Fig. 4: Regulatory potential of DNMT3A CHIP-specific hypo-DMRs in IFN-γ response genes.

a Stacked bar plots showing the proportion of annotated hypo- and hyper-DMRs. In DMRs: proximal to the promoter, n = 1124; distal regulatory element, n = 423; others, n = 801. In randomly selected DMRs: proximal to the promoter, n = 314; distal regulatory element, n = 81; others, n = 1953. b Hi-C heatmap and other regulatory features for two example regions. Top, Hi-C contact maps (heatmap) for region 1 (RBPJ) and region 2 (CXCL2) with significant long-range chromatin interactions with the promoter regions and hypo-DMRs (arcs below the heatmap). Middle, distribution of hypo-DMRs and histone modification signals along Hi-C contact maps. Bottom, snapshots of interacting regions in the UCSC genome browser⁵⁸. Each DMR and promoter region are highlighted in yellow and blue, respectively. On the CpG island track, the color indicates the length of the islands: light green, smaller than 300 bases; cyan, larger than 300 bases. On the ENCODE cCRE track, the color indicates the type of signature of the DNA element: yellow, distal enhancer-like signature; orange, proximal enhancer-like signature; blue, promoter-like signature; purple, Dnase-H3K4me3 signature. For promoter regions, neither distal nor proximal enhancer signatures are shown in the figure. c Bar plots of combined scores relative to TNF-α for hypo-DMR linked genes and others for the same gene ontology library in Fig. 2c. Each point indicates a single-ligand perturbation term. The mean and standard error of the mean (SEM) of each gene set are presented in a bar plot. A one-sided Mann‒Whitney’s U test was performed (n.s.: nonsignificant, ^**P < 0.01).