Collectively, loss of SETD2-mediated H3K36me3 is associated with increased chromatin recruitment of histone chaperones ASF1A/B, enhanced histone exchange, and increased H3K56ac deposition in both kidney and lung cancers, all of which is analogous to the findings observed in Set2-deficient yeast (6, 39, 40). Here, SETD2 is linked to lung cancer.