Fig. 2: Neurons lacking MBD or DNMT proteins display distinct transcriptional phenotypes.

a, ES cells carrying an inducible Ngn2 expression cassette can be rapidly differentiated towards neurons. Images represent morphology of WT, MBD–QKO and DNMT–TKO neurons 8 days after induction for at least three independent differentiation experiments. Scale bars, 50 µm. b, Gene expression changes between mutant and WT neurons; left, MBD–QKO; right, DNMT–TKO. Differentially expressed genes are depicted in blue or green (FDR ≤ 0.01 and |log₂FC| ≥ 1); genes that strongly gained expression in DNMT–TKO (FDR ≤ 0.01 and log₂FC > 3) are depicted in dark green (n = 434) and germline-specific genes Dazl and Asz1 in red. c,d, Average promoter methylation levels (c) and gene expression levels (d) in WT neurons of all expressed genes (total, n = 15,452) or of all genes differentially expressed in MBD–QKO and DNMT–TKO neurons (from b) or those shared between both conditions (shared: down n = 111, up n = 27). Black lines, median; boxes, first and third quartile; whiskers, maximum and minimum values of distribution after removal of outliers (Methods). e, Single-locus example of a germline-specific gene (Asz1) with a methylated promoter that is derepressed in the absence of DNA methylation (meth.) but not in the absence of MBD proteins. RPKM, reads per kilobase million.