Fig. 3: DMR–peak–gene links define a multiomic signature of skin Treg cell development. | Nature Immunology

Fig. 3: DMR–peak–gene links define a multiomic signature of skin Treg cell development.

From: DNA hypomethylation traits define human regulatory T cells in cutaneous tissue and identify their blood recirculating counterparts

Fig. 3

a, Methylation, chromatin accessibility and expression of DMRs (left), differentially accessible peaks (middle) and differentially expressed genes (right) between skin Treg cells and blood CD45RA+ Treg cells (blood RA+ Treg cells). Rows represent genomic regions (left and middle) or genes (right). Columns indicate samples from individual donors (left and right) or mean accessibility across cells from a single donor (middle); n = 3 donors per cell type (methylation, Tissue Donors 7, 10 and 11 and Blood Donors 3–5), 2 donors per cell type (accessibility, ATAC Donors 1, 2, 4 and 5), 4 skin Treg donors and 5 blood CD45RA+ Treg donors (expression, Tissue Donors 7, 8, 10 and 11 and Blood Donors 3–5, 9 and 10). b, Correlation between differential methylation, accessibility and expression for DMR–peak–gene links (n = 1,203 DMR–peak–gene links). Positive values indicate larger methylation, accessibility or expression in skin Treg cells. Donors are as in a; FC, fold change. c, Smoothed methylation (top left), raw methylation (top right), chromatin accessibility (bottom left) and gene expression (bottom right; mean ± s.d.) in skin Treg and blood CD45RA+ Treg cells for selected DMR–peak–gene links. Highlighted regions mark DMRs (methylation tracks) and differential peaks (accessibility tracks). Vertical lines at the bottom of the methylation tracks mark CpG sites. Gene expression P values were determined by two-tailed Wald test implemented in DESeq2 (n = 4 skin donors and 5 blood donors) with a Benjamini–Hochberg correction. Donors are as in a. d, Enrichment of hallmark gene sets among genes belonging to the multiomic skin Treg cell signature. All gene sets displaying a Padj of <0.01 are shown. P values were determined by one-tailed Fisher’s exact test (n = 408 genes from the multiomic signature) with a Benjamini–Hochberg correction; DN, down; OR, odds ratio; r, Pearson correlation. Data are representative of two or more independent experiments with two or more individual donors.

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