Although all three of these proteins are upregulated in RCC, the reduction in H3K27me3 level implies that the H3K27 demethylases UTX and JMJD3 play more important roles than the H3K27 methyltransferase EZH2 in regulating p16INK4a expression. The gene discussed is CDKN2A; the disease is renal cell carcinoma.