Extended Data Fig. 7: Loss of Menin alleviates repression of bivalent genes.
From: Targeting Menin disrupts the KMT2A/B and polycomb balance to paradoxically activate bivalent genes
a, Volcano plot showing log2FC gene expression from RNA-seq data in K-562 cells expressing MEN1 sgRNA compared with control sgRNA. Selected MHC class I genes are labelled. Two-sided Wald test; P values adjusted for multiple testing. b, Venn diagram depicting overlap in genes downregulated (Padj < 0.05 and fold change > 2) after CRISPR deletion of MEN1, PSIP1 or EED. c, Venn diagrams depicting overlap in genes up- and downregulated (Padj < 0.05 and fold change > 2) after CRISPR deletion of MEN1 or PSIP1, or 500 nM VTP50469 treatment. d, Pharmacological inhibition of Menin–KMT2A/B induces genome-wide displacement of Menin from chromatin. Menin ChIP–seq in K-562 cells treated for 48 h with DMSO or 1 µM VTP50469. Average profile plots (top) and heatmaps (bottom) of Menin-occupied sites −3kb TSS/+3 kb TES. Genomic regions are ordered by Menin occupancy in the control sample. e,f, Immunoblots of K-562 Cas9 (control), MEN1-KO, PSIP1-KO and PCGF1-KO cells. g, Genomic snapshots of MHC-I genes from SUZ12 ChIP–seq data in K-562 Cas9 control and MEN1-KO cells. h, Genomic snapshots of H3K4me3, SUZ12 ChIP–seq and H3K27me3 CUT&Tag in K-562 Cas9 control and MEN1-KO cells.
