Extended Data Fig. 4: The chromatin accessibility landscape in neurons changes in response to loss of DNA methylation but not MBD proteins.

a, Unsupervised clustering of ATAC-seq samples from WT and mutant neuron cells. Colors indicate pairwise Pearson’s correlation coefficients (PCC) of log-transformed normalized read counts in ATAC-seq peaks, indicating clear separation of DNMT-TKO from WT and MBD-QKO ES cells. b, MA plot showing mean chromatin accessibility (ATAC-seq) versus accessibility changes for neurons lacking MBD proteins or DNA methylation compared to WT. For differential accessibility analysis all replicates from both MBD-QKO clones were combined. Sites with an |log2FC| > 1 compared to WT and FDR < 0.01 are colored. c, Percent TSS-proximal ATAC-seq peaks (<1000 bp, left plot) or peaks overlapping with CpG islands (right plot) from b that do not change in any condition (unchanged, n = ~83,000), or change accessibility in DNMT-TKO (up, n = 7121 or down, n = 5606) or MBD-QKO neurons (up, n = 126 or down, n = 97). d, same as in c for ATAC-seq peak width or e, ATAC-seq peak methylation levels. Boxplots as in Fig. 2d. f, Expression change of genes closest to peaks that are unchanged between conditions or peaks that gain (up) or lose accessibility (down) in DNMT-TKO neurons binned by distance to TSS. Number of peaks per bin is indicated. Boxplots as in Fig. 2d.