Fig. 7: Risk variants disrupt G4s and SP1 binding to promote tumor cell growth.
From: ssG4-seq for global profiling of strand-specific G-quadruplex structures in mammalian genomes
a Venn diagram illustrating the overlap between ICGC mutations and SP1-binding G4 peaks in human K562 cells. b Mutation classification showing G4-stabilizing variants (enhanced SP1 binding) versus G4-disrupting variants (reduced SP1 binding). c Risk variants affected genes and the corresponding mutations in promoters. d Diagram of luciferase reporter assay for characterizing the influences of G4 structures and the corresponding risk variants. G4-disrupting risk variants significantly reduce luciferase reporter activity (e) and the RNA expression levels (qPCR, f). g qPCR showing significantly reduced transcription of CNDP2 and TUSC2 genes in the homozygous mutants compared to wild-type (WT) cells. h Cell growth curve analysis showing significantly increased proliferation rate of the homozygous mutant cells. Reduced G4 formation (BG4 ChIP-qPCR, i) and SP1 binding (SP1 ChIP-qPCR, j) at endogenous promoters containing the risk variants. k, l Knockdown of SP1 or mutation of G4 structures impaired chromatin looping between the TUSC2-TE14707 and CNDP2-TE10132 pairs. n  =  3 biological replicates. Data in e–l are the mean ± s.d., n  =  3 biological replicates, two-tailed unpaired Student’s t-test. Source data are provided as a Source Data file.
