DOT1L

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

DOT1-like (Disruptor of telomeric silencing 1-like), histone H3K79 methyltransferase (S. cerevisiae), also known as DOT1L, is a protein found in humans, as well as other eukaryotes.[1][2] The methylation of histone H3 lysine 79 (H3K79) by DOT1L which is a conserved epigenetic mark in many eukaryotic epigenomes, increases progressively along the aging process, suggesting that "DOT1L might function as a vital clock, ticking the hours impassively".[3]

DOT1L has been reported to play an important role in the processes of mixed-lineage leukemia (MLL)-rearranged leukemias[4]

Small molecule inhibitors of Dot1L catalytic activity have been developed.[5][6]

References

  1. ↑ "Entrez Gene: DOT1L DOT1-like, histone H3 methyltransferase (S. cerevisiae)".
  2. ↑ Vlaming H, van Leeuwen F (2016). "The upstreams and downstreams of H3K79 methylation by DOT1L". Chromosoma. 125: 1–13. doi:10.1007/s00412-015-0570-5.
  3. ↑ Soria-Valles C, Osorio FG, López-Otín C (2015). "Reprogramming aging through DOT1L inhibition". Cell Cycle. 14 (21): 3345–3346. doi:10.1080/15384101.2015.1093443. PMC 4825545.
  4. ↑ Slany RK (2016). "The molecular mechanics of mixed lineage leukemia". Oncogene. doi:10.1038/onc.2016.30. PMID 26923329.
  5. ↑ Yao Y, Chen P, Diao J, Cheng G, Deng L, Anglin JL, Prasad BV, Song Y (2011). "Selective inhibitors of histone methyltransferase DOT1L: design, synthesis, and crystallographic studies". Journal of the American Chemical Society. 133 (42): 16746–9. doi:10.1021/ja206312b. PMC 3492951. PMID 21936531.
  6. ↑ Chen S, Li L, Chen Y, Hu J, Liu J, Liu YC, Liu R, Zhang Y, Meng F, Zhu K, Lu J, Zheng M, Chen K, Zhang J, Jiang H, Yao Z, Luo C (2016). "Identification of Novel Disruptor of Telomeric Silencing 1-like (DOT1L) Inhibitors through Structure-Based Virtual Screening and Biological Assays". Journal of Chemical Information and Modeling. 56 (3): 527–34. doi:10.1021/acs.jcim.5b00738. PMID 26914852.

Further reading

  • Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O (April 2001). "Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 8 (2): 85–95. doi:10.1093/dnares/8.2.85. PMID 11347906.
  • Feng Q, Wang H, Ng HH, Erdjument-Bromage H, Tempst P, Struhl K, Zhang Y (June 2002). "Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain". Current Biology. 12 (12): 1052–8. doi:10.1016/S0960-9822(02)00901-6. PMID 12123582.
  • Min J, Feng Q, Li Z, Zhang Y, Xu RM (March 2003). "Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase". Cell. 112 (5): 711–23. doi:10.1016/S0092-8674(03)00114-4. PMID 12628190.
  • Jikuya H, Takano J, Kikuno R, Hirosawa M, Nagase T, Nomura N, Ohara O (February 2003). "Characterization of long cDNA clones from human adult spleen. II. The complete sequences of 81 cDNA clones". DNA Research. 10 (1): 49–57. doi:10.1093/dnares/10.1.49. PMID 12693554.
  • Okada Y, Feng Q, Lin Y, Jiang Q, Li Y, Coffield VM, Su L, Xu G, Zhang Y (April 2005). "hDOT1L links histone methylation to leukemogenesis". Cell. 121 (2): 167–78. doi:10.1016/j.cell.2005.02.020. PMID 15851025.
  • Sistayanarain A, Tsuneyama K, Zheng H, Takahashi H, Nomoto K, Cheng C, Murai Y, Tanaka A, Takano Y (2006). "Expression of Aurora-B kinase and phosphorylated histone H3 in hepatocellular carcinoma". Anticancer Research. 26 (5A): 3585–93. PMID 17094487.


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