Fig. 7: Transcription factors associated with inflammatory programming of proximal tubule cells.

a TF gene expression plotted against the TF score (mean of target gene and target CRE signature scores) highlights TFs enriched in healthy and injured/inflammatory PT cells. b Chromatin accessibility dynamics along the trajectory from healthy to inflammatory PT cells (Fig. 2f). Left panel: CREs linked to upregulated genes (L2FC > 0.1, adj. p-value < 0.05) clustered into modules with increased accessibility early, intermediate and late in the trajectory. Right panel: Smoothed graphs summarizing the mean accessibility for CREs in each module, with the percentage of injured and inflammatory PT cells above. c Proportions of CREs with putative binding sites for the respective TF family, grouped by module. d UMAP (Fig. 2a) of the AP-1 and NF-κβ1 TF score in PT cells. e TF footprint of JUN:FOS and RELA motifs in healthy, injured and inflammatory PT cells. f Left panel: intersection of chromosomal regions binding JUN or NF-κβ1 by CUT&RUN assay in renal proximal tubular cells (RPTECs) following TNF administration with differentially accessible chromatin in inflammatory PT cells. Right panel: Motif enrichment ratio in regions of intersection. g Chromatin profile and CUT&RUN signal tracks at archetypal inflammatory PT genes with AP-1 or NF-κβ1 target CREs. Upper tracks: The ATAC signal in healthy and injured/inflammatory PT cells. Lower track: The JUN or NF-κβ1 CUT&RUN peaks indicating the physical presence of the TF at genomic loci in TNF-treated RPTECs. h Visualisation of the predicted regulatory links between AP-1 or NF-κβ1 and selected genes upregulated in inflammatory PT cells (Fig. 2c). CREs are shown as diamonds (darker blue colour indicating increased accessibility) and target genes as circles (darker red colour indicating greater up-regulation). TF to CRE edges are coloured by the TF bound to the CRE.