VHL and neoplasm: The resulting activation of HIF-1α and HIF-2α transcription factors causes the transcriptional upregulation of several histone demethylases including KDM3A, KDM4B, KDM5C and KDM6B6–10, implicating various alterations in the methylation of histone H3 as an early event in the process of tumour formation following VHL inactivation.