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Action of WDR5 and HDM2 inhibitors in SMARCB1-deficient cancer cells

ABSTRACT: Rhabdoid tumors (RT) are rare and aggressive pediatric tumors that are driven by the loss the tumor suppressor SNF5 (SMARCB1). Here we examine how RT cells respond to small molecule-mediated inhibitors of the “WIN” site of WDR5, a chromatin-associated protein that regulates a specific set of genes linked to protein synthesis. We characterize WDR5 binding in RT cell lines via ChIP-Seq and show that WIN site inhibitor rapidly and comprehensively displaces WDR5 from chromatin in these cells. Using Precision Run On-sequencing (PRO-Seq) we show that WDR5-bound protein synthesis genes are early and direct transcriptional targets of WIN site inhibitor. We also use RNA-Seq to characterize the persistent transcriptional changes in RT lines treated with WIN site inhibitor, and compare these transcriptional effects with those of the HDM2 inhibitor nutlin-3a.

ORGANISM(S): Homo sapiens

PROVIDER: GSE173207 | GEO | 2022/03/03

REPOSITORIES: GEO

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Synergistic Action of WDR5 and HDM2 inhibitors in SMARCB1-deficient cancer cells

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