Extended Data Fig. 5: Redistribution of MYC on chromatin.

a. Heatmap of MYC occupancy analyzed by ChIP-Rx at 9,743 MYC promoters and 14,855 non-promoter sites in U2OS^MYC-Tet-On treated as indicated (HS: 42 °C for 30 min; DOX: 1 µg/ml, 24 h) followed by recovery for 30 min and 5 h (n = 2). b. Proportion of total called MACS2 peaks of indicated proteins which show reduced (loss) or increased (gain) occupancy after 4 h MG-132 treated for MYC in U2OS^MYC-Tet-On cells in absence or presence of DOX (CTL: n = 2; DOX: n = 3). c. Accumulation of JUN at 4,452 JUN-bound promoters documented by CUT&RUN. Average density plot of U2OS^MYC-Tet-On cells at indicated conditions (MG-132: 20 µM, 4 h; DOX: 1 µg/ml, 24 h) (n = 1). d. MYC ChIP qPCR of chromatin from U2OS^MYC-Tet-On cells documenting occupancy of MYC at the indicated promoters in control cells and exposure to DOX (1 µg/ml, 24 h), MG-132 (20 µM, 4 h), CBL0137 (5 µM, 5 h), or PlaB (1 µM, 4 h). Shown is mean of technical triplicates of one representative experiment of three biological replicates. e. Consensus motifs in non-promoter MYC binding sites using de-novo search algorithm (HOMER) at the 4,210 MYC binding sites non-promoters with increasing MYC levels and 6,644 promoter sites where MYC occupancy is reduced upon MG-132 (20 µM, 4 h) treatment (n = 2). f. Average density plot of MAX occupancy analyzed by CUT&RUN. MAX occupancy in U2OS^MYC-Tet-On cells upon treatment with DOX (1 µg/ml, 24 h) and MG-132 (20 µM, 4 h) at 6,644 promoter sites where MYC occupancy is reduced (left) and 4,210 non-promoter sites with increasing MYC occupancy (right) upon MG-132 treatment (n = 1). g. Venn diagram of results from co-localization studies using quantitative immunofluorescence considering proteins as colocalizing at a cut-off of PCC = 0.3. h. GO-term analysis of significantly (FDR < 0.05) enriched proteins upon MYC multimerization in APEX2 experiments (Fig. 2c). Hypergeometric p-values with correction for multiple testing using the gSCS algorithm in gprofiler2. i. Average density plot of SPT5 ChIP-Rx across genes at the 6,644 promoter sites where MYC occupancy is reduced upon MG-132 treatment in U2OS^MYC-Tet-On cells (MG-132: 20 µM, 4 h; DOX: 1 µg/ml, 24 h) (n = 2). In above panels, unless indicated otherwise, n indicates the number of independent biological replicates.