A number of oncogenic histone point mutations have been identified across a host of cancer studies. We report that the H3.3 G34R (glycine to arginine) substitution mutation found in paediatric gliomas, causes widespread changes in H3K9me3 and H3K36me3 by interfering with the Kdm4 family of K9/K36 demethylases. Expression of a targeted single-copy of H3.3 G34R was sufficient to induce chromatin alterations which genocopied a Kdm4 a/b/c triple-knockout. In vitro and in vivo immunoprecipitation assays demonstrated that the H3.3 G34R mutant binds Kdm4 with high affinity while simultaneously inhibiting enzymatic activity. These studies show that H3.3 G34R acts in a dominant negative fashion by inhibiting Kdm4, triggering genome-wide alterations to promote oncogenesis. We propose a general model where oncogenic histone mutations alter the genome through interactions with epigenetic erasers, writers and readers.