Fig. 4

De novo DNA methylation during B cell differentiation. a Heat map of DNA methylation (DNAme) in lymph node B220⁺GL7⁻Fas⁻ naive B cells (nB), B220⁺PE⁺GL7⁺Fas⁺ germinal center B cells (GCB), and CD138⁺ bone marrow plasma cells (BMPC) in Dnmt3-sufficient (Dnmt3a^fl/flDnmt3b^fl/fl; C) and -deficient (Cd19^cre/+Dnmt3a^fl/flDnmt3b^fl/fl; KO) mice (left) and average DNA methylation (right). b Principle components analysis of DNAme. The percentage in parenthesis is the proportion of variation explained by each component. c Number of differentially methylated loci (DML) between nB, GC, and BMPC cell types. d Heat map of all DML identified in c. e Analysis of motifs enriched within 50 bp of DML. The false discovery rate (FDR) significance is denoted by color (key right) and a full list can be found in Supplementary Data 6. f Plot of DNA methylation levels proximal to all genomic binding motifs for the indicated factors. g Number of DML between Dnmt3-deficient mice in nB, GCB, and BMPC relative to Dnmt3-sufficient cell types. h Heat map of loci identified in g. i Average DNA methylation for all loci determined in f. j Overlap of Dnmt3 DML with H3K4me1⁺H3K27ac⁺ enhancers in the designated cell types (light orange: nB; orange: GCB, brown: BMPC). k Examples of differentially methylated loci between Dnmt3-sufficient and Dnmt3-deficient cells. Scale is from 0 to 100% DNAme. **P ≤ 0.01, ***P ≤ 0.001, Student's two-sided t-test. Data were derived from 3 experiments and 24 mice, where nB were isolated from 6 mice, GCB were from 12 mice (2 mice were pooled per sample), and BMPC were from 6 mice. Each cell type contained four female and two male (nB, GCB) or four male and two female (BMPC) mice split evenly between the genotypes