Extended Data Fig. 9: The contribution of TEs to the epigenetic landscape of skin T_reg cells and blood CCR8⁺ T_reg cells.

a, b, Enrichment of TE classes (left) and subfamilies (right) in regions hypomethylated (a) or hyperaccessible (b) in blood CD45RA⁺ T_reg cells. P values: one-tailed permutation test assessing enrichment of TE insertion sites among DMRs or peaks (see Methods) based on 1,742 DMRs (a) and 5,722 differential peaks (b) displayed in Fig. 3 with Benjamini-Hochberg correction. c, Left, Chromatin accessibility of peaks overlapping with annotated LTR-TE, DNA-TE and SINE insertion sites (n = 2 donors per cell type). White horizontal lines inside violins indicate medians across all peaks. Right, Distribution of differences in mean accessibility (across the two donors) between skin T_reg cells and blood CD45RA⁺ T_reg cells for each peak. Numbers indicate how many insertion sites displayed differences below and above 0. d, Left, Methylation of annotated LTR, DNA-TE and SINE insertion sites as in c with skin T_reg, fat T_reg and blood CD45RA⁺ T_reg (n = 3 donors per cell type). White horizontal lines inside violins indicate medians across all insertion sites. Right, Distribution of differences in mean methylation (across the three donors) between any two cell types for each insertion site. Numbers indicate how many insertion sites displayed differences below and above 0. e, Smoothed methylation and chromatin accessibility around selected TE insertion sites. Highlighted regions mark DMRs (methylation tracks), differential peaks (accessibility tracks) and TE insertion sites overlapping with DMRs (only TE subfamilies enriched among the DMRs; gene tracks). Vertical lines at the bottom of the methylation tracks mark CpG sites (CpG sites overlapping with TEs are shown in red). TE labels correspond to TE subfamilies. Parts of these plots are duplicated from Fig. 3 and Extended Data Fig. 3 as they show the same genomic regions. f, Top, Chromatin accessibility of peaks displaying hyperaccessibility in skin T_reg cells and overlapping with DNA-TE, LINE, LTR-TE and SINE insertion sites (n = 2 donors per cell type). White horizontal lines inside violins indicate medians across all peaks. Bottom, Distribution of differences in mean accessibility (across the two donors) between any two cell types for each peak. Numbers indicate how peaks displayed differences below and above 0. Data are representative of two or more independent experiments with two or more individual donors.