Fig. 3: AIRE may predominately contribute to transcript mis-initiation.
From: Transcriptomic diversity in human medullary thymic epithelial cells
A Log2 odds ratio (OR) point estimate for transcription factor motifs enriched (p ≤ 0.05 by Fisher's exact test after Bonferroni correction) within 200 bp of either mTEChi- or mTEClo-specific TSRs. OR values greater than 0 represent increased use surrounding mTEChi-specific TSRs; color-coded by population with increased odds. B Of those known transcription factor motifs enriched around mTEChi- or mTEClo-specific TSRs (A), only six genes were found to be differentially expressed (Wald test, Benjamini–Hochberg adjusted q ≤ 0.05) by RNA sequencing. Only 3 of these 6 transcripts (indicated by an asterisk) were enriched in the mTEC population expected from the motif enrichment around the TSRs. C Distance in kilobases (kb) to nearest known super enhancer or D typical enhancer in SEdb59. E mTEChi-specific TSRs were more commonly located outside of known promoter regions for AIRE-induced genes, but not for FEZF2-induced genes. TRAs not induced by either AIRE or FEZF2 and housekeeping genes also show mTEChi-specific TSRs enriched outside promoters. F Distribution of transcript-level expression values in mTEChi cells demonstrates a higher average expression of FEZF2-induced genes relative to AIRE-induced genes. TPM transcripts per million. G Mouse Chromatin ImmunoPrecipitation sequencing (ChIP-Seq) data (n = 4)24 demonstrates higher mean (central line) counts per million mapped reads (CPM) of H3K4me3 (histone marker of transcriptional activation, top) for FEZF2 genes. Conversely, higher CPM of H3K27me3 (transcriptional repression, bottom) was observed for AIRE-induced genes. Error bars or bands show either 95% confidence intervals (A, G) or standard deviation (E); boxplots show median (central line) with interquartile range (IQR, box) and extrema (whiskers at 1.5× IQR). Outliers beyond 1.5× IQR are shown as dots (C, D, G). Values above horizontal bars indicate p values derived by the two-sided Mann–Whitney U test (C, D, F) or by the two-sided paired t-test (E). A–F: n = 5 paired mTEC samples. Source data for A–F are provided in the Source Data file.
