Histone-lysine N-methyltransferase, H3 lysine-79 specific (DOT1L)

Histone-lysine N-methyltransferase, H3 lysine-79 specific (DOT1L) is a highly conserved enzyme that catalyzes mono-, di-, and tri-methylation of lysine 79 on histone H3, a key epigenetic mark regulating chromatin state and gene transcription. Unlike other histone methyltransferases, DOT1L lacks a SET domain and instead utilizes an Adomet-binding motif for transfer of methyl groups from S-adenosyl methionine. DOT1L is critically involved in embryonic development, genomic stability, cell cycle progression, transcriptional regulation, DNA repair, and immune modulation. DOT1L aberrations are implicated in leukemias (especially MLL-rearranged forms) and aggressive solid tumors; it functions both as promoter and suppressor of gene expression according to cellular context. DOT1L represents a novel therapeutic target for epigenetic cancer therapy, with selective inhibitors being clinically investigated, though selectivity and safety remain major challenges[1][2][3][4][5][6][7][8].

Other names

DOT1-like proteinDOT1KMT4KIAA1814Histone H3-K79 methyltransferaseH3-K79-HMTaseLysine N-methyltransferase 4NDNS

Inhibition of H3K79 methylation Modulation of gene expression via epigenetic blockade Suppression of oncogenic gene transcription, especially *HOXA9* and *HOXA7* in MLLr leukemia[1][4]