Property Summary

NCBI Gene PubMed Count 56
PubMed Score 182.28
PubTator Score 102.68

Knowledge Summary


No data available


  Disease (4)


  Differential Expression (7)

Disease log2 FC p
ependymoma 1.200 2.0e-02
osteosarcoma -1.264 7.3e-05
medulloblastoma 1.800 1.0e-05
atypical teratoid / rhabdoid tumor 1.800 2.0e-04
glioblastoma 1.400 3.3e-04
medulloblastoma, large-cell 1.600 2.9e-04
primitive neuroectodermal tumor 1.500 3.9e-04

 IMPC Phenotype (1)

Gene RIF (43)

27002147 these findings strongly support the contention that histone methyltransferase, DOT1L-associated epigenetic changes induced by HA play pivotal roles in miR-10 production leading to up-regulation of RhoGTPase and survival proteins.
26927674 MLL1 and DOT1L cooperate with meningioma-1 to induce acute myeloid leukemia.
26830124 These data converge on a possible mechanism for hDot1L stimulation in which histone H2B physically 'corrals' the enzyme into a productive binding orientation.
26439302 The PZP domain of AF10 senses unmodified H3K27 to regulate DOT1L-mediated methylation of H3K79.
26385168 Report drug formulation/delivery of DOT1L inhibitor pinometostat in leukemia.
26240340 analysis of a functional hotspot on ubiquitin that is required for the stimulation of human Dot1
26199140 expression associated with poorer survival and aggressiveness of breast cancers
26118503 Targeting DOT1L and HOX gene expression in MLL-rearranged leukemia and beyond.
25921540 The graded reduction of the DOT1L interaction with MLL-AF9 results in differential loss of H3K79me2 and me3 at MLL-AF9 target genes.
25576241 Three candidate variants were identified: p.Glu1313Lys in Insulin receptor (INSR), p.Arg81Pro in F-box protein 24 (FBXO24) and p.Pro1146Leu in DOT1-like histone H3K79 methyltransferase
25464900 Results provide evidence that transformation driven by MLL fusions as well as the recurrent AML-associated NUP98-NSD1 fusion oncogene is critically dependent on the ability of AF10 to stimulate DOT1L activity.
25417107 Studies identified the evolutionarily conserved Af9 YEATS domain as a novel acetyllysine-binding module and established a direct link between histone acetylation and DOT1L-mediated H3K79 methylation in transcription control.
25005768 DOT1L rs12982744 G to C change and variant C genotype may contribute to knee OA risk in a Chinese Han population.
24916648 A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for myocardial infarction in Japanese
24858818 inhibition of DOT1L, in combination with DNA damaging chemotherapy, represents a promising approach to improving outcomes for MLL-rearranged leukemia.
24854991 Establishing the precise function of DOT1L in normal adult hematopoiesis and understanding its mode of action will aid in our understanding of the use of DOT1L as a therapeutic target in MLL-rearranged leukemia.
24816405 DOT1L Regulates IL-22 Dependent Colon Cancer Stemness via H3K79 Methylation
24486544 PITX2 forms complex with histone H3 lysine 4 (H3K4) methyltransferase. PITX2 complex methylates H3K4.
23996074 Functional studies show that the mapped AF9/ENL interacting site is essential for immortalization by MLL-AF9, indicating that DOT1L interaction with MLL-AF9 and its recruitment are required for transformation by MLL-AF9.
23891621 Interaction with CBX8 precludes AF9-DOT1L binding.
23505243 In male subjects, the rs12982744 polymorphism in DOT1L is associated with hip osteoarthritis.
23012353 a functional interaction between hDOT1L and RNAPII targets hDOT1L and subsequent H3K79 methylations to actively transcribed genes.
22619169 Data show that histone monoubiquitylation H2Aub did not influence histone methyltransferase Dot1L activity.
22566624 These data are a further step to better understand the role of Wnt-signaling during chondrogenesis and cartilage homeostasis. DOT1L may represent a therapeutic target for osteoarthritis.
22373577 These findings identify a novel role for Bat3 in regulating DOT1L function, which plays a critical role in DNA damage response.
22190683 down-regulation of DOT1L-mediated H3K79 methylation disturbs proliferation of human cells
22002246 a novel STAT1-DOT1L interaction that is required for the regulation JAK-STAT-inducible gene expression
21873227 Dot1L inhibits HIV-1 LTR-driven reporter gene expression in the presence of HIV-1 Tat
21741597 These data point to DOT1L as a potential therapeutic target in MLL-rearranged leukemia.
20734064 Observational study of gene-disease association. (HuGE Navigator)
20546612 Observational study of gene-disease association. (HuGE Navigator)
20208522 This permitted structure-activity studies of ubiquitylated mononucleosomes that revealed plasticity in the mechanism of hDot1L stimulation and identified surfaces of ubiquitin important for activation.
20203130 study describes for the first time the components of DotCom and links the specific regulation of H3K79 trimethylation by Dot1 and its associated factors to the Wnt/Wingless signaling pathway
19864429 AF17 competes with AF9 to bind Dot1a, decreases Dot1a nuclear expression by possibly facilitating its nuclear export, and relieves Dot1a.AF9-mediated repression of alpha-ENaC and other target genes.
19799466 titration of the level of ubiquitylated histone H2B within the nucleosome revealed a 1:1 stoichiometry of Dot1L activation.
19734945 Impaired recruitment of the histone methyltransferase DOT1L contributes to the incomplete reactivation of tumor suppressor genes upon DNA demethylation.
19443658 the CALM-AF10 fusion protein can also greatly reduce global H3K79 methylation in both human and murine leukemic cells by disrupting the AF10-mediated association of hDOT1L with chromatin
19266077 Observational study of gene-disease association. (HuGE Navigator)
18449190 demonstration, using chemically ubiquitylated H2B, of a direct stimulation of hDot1L-mediated intranucleosomal methylation of H3 K79
18285465 suggesting a widespread mechanism for parallel or sequential recruitment of DOT1L and MLL to genes in their normal "on" state
17855633 Identification of ENL-associated proteins by mass spectrometry revealed enzymes with a known role in transcriptional elongation: pTEFb and DOT1L.
17094487 Altered phosphorylation of histone-H3 is associated with hepatocarcinogenesis
15851025 mistargeting of hDOT1L to Hoxa9 plays an important role in MLL-AF10-mediated leukemogenesis

