The diverse functions of Dot1 and H3K79 methylation

被引:455
作者
Anh Tram Nguyen [1 ,2 ]
Zhang, Yi [1 ,2 ]
机构
[1] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA
[2] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA
关键词
chromatin; DOT1; epigenetics; histone; leukemia; transcription; HISTONE H3 LYSINE-79; CELL-CYCLE PROGRESSION; SACCHAROMYCES-CEREVISIAE; DNA-DAMAGE; TRANSCRIPTIONAL ELONGATION; MAMMALIAN-CELLS; NUCLEOSOME CORE; SET DOMAIN; METHYLTRANSFERASE DOT1; H2A PHOSPHORYLATION;
D O I
10.1101/gad.2057811
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
DOT1 (disruptor of telomeric silencing; also called Kmt4) was initially discovered in budding yeast in a genetic screen for genes whose deletion confers defects in telomeric silencing. Since the discovery similar to 10 years ago that Dot1 and its mammalian homolog, DOT1L (DOT1-Like), possess histone methyltransferase activity toward histone H3 Lys 79, great progress has been made in characterizing their enzymatic activities and the role of Dot1/DOT1L-mediated H3K79 methylation in transcriptional regulation, cell cycle regulation, and the DNA damage response. In addition, gene disruption in mice has revealed that mouse DOT1L plays an essential role in embryonic development, hematopoiesis, cardiac function, and the development of leukemia. The involvement of DOT1L enzymatic activity in leukemogenesis driven by a subset of MLL (mixed-lineage leukemia) fusion proteins raises the possibility of targeting DOT1L for therapeutic intervention.
引用
收藏
页码:1345 / 1358
页数:14
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