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Ligand-induced native G-quadruplex stabilization impairs transcription initiation.
Conghui Li1, Honghong Wang1, Zhinang Yin1
1Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Genome Research
|August 17, 2021
Summary
This study reveals how guanine-quadruplexes (G4s) dynamically regulate gene transcription genome-wide. G4 stabilization by drugs impacts transcription, offering new therapeutic strategies for diseases.
Area of Science:
- Genomics
- Molecular Biology
- Epigenetics
Background:
- G-quadruplexes (G4s) are DNA structures involved in gene transcription.
- Genome-wide understanding of G4 roles in transcription is limited.
- G4-targeted ligands are explored for DNA-based therapies.
Purpose of the Study:
- To develop a method for genome-wide profiling of native G4s.
- To investigate the relationship between G4s and transcriptional regulation.
- To explore the therapeutic potential of G4 stabilization.
Main Methods:
- Established a sensitive G4-CUT&Tag method for high-resolution, genome-wide G4 profiling.
- Analyzed cell type-specific G4 distribution and association with epigenetic marks.
- Investigated the effects of G4-targeted ligands on RNA polymerase II occupancy and transcription.
Main Results:
- Native G4s are cell type-specific and linked to active regulatory elements.
- Drug-induced RNA polymerase II pausing promotes G4 formation.
- G4 stabilization by ligands globally reduces transcription initiation and alters chromatin states.
Conclusions:
- G4 dynamics and gene transcription exhibit reciprocal genome-wide regulation.
- Ligand-induced G4 stabilization inhibits transcription factor loading.
- Findings deepen understanding of G4 biology for therapeutic applications in human diseases.
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