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Dpy30 regulates Myc binding to targets and Myc-driven tumorigenesis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE101854 | GEO | 2018/08/01

REPOSITORIES: GEO

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Dpy30 regulates Myc binding to targets and Myc-driven tumorigenesis (ChIP-seq, RNA-seq)

Project description: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.

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