Deregulation of HIF-Responsive Demethylases Causes Synthetic Lethality Between the VHL Tumor Suppressor Gene and the EZH1 Histone Methyltransferase

Comparison of ccRCC cells with high HIF or low HIF activity Overall design: Cells expressing control (VEC) were compared to cells with ARNT1 loss using sh/sgRNA targeting ARNT1 The samples labeled 'con' are parental Vhl-null cells and represent the 'high HIF' state. The other 2 cell lines represent the 'low HIF' state. The cell line labeled shArnt have loss of a protein named ARNT by virtue of RNAi-mediated knockdown using a shRNA targeting ARNT. The sample labeled lcARNT has loss of ARNT protein using a lenti-crispr mediated sgRNA.