Dpy30 regulates Myc binding to targets and Myc-driven tumorigenesis (Illumina HumanHT-12 V4.0 expression). Homo sapiens

It remains unclear how epigenetic modulators impact the tumorigenic potential of Myc. Here we show that the core subunits, including Dpy30, of the major H3K4 methyltransferase complexes are selectively upregulated in Burkitt lymphoma, and Dpy30 is important for efficient genomic binding of Myc. Dpy30 heterozygosity does not affect normal animal physiology, but significantly suppressed lymphomagenesis and reduced expression of a subset of key pro-survival genes when Myc is hyper-activated. Dpy30 heterozygosity also impedes cellular transformation without affecting normal cell growth. These results suggest that Myc hijacks this chromatin modulator to coordinate its oncogenic program for efficient tumorigenesis, meanwhile creating “epigenetic vulnerability”, which we then exploited by specifically targeting Dpy30’s activity to inhibit growth of the Burkitt lymphoma cell model. Overall design: Control and Dpy30 KD P493-6 cells were treated with tetracycline for 3 days (to turn off Myc). Tetracycline was thoroughly washed and cells were incubated in Tet-free medium for 4 hours. RNAs from cells before Tet treatment, after Tet treatment and right before washing Tet away, and 4h after washing Tet away, were subjected to Illumina microarray analyses.