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.

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Chakraborty AA, Nakamura E, Qi J, Creech A, Jaffe JD, Paulk J, Novak JS, Nagulapalli K, McBrayer SK, Cowley GS, Pineda J, Song J, Wang YE, Carr SA, Root DE, Signoretti S, Bradner JE, Kaelin WG Jr