Nat. Rev. Nephrol. doi:10.1038/nrneph.2016.133 Figure 3 Malfunction of the epigenetic machinery contributes to genomic instability and deficiency of the DNA repair system in clear cell renal cell carcinoma (ccRCC) Figure 3 | Malfunction of the epigenetic machinery contributes to genomic instability and deficiency of the DNA repair system in clear cell renal cell carcinoma (ccRCC). Mutations in chromatin remodelling factors and histone modifying enzymes lead to abnormal changes in chromatin accessibility and the establishment of abnormal epigenetic patterns with functional consequences. Loss of histone marks H3K9me and H3K36me, which are associated with mutations in KDM5C and SETD2, respectively, results in unrestricted transcription of heterochromatic non-coding (nc)RNAs, and deficiency in the recruitment of mismatched repair (MMR) machinery to mutated regions. Similarly loss of ubiquitination H2K119Ub at loci undergoing DNA repair (associated with PBRM1 deficiency) leads to activation of gene expression from these damaged loci. These abnormalities contribute to genomic instability in ccRCC. DSB, double-strand break. Riazalhosseini, Y. & Lathrop, M. (2016) Precision medicine from the renal cancer genome Nat. Rev. Nephrol. doi:10.1038/nrneph.2016.133