Fig. 4: EZH2 and KDM2B co-occupies and negatively regulate the expression of Cip/Kip2 protein CDKN1C.

A Co-occupied peaks of KDM2B and EZH2 in Z138 cells (within 2KB of TSS. B Enriched pathways analysis using Enrichr for the co-occupied 1950 peaks from panel A showing enrichment of cell cycle pathways. C Cell cycle-related loci (129) were functionally distinguished using enricher to identify 14 genes with functional relation to G1/S transition, including CDKN1C. D Genomic browser (hg19) for enrichment KDM2B and EZH2 on the target CDKN1C Loci with an overlay of ATAC in Z138 cells. E Heatmap showing Relative Densitometric Unit (RDU) calculated from Western Blot expression of FGFR1, KDM2B, EZH2, and CDKN1C in FGFR1 high vs. low MCL patient samples. F Western blot depicting CDKN1C increase in expression upon tazemetostat and valemetostat treatment in Z-138, Jeko-1R, and SP-49R cells. Veh: vehicle control. G Western blots to show CDKN1C expression in Z-138, Granta-519, Jeko-1R, and SP-49R control vs. shFGFR1 cells. H Western blots to show EZH2 expression in Z-138, Granta-519, Jeko-1R, and SP-49R cells upon erdafitinib treatment. I Percent increase in G1 cell percentage in Z-138 and (J) Granta-519 cells upon transfection with scrambled si-RNA (control) and si-CDKN1C and subsequent treatment with erdafitinib. 2-way ANOVA (a = 0.05).