Evaluating whether neurons, B cells, and T cells show preferential disruption of chromatin accessibility at the same regulatory elements in Kabuki syndrome (KS) types 1 and 2. (A–H) P-value distributions from mutant (KS1 or KS2) versus wild-type differential accessibility analyses in either neurons or T cells. Shown both for ATAC peaks genome-wide and for promoters only. The red densities correspond to ATAC peaks overlapping peaks disrupted in B cells (Q-value < 0.1), whereas the blue densities correspond to ATAC peaks overlapping peaks not disrupted (but present) in B cells. (I) The ratio (y-axis) of the proportion of ATAC peaks that overlap differentially accessible peaks in B cells and are also differentially accessible in either neurons (orange dots/squares) or T cells (black dots/squares) over the average proportion of ATAC peaks that overlap randomly sampled B cell peaks and are also differentially accessible in either neurons or T cells. The ratio is computed starting either with B cell peaks more compact in mutants (dots) or with B cell peaks more open in mutants (squares). Only squares are depicted for KS2 promoters, because there are too few B cell promoter peaks that are significantly more compact in mutants (17 peaks; see also Results) to do a meaningful analysis. The dashed horizontal line at one corresponds to the null expectation when there is no significant overlap between the ATAC peaks with disrupted chromatin accessibility in the two cell types tested. (J) The percentage of differentially accessible ATAC peaks in neurons (1 − π0; Methods), among ATAC peaks that are specific to neurons (gray bars) or ATAC peaks that overlap peaks that are also present in B or T cells (pink bars).
