Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Other
Summary
We discovered potent small molecule inhibitors against the WIN site of WDR5. These inhibitors selectively block the proliferation of mammalian cells carrying fusions of the MLL1 oncogene. Here, we show that these inhibitors result in the rapid displacement of WDR5 from chromatin in both sensitive (MV4:11) and non-sensitive (K562) cell lines, induce early changes in the distribution of active polymerases at a subset of WDR5-bound genes, and induce global transcript changes that are consistent with induction of the tumor suppressor p53.
Overall design
MV4:11 or K562 cells were treated with one of two WIN site inhibitors (C3 or C6), a negative control compound (C6nc), or DMSO. ChIP-Seq was used to track interaction of WDR5 with chromatin; PRO-Seq was used to track early changes in the distribution of active RNA polymerases, and RNA-Seq was used to monitor long-term transcriptional changes. RNA-Seq was also performed on MV4:11 cells treated with the HDM2 inhibitor nultin.
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