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Background：
Histone H3 forms H3-H4 tetramers as nucleosome core scaffold. Lysine methylation is a key reversible epigenetic modification regulated by methyltransferases and demethylases. Methylation recruits distinct reader proteins to control chromatin state, transcription elongation, DNA damage repair and genome stability. Different lysine methylation sites on H3 possess unique biological roles. H3 Lys79 is located on the outer surface of H3 globular core domain. H3K79 monomethylation (H3K79me1) is mainly catalyzed by DOT1L methyltransferase, enriched across the coding regions of actively transcribed genes. This modification promotes RNA polymerase II elongation and participates in resolving transcription-replication conflicts. Meanwhile, H3K79me1 accumulates at DNA double-strand break foci to initiate damage checkpoint response. Abnormal DOT1L activity and disrupted H3K79me1 level are closely associated with leukemia and solid tumor progression.
