Fig. 3: G4 presence in promoters is associated with bivalent and H3K4me3 promoter class transitions in differentiation.
From: G-quadruplex DNA structures in human stem cells and differentiation
a Schematic of H3K4me3, H3K27me3 and bivalent promoters and their associated transcriptional activity in stem cells. b Pie charts showing the proportion of promoters containing a G4 (G4 positive) in each promoter histone modification class: H3K4me3 (enrichment of H3K4me3 only), H3K27me3 (enrichment of H3K27me3 only), bivalent (overlap of H3K4me3 and H3K27me3 enrichments), other (non-overlapping H3K4me3 and H3K27me3 enrichments) and unmarked (negative for H3K4me3 and H3K27me3 enrichments). c Fold enrichment over random (n = 1000 permutations) of G4s in the promoter histone modification classes defined in b for each stem cell type. d Median normalised ChIP-seq hESC G4 signal density at hESC bivalent (top) and H3K4me3 (bottom) promoter regions. TSS transcription start site. e Distribution of histone modification transitions for bivalent and H3K4me3 hESC promoters after differentiation to CNCCs, segregated by G4 promoter types (Supplementary Fig. 9a, see Methods section): G4E+ G4D+ : G4 maintenance from hESCs to daughter cells; G4E+ G4D–: G4 present in hESCs and lost in daughter cells; G4E– G4D+ : G4 gained in daughter cell and G4E– G4D–: promoters lacking a G4 in both hESCs and daughter cells. f, g Median normalised H3K4me3 read density (f) and ATAC-seq signal (g) across hESC promoter subtypes as described in d. h Gene expression levels (log10[average TPM + 0.1], transcript per million averaged across biological replicates) for hESCs. Histone modification promoter classes as defined in b. Data are presented as median (centre) and interquartile range (box; the lower and upper bounds of the box represent the 25th and 75th percentiles, respectively). Whiskers represent ±1.5x interquartile range. N = 5, 3 and 4 biologically independent samples for hESCs, CNCCs and NSCs, respectively. Number of genes per group: ESC G4 positive (H3K4me3: 7827, bivalent: 3041, H3K27me3: 137 and unmarked: 400) and ESC G4 negative (H3K4me3: 3648, bivalent: 3309, H3K27me3: 1390 and unmarked: 38491). *p < 2E-16, one-sided Kolmogorov–Smirnov test.
