Fig. 3

Regions of differential chromatin accessibility are enriched for transcriptional regulators and pathways mirroring gene expression signatures. A TSS and PEREGRINE enhancer heatmap coverage plots of Tn5-accessible chromatin in NDC, APP^V717I, PSEN1^A79V, and PSEN2^N141I hiPSC-derived neurons as determined by ATAC-seq. B Differential accessibility plots (log₂FC) of ATAC-seq peaks for each FAD mutation relative to NDC (significant peaks: red, up; blue, down). C Annotation (promoter, PEREGRINE enhancer, or distal/intergenic) and directionality of significant differential ATAC-seq peaks for each FAD condition. D HINT TF footprinting analysis in all accessible ATAC-seq regions using the CIS-BP motif database to identify TFs with a change in footprinting activity. E Top differentially activated and repressed TFs across the FAD mutations based on HINT-ATAC footprinting analysis. F Tn5 insertion density in each FAD mutation relative to NDC around ASCL1 (top) or NRF1 (bottom) motifs as determined by HINT