Extended Data Fig. 3: Acute transcriptional consequences of MED14 degradation in HCT-116 cells.
From: Selective Mediator dependence of cell-type-specifying transcription
a, CellTiter-Glo viability-based 72 h dose-response of dTAG7 and dTAGV-1 in HCT-116 MED14-dTAG cells. Mean±s.d. of n = 3 drug treatments. b, Time-resolved immunoblot of MED14-dTAG degradation. c, Differences in TT-seq nascent transcript levels (n = 2 independent treatments). Significantly deregulated (DESeq2 q < 0.01; dark grey), SE-proximal (blue), and auto-regulatory TF genes (red) are highlighted. Dark grey line: median log2 fold change of all n = 21,629 transcription units. d, TT-seq signal of two auto-regulatory TFs, and an expression-matched control gene. H3K27ac and H3K4me3 ChIP-seq signals are from publically available data (GSE72622; see Supplementary Table 7)85. e, Fold-change (color) and significance (size) of SE-driven HCT-116 cell identity and expression-matched control gene sets (data as in c). f, Regulatory wiring of 17 auto-regulatory TFs in the HCT-116 cell type-specifying gene regulatory network. Arrows: the given TF has binding motifs in the target TF’s SE region(s). Edge weight mirrors number of motifs. g, Overlap of KBM7 and HCT-116 auto-regulatory TFs. h, Cell type-specific impact of 1 h MED14 degradation. Auto-regulatory TFs in KBM7 (blue, for example MYB), HCT-116 (orange, for example TGIF1), or MYC (black) as the only shared TF are highlighted. Colored lines: median log2FC in the respective cell line. i, Mean steady state expression of auto-regulatory TFs in merged 1 h and 2 h DMSO TT-seq conditions and transcriptional defects after 1 h MED14 degradation. Unprocessed western blot shown in Source Data.
