Fig. 2: The association of EZH2 with E2F1 is required for the noncanonical function.

a The enrichment profiles of EZH2 and H3K27me3 for EZH2⁺H3K27me3⁻ (noncanonical) and EZH2⁺H3K27me3⁺ (canonical) regions in HMEC and MDA-MB-231 cells, showing the read density for enrichment levels (top) and heat map (bottom) b Genome-wide distribution of EZH2 and H3K27me3 peaks for the EZH2⁺H3K27me3⁻ regions (top, noncanonical regions) and EZH2⁺H3K27me3⁺ (bottom, canonical regions). c Gene expression levels of canonical (n = 812) and noncanonical EZH2 target genes (n = 3,653). Gene expression levels in MDA-MB-231 cells were calculated in TPM from RNA-seq data. d A highly enriched transcription factor-binding motif identified by the motif analysis using noncanonical EZH2 target regions. e Transcription factors related to downregulated genes upon EZH2 knockdown (n = 1391). f The average enrichment patterns of EZH2, E2F1 and H3K27me3 for noncanonical (left) and canonical (right) regions centered at EZH2 peaks. g Colocalization of EZH2 and E2F1 and distribution of H3K27me3 at the CCNB1 and RRM2 locus. h The physical interaction between EZH2 and E2F1. i Domain organization of EZH2 and its truncated forms (top) and the physical interactions between ectopically expressed Flag–E2F1 in HEK293T cells and full-length and truncated forms of HA–EZH2 (bottom). j The physical interaction between E2F1 and PRC2 components. k A protein–protein interaction network of top 10% of proteins identified from EZH2 and E2F1 interactomes.