fig5

Figure 5. MUC1-C→E2F1 pathway intersects induction of PcG and TrxG complexes. A. The PcG/PRC2 components EZH2, SUZ12, and EED are activated by MUC1-C/E2F complexes. The binding of MUC1-C to EZH2 induces H3K27 trimethylation with the repression of CDH1 and other TSGs. MUC1-C→E2F1 signaling also activates the TrxG SWI/SNF (BAF, PBAF) chromatin remodeling complexes. MUC1-C associates with nuclear (i) BAF in inducing the NANOG pluripotency factor and the NOTCH1 stemness gene, and (ii) PBAF in activating NRF2 target genes that regulate redox balance. In doing so, MUC1-C→E2F1 signaling has the capacity to fine-tune the intersection of PcG and TrxG proteins in driving the CSC state. B. Formation of MUC1-C complexes with BAF and PBAF on specific target genes, such as NANOG (BioRender), has been detailed in recent publications^[52,56,57]. CSC: Cancer stem cell.