DOT1L

DOT1L
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1NW3, 2MV7, 3QOW, 3QOX, 3SR4, 3SX0, 3UWP, 4EK9, 4EKG, 4EKI, 4EQZ, 4ER0, 4ER3, 4ER5, 4ER6, 4ER7, 4HRA, 4WVL, 5DSX, 5JUW, 5DRT, 5DTM, 5DTQ, 5DT2, 5DRY, 5DTR
Identifiers
Aliases	DOT1L, DOT1, KMT4, DOT1 like histone lysine methyltransferase
External IDs	MGI: 2143886 HomoloGene: 32779 GeneCards: DOT1L
Genetically Related Diseases
osteoarthritis/osteodystrophy[1]
Gene ontology Molecular function • methyltransferase activity • transferase activity • DNA binding • histone methyltransferase activity (H3-K79 specific) • transcription factor binding • protein binding • histone methyltransferase activity • histone-lysine N-methyltransferase activity Cellular component • nucleoplasm • nucleus • protein complex Biological process • telomere organization • methylation • chromatin silencing • regulation of transcription regulatory region DNA binding • regulation of cell cycle • regulation of JAK-STAT cascade • positive regulation of transcription from RNA polymerase II promoter • positive regulation of cell proliferation • covalent chromatin modification • histone H3-K79 methylation Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	84444	208266
Ensembl	ENSG00000104885	ENSMUSG00000061589
UniProt	Q8TEK3	n/a
RefSeq (mRNA)	NM_032482	NM_199322
RefSeq (protein)	NP_115871.1	n/a
Location (UCSC)	Chr 19: 2.16 – 2.23 Mb	Chr 10: 80.76 – 80.8 Mb
PubMed search	[2]	[3]
Wikidata

View/Edit Human

View/Edit Mouse

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.^[4][5] 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".^[6]

DOT1L has been reported to play an important role in the processes of mixed-lineage leukemia (MLL)-rearranged leukemias^[7]

Small molecule inhibitors of Dot1L catalytic activity have been developed.^[8][9]

References

1. "Diseases that are genetically associated with DOT1L view/edit references on wikidata".
2. "Human PubMed Reference:".
3. "Mouse PubMed Reference:".
4. "Entrez Gene: DOT1L DOT1-like, histone H3 methyltransferase (S. cerevisiae)".
5. Vlaming, H., & van Leeuwen, F. (2016). The upstreams and downstreams of H3K79 methylation by DOT1L. Chromosoma, 1-13. doi:10.1007/s00412-015-0570-5
6. Soria-Valles, C., Osorio, F. G., & López-Otín, C. (2015). Reprogramming aging through DOT1L inhibition. Cell Cycle, 14(21), 3345-3346. doi:10.1080/15384101.2015.1093443
7. Slany RK (2016). "The molecular mechanics of mixed lineage leukemia". Oncogene. doi:10.1038/onc.2016.30. PMID 26923329.
8. 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.
9. 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.