Fig. 2

a G4 ViCAR sequencing R2 plotted over G4 ChIP-seq peaks [17] in hESCs (left). H3K27me3 ViCAR sequencing R2 plotted over G4 ChIP-seq peaks is shown for comparison (right). Regions with (G4 +) and without (G4 −) G4 ChIP peaks in accessible regions (ATAC-seq peaks; ATAC +) that contain sequences capable of forming G4s in vitro (called Observed Quadruplex Sequences, OQS +) are shown. BG4 ViCAR normalized R2 signal is enriched at G4 + sites compared to G4 − sites. By contrast, H3K27me3 ViCAR normalized R2 signal mostly accumulates at G4 − sites. b G4 ViCAR sequencing R1 (i.e., 3D interactions) plotted over ChIP-seq and ATAC-seq peaks. c WT and mutant sequence of a G4 oligonucleotide derived from a sequence in an intron of C1orf116. d Circular dichroism (CD) spectra of oligonucleotides corresponding to WT and mutant G4 motifs are consistent with a G4 structure in the WT (K⁺-dependent positive peak at ~ 265 nm and negative peak at ~ 240 nm) and a loss of G4 structure in the mutant (with a shift towards 280 nm). e–g G4 ViCAR data from K562 cells at the edited G4 site in WT and 2 G4 mutant clones. In e, the edited G4 site is highlighted by orange shading, and genes affected by the G4 mutation (j) are highlighted by blue shading. 2D tracks in e show G4 ViCAR R2, and the bottom 3 tracks show loops called by FitHiChIP at 10 kb resolution (q < 0.01). f G4 ViCAR R2 signal in WT and 2 G4 mutant clones at the edited site. The edited G4 motif is shown by a black bar. g Fold change and p values represent R2 signal at the edited site vs R2 signal at 3 control G4 sites (KRAS, MYC, STAT3). HiCAR data from K562 cells at the edited G4 site (h) and the unedited MYC locus (i) in WT and 2 G4 mutant clones. In h, the edited G4 site is highlighted by orange shading, and genes affected by the G4 mutation (j) are highlighted by blue shading. Loops were called using FitHiChIP at 10 kb resolution (q < 0.01). j Expression of selected genes near to the edited G4 site measured by RNA-seq