DOT1L编码DOT1类的组蛋白H3K79甲基转移酶，对组蛋白3的79位赖氨酸残基进行甲基化。H3K79甲基化与双链断裂的DNA损伤反应有关。这种修饰涉及多种细胞和发育过程，包括细胞分裂、胚胎发育、减数分裂和造血。H3K79甲基化修饰染色质结构并可促进活性转录。在白血病中，这种修饰通过阻止抑制性Sirtuin1 (SIRT1)复合物的结合来促进活性转录。在混合谱系白血病（MLL）易位白血病中，DOT1L对MLL融合蛋白的转化活性很重要，并且DOT1L的抑制剂已被用于治疗这一亚群白血病。在乳腺癌中，DOT1L已证明与c-Myc-p300复合物协同作用以促进上皮至间质细胞转变，并且临床上与更具侵袭性的疾DOT1L病相关。在结肠癌、小细胞肺癌和鳞状头颈癌等实体瘤中均检测到DOT1L的突变。

DOT1L encodes for DOT1-like histone H3K79 methyltransferase, methylating the histone 3 lysine 79 residue. H3K79 methylation is associated with DNA damage response to double stranded breaks. This modification has also been implicated in diverse cellular and developmental processes including cell division, embryonic development, meiosis, and hematopoiesis. H3K79 methylation modifies chromatin structure and can promote active transcription. In leukemias, this modification promotes active transcription by preventing the binding of the inhibitory Sirtuin1 (SIRT1) complex. In Mixed lineage leukemia (MLL) translocation leukemias, DOT1L was shown to be important for the transformation activity of the MLL fusion protein, and inhibitors of DOT1L have been employed in the treatment of this subset of leukemias. In breast cancer, DOT1L has been shown to cooperate with a c-Myc-p300 complex to promote epithelial to mesechymal transition and clinically be associated with more aggressive disease. Mutations in DOT1L have been identified in large-scale sequencing efforts of solid tumors including colon, small cell lung cancer, and squamous head and neck cancer.

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