Figure 2. Methylation-sensitive CTCF binding at ICRs organizes allele-specific chromatin architecture.
(A-B) Top: Pile-up density plots of cortex Capture Hi-C data generated by including 75 kb regions up- and downstream of each gDMR (A) and sDMR (B) separated by methylated vs unmethylated allele. Insulation score at DMR is shown in the bottom left corner of each plot. Bottom: Density plot of primary neuron CTCF tracks. (C) Volcano plot of paternally biased (blue) or maternally biased (red) CTCF binding peaks genome wide in mouse primary cortical neurons. (D-E) Top: Pile-up density plot of Capture Hi-C data from DMSO (D) or DNMTi-treated (E) mESCs across 75 kb regions up- and downstream of gDMRs separated by methylated vs unmethylated allele. Insulation score at DMR is shown in the bottom left corner of each plot. Bottom: Density plot of primary neuron CTCF tracks. n = 3 replicates per group. (F) Volcano plot of RNA-seq from DMSO vs DNMTi-treated mESCs illustrating changes in allelic expression ratio upon DNMTi treatment. padj is FDR corrected p-value of treatment x allele interaction. (G) Histone modification profiles from mouse brain on methylated vs unmethylated alleles across size-matched gDMR windows.