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The histone methyltransferase DOT1L: regulatory functions and a cancer therapy target.

ABSTRACT: DOT1L is a unique histone methyltransferase that targets the histone H3 lysine 79 (H3K79) residue for mono-, di- and tri- methylation. Histone H3K79 mono- and di-methylation results in active gene transcription, while H3K79 tri-methylation is associated with gene repression. DOT1L has a critical role in regulating gene transcription, development, cell cycle progression, somatic reprogramming and DNA damage repair. DOT1L interacts with Mixed Lineage Leukemia (MLL) fusion proteins, leading to enhanced H3K79 methylation, maintenance of open chromatin, overexpression of downstream oncogenes and leukemogenesis. Importantly, small molecule DOT1L inhibitors have been recently developed, and one of the DOT1L inhibitors is already under investigation in a Phase I clinical trial in patients with MLL fusion gene-driven leukemia.

SUBMITTER: Wong M

PROVIDER: S-EPMC4633909 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The histone methyltransferase DOT1L: regulatory functions and a cancer therapy target.

Wong Matthew M Polly Patsie P Liu Tao T

American journal of cancer research 20150815 9

DOT1L is a unique histone methyltransferase that targets the histone H3 lysine 79 (H3K79) residue for mono-, di- and tri- methylation. Histone H3K79 mono- and di-methylation results in active gene transcription, while H3K79 tri-methylation is associated with gene repression. DOT1L has a critical role in regulating gene transcription, development, cell cycle progression, somatic reprogramming and DNA damage repair. DOT1L interacts with Mixed Lineage Leukemia (MLL) fusion proteins, leading to enha ...[more]

PMID: 26609488

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Histone Methyltransferase DOT1L as a Promising Epigenetic Target for Treatment of Solid Tumors.

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Histone methyltransferase DOT1L controls state-specific identity during B cell differentiation

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