VHL and nonpapillary renal cell carcinoma: In clear cell renal cell carcinoma (CCRCC) VHL-defective RCC4 and RCC10 cells, binding of HIF-1α/2α to the reverse HRE (rHRE) on the HIF1A promoter, leads to H3K9 methylation, H3K4 de-methylation and HIF1A repression55.