TY  - JOUR
A1  - Li, Conghui
A1  - Wang, Honghong
A1  - Yin, Zhinang
A1  - Fang, Pingping
A1  - Xiao, Ruijing
A1  - Xiang, Ying
A1  - Wang, Wen
A1  - Li, Qiuzi
A1  - Huang, Beili
A1  - Huang, Jian
A1  - Liang, Kaiwei
T1  - Ligand-induced native G-quadruplex stabilization impairs transcription initiation
Y1  - 2021/09/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1546 
EP  - 1560 
DO  - 10.1101/gr.275431.121 
VL  - 31 
IS  - 9 
UR  - http://genome.cshlp.org/content/31/9/1546.abstract 
N2  - G-quadruplexes (G4s) are noncanonical DNA secondary structures formed through the self-association of guanines, and G4s are distributed widely across the genome. G4 participates in multiple biological processes including gene transcription, and G4-targeted ligands serve as potential therapeutic agents for DNA-targeted therapies. However, genome-wide studies of the exact roles of G4s in transcriptional regulation are still lacking. Here, we establish a sensitive G4-CUT&Tag method for genome-wide profiling of native G4s with high resolution and specificity. We find that native G4 signals are cell type–specific and are associated with transcriptional regulatory elements carrying active epigenetic modifications. Drug-induced promoter-proximal RNA polymerase II pausing promotes nearby G4 formation. In contrast, G4 stabilization by G4-targeted ligands globally reduces RNA polymerase II occupancy at gene promoters as well as nascent RNA synthesis. Moreover, ligand-induced G4 stabilization modulates chromatin states and impedes transcription initiation via inhibition of general transcription factors loading to promoters. Together, our study reveals a reciprocal genome-wide regulation between native G4 dynamics and gene transcription, which will deepen our understanding of G4 biology toward therapeutically targeting G4s in human diseases. 
ER  -