The emerging role of DOT1L in cell proliferation and differentiation: Friend or foe

Cell proliferation and differentiation are the basic physiological activities of cells. Mistakes in these processes may affect cell survival, or cause cell cycle dysregulation, such as tumorigenesis, birth defects and degenerative diseases. In recent years, it has been found that histone methyltransferase DOT1L is the only H3 lysine 79 methyltransferase, which plays an important role in the process of cell fate determination through monomethylation, dimethylation and trimethylation of H3K79. DOT1L has a pro-proliferative effect in leukemia cells; however, loss of heart-specific DOT1L leads to increased proliferation of cardiac tissue. Additionally, DOT1L has carcinogenic or tumor suppressive effects in different neoplasms. At present, some DOT1L inhibitors for the treatment of MLL-driven leukemia have achieved promising results in clinical trials, but completely blocking DOT1L will also bring some side effects. Thus, this uncertainty suggests that DOT1L has a unique function in cell physiology. In this review, we summarize the primary findings of DOT1L in regulating cell proliferation and differentiation. Correlations between DOT1L and cell fate specification might suggest DOT1L as a therapeutic target for diseases.