DOT1L (Disruptor of Telomeric silencing 1-like, also known as KMT4) is the mammalian homologue of the yeast Dot1 protein and the Drosophila Grappa protein. DOTL1 is the enzyme responsible for lysine 79 methylation of histone H3. DOT1L can promote an oncogenic pattern of gene expression through binding with several MLL fusion partners found in acute leukemia, thus leading to aberrant methylation of lysine 79 at MLL target genes. In contrast to most other histone lysine methyltransferases, DOT1L does not contain a SET domain. Biochemical studies suggest that recombinant DOT1L is active on recombinant nucleosomes.
