Fig. 4: Repeats are derepressed in neurons in the absence of DNA methylation but not in the absence of the tested MBD proteins.

a, Percentage of reads (all repeats plus genes) mapping to all repeats or IAPs. Numbers of replicates (circles), WT (n = 2), MBD–QKO (n = 4, both clones combined), DNMT–TKO (n = 2). Multimapping reads counted in repeats (Methods). Bar plot shows the median of replicates. b, Expression change of repeat subfamilies in mutants over WT cell lines or tissue. Rows depict repeat subfamilies differentially expressed in MBD–QKO or DNMT–TKO neurons (RNA-seq, FDR ≤ 0.01 and |log2FC| ≥ 3, with a minimum of ten repeat instances; Extended Data Fig. 7a,b). Left, Ngn2 mouse ES cells (ES) or derived neurons (N). Right, public RNA expression data: ES_DNMT1_SETDB1, conditional deletion of SETDB1 and DNMT1 in ES cells74; Cortex_UHRF1, conditional deletion of Uhrf1 in cerebral cortex of postnatal day 5 mice61; E8.5_DNMT1, Dnmt1 mutant embryos at day 8.5 (ref. 68). Multimapping RNA-seq reads were considered (Methods). c, Representative gene (Gramd1c) activated in DNMT–TKO neurons by a transcribed IAP element (red arrowhead). Red line indicates splice junctions, illustrating that RNA reads derived from the IAP repeat overlap with the downstream exon. Chr16: 43970350−44073345.