(A) Representative contour plots and quantification showing Foxp3-YFP⁺ cells as frequency of splenic CD3ε⁺CD4⁺ cells from 8-week-old female Uhrf1^+/+ Foxp3^{YFP-Cre/YFP-Cre} (control) and Uhrf1^fl/flFoxp3^+/YFP-Cre (chimeric) mice (schematic). (B) CD25 heatmap overlaid on populations shown in A; associated graph quantifies CD25⁺ cells as percentages of splenic CD3ε⁺CD4⁺ cells. (C) MA plot comparing gene expression of splenic CD3ε⁺CD4⁺CD25^hiFoxp3-YFP⁺ cells from control mice (Uhrf1-sufficient cells) and Uhrf1 chimeric knockout mice (Uhrf1-deficient cells). (D) K-means clustering of differentially expressed genes scaled as Z score across rows. (E) Cumulative distribution function plot of 1.4 × 10⁶ well-observed CpGs expressed as β scores, with 0 representing unmethylated and 1 representing fully methylated; a shift in the cumulative distribution function up and to the left represents relative hypomethylation. (F) CpG methylation at the loci of differentially expressed genes (defined as the gene body ± 2 kb). (G) CpG methylation at 1335 DMRs. (H) Average gene expression at 567 gene loci near DMRs. n = 5 (control) and 12 (chimera) for A and B and 4 mice per group for C–H. Summary plots show all data points with mean and SD; violin plots show median and quartiles. *q < 0.05; **q < 0.01; ^†P < 0.001; ‡q or P < 0.0001; NS, not significant by Mann-Whitney U test (A and B), a mixed-effects analysis with the 2-stage linear step-up procedure of Benjamini, Krieger, and Yekutieli with Q = 5% (F), or Kolmogorov-Smirnov test for cumulative distributions (G and H); exact or asymptotic P and q values are in Supplemental Data. The asymptotic P value resulting from a Kolmogorov-Smirnov test for cumulative distributions is shown in E. See Supplemental Table 3 for fluorochrome abbreviations.