Fig. 1

MYC inhibits the transcriptional program of mature luminal epithelial cells. a Western blot of c-MYC in IMEC WT and IMEC-MYC; β-ACTIN was used as loading control. Signal quantification is reported. Data are means ± SEM (n = 3). (**P < 0.01; Student’s t-test). b Phase contrast images of confluent IMEC WT and IMEC-MYC. Scale bar, 200 µm. c GSEA of mature luminal (ML) and luminal progenitor (LP) gene signatures in IMEC WT vs. IMEC-MYC (n = 3). d Heatmap showing the expression of luminal specifying TFs in IMEC WT and IMEC-MYC. e GSEA of genes regulated by enhancers bound by mature luminal-specific TFs in IMEC WT vs. IMEC-MYC (n = 3). f qRT-PCR of GATA3 and ESR1 in IMEC WT and IMEC-MYC, normalized on spike-in RNAs. Data are means ± SEM (n = 3). (**P < 0.01, ***P < 0.001; Student’s t-test). g ChIP-qPCR assessing MYC and MIZ1 binding and H3K4me3, H3K27ac, and H3K4me1 deposition at GATA3 promoter and ESR1 intronic enhancer in IMEC WT and IMEC-MYC. A scheme showing GATA3 and ESR1 PCR amplicons localization (red boxes) and layered H3K27ac signals from ENCODE is represented. Data are means ± SEM (n = 3). h Box plots representing the protein levels of GATA3 (left panel) and ESR1 (right panel) in breast cancer samples with unaltered or altered MYC level. i Scheme showing the MYC-induced reprogramming of IMEC WT to the luminal progenitor-like state of IMEC-MYC