation is active in vertebrates as distantly related as bony fish and humans. These findings may have implications for understanding and treating MD.

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Section: G4s Forming Sequences Present On the Tcof1 Gene Regulates Tr...mentioning

confidence: 99%

The transcription of TCOF1 , the main gene associated with Treacher-Collins syndrome, is regulated by G-quadruplexes and Cellular Nucleic acid Binding Protein (CNBP)

Rosas,

Centola,

Mouguelar

et al. 2024

Preprint

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show abstract

Advances and prospects of natural dietary polyphenols as G-quadruplex stabilizers in biomedical applications

Ye,

Zhang,

Xiang

et al. 2024

International Journal of Biological Macromolecules

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Molecular mechanisms behind BRACO19 and human telomeric G-quadruplex interaction

Libera,

Fasolato,

Ripanti

et al. 2024

Spectrochimica Acta Part A: Molecular and Biomolecular Spectros

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Identification and characterization of a flexile G-quadruplex in the distal promoter region of stemness gene REX1

Cited by 7 publications

References 52 publications

The transcription of TCOF1 , the main gene associated with Treacher-Collins syndrome, is regulated by G-quadruplexes and Cellular Nucleic acid Binding Protein (CNBP)

The transcription of TCOF1 , the main gene associated with Treacher-Collins syndrome, is regulated by G-quadruplexes and Cellular Nucleic acid Binding Protein (CNBP)

Advances and prospects of natural dietary polyphenols as G-quadruplex stabilizers in biomedical applications

Molecular mechanisms behind BRACO19 and human telomeric G-quadruplex interaction

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