Extended Data Fig. 3: ETS1 regulates the expression of tissue-destructive genes in SFs.
From: ETS1 governs pathological tissue-remodeling programs in disease-associated fibroblasts
a, Motif enrichment analysis in RANKL enhancers by HOMER software (P values: hypergeometric test) b, The expression levels of ETS family members in RA patients-derived SFs under the indicated conditions (NBDC accession code hum0207). Data were expressed as mean ± s.e.m. P values were determined by one-way ANOVA analysis followed by Turkey’s post hoc test. c, d, The expression levels of ETS1 in RA patient-derived SF sub-clusters F1 to F8 (c) and CIA SFs sub-clusters mFib1 to mFib4 (d). e, Regulatory target gene sets analysis in CIA SFs sub-clusters using MSigDB C3 datasets (legacy transcription factor targets) performed with VISION R package (P values: Wilcoxon rank-sum test). f, Alignment of the ETS1 variants associated with RA. The upper panel shows the P-values of the 29 variants within the ETS1 region (Chr. 11: 127,828,656-128,957,453 in hg19) which exceeded the genome-wide significance threshold (P < 5 × 10-8) in a previously performed RA GWAS study27. The dashed line indicates the genome-wide significance threshold (P < 5 × 10-8). The lower panel (from top to bottom) shows the H3K27ac ChIP–seq (GSE128642) peaks detected in RA patient SFs, candidate cis-regulatory element (cCRE) with promoter-like signatures (cCRE_PLS), cCRE with proximal enhancer-like signatures (cCRE_pELS), cCRE with distal enhancer-like signatures (cCRE_dELS), cCRE enriched with DNase and H3K4me3 signals (cCRE_DNase_H3K4me3) and cCRE enriched with CTCF signals (cCRE_CTCF). Overlapping of the RA-associated ETS1 variants with the H3K27ac ChIP–seq (GSE128642) peaks detected in RA patient SFs and the candidate cCRE are indicated. The red-colored dots (ChIP–seq) and blue-colored dots (cCRE) represent overlaps. The shaded area indicates the overlap among the RA-associated ETS1 variants, and the H3K27ac peaks detected in RA patient SFs and cCRE.
