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Beschreibung

Histone-lysine N-methyltransferase, H3 lysine-79 specific (EC 2.1.1.43, UniProt Q8TEK3, also known as Disruptor of telomeric silencing-1 like, DOT1-like protein, H3-K79-HMTase, Histone H3-K79 methyltransferase, Lysine N-methyltransferase 4) is encoded by the DOT1L (also known as KIAA1814, KMT4) gene (Gene ID 84444) in human. Disruptor of telomeric silencing-1 like (DOT1L) catalyzes the mono-, di-, and tri-methylation of histone H3 on lysine-79 (H3K79). DOT1L-mediated H3K79 methylation is associated with active transcription. Accumulating evidences indicate a role of DOT1L and H3K79 in many biological processes, including DNA damage response, cell cycle, embryonic cell development, as well as the initiation and maintenance of mixed lineage leukemia (MLL)-rearranged leukemia. MLL fusion proteins such as AF9, AF10, and ENL recruit DOT1L to their target gene loci to help promote the transcription of genes that contribute to leukemic transformation of hematopoietic progenitor cells. DOT1L also has been identified as a coactivator of Wnt signaling in colorectal cancer, and is shown to induce neoplastic transformation of immortalized human breast epithelial cells and increase tumor initiation and growth of human breast cancer cells. In addtion, DOT1L is reported to regulate androgen receptor activity via direct methylation.