AA Sequence


Text Mined References (64)

PMID Year Title
27002147 2016 Up-regulation of Histone Methyltransferase, DOT1L, by Matrix Hyaluronan Promotes MicroRNA-10 Expression Leading to Tumor Cell Invasion and Chemoresistance in Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma.
26927674 2016 MLL1 and DOT1L cooperate with meningioma-1 to induce acute myeloid leukemia.
26830124 2016 Evidence that ubiquitylated H2B corrals hDot1L on the nucleosomal surface to induce H3K79 methylation.
26496610 2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
26439302 2015 The PZP Domain of AF10 Senses Unmodified H3K27 to Regulate DOT1L-Mediated Methylation of H3K79.
26385168 2015 Exploring drug delivery for the DOT1L inhibitor pinometostat (EPZ-5676): Subcutaneous administration as an alternative to continuous IV infusion, in the pursuit of an epigenetic target.
26240340 2015 Identification of a functional hotspot on ubiquitin required for stimulation of methyltransferase activity on chromatin.
26199140 2015 DOT1L cooperates with the c-Myc-p300 complex to epigenetically derepress CDH1 transcription factors in breast cancer progression.
26118503 2015 Targeting DOT1L and HOX gene expression in MLL-rearranged leukemia and beyond.
25921540 2015 Degree of recruitment of DOT1L to MLL-AF9 defines level of H3K79 Di- and tri-methylation on target genes and transformation potential.
25576241 2015 Exome sequencing reveals three novel candidate predisposition genes for diffuse gastric cancer.
25464900 2014 AF10 regulates progressive H3K79 methylation and HOX gene expression in diverse AML subtypes.
25417107 2014 AF9 YEATS domain links histone acetylation to DOT1L-mediated H3K79 methylation.
25005768 2014 Association between single nucleotide polymorphisms of DOT1L gene and risk of knee osteoarthritis in a Chinese Han population.
24916648 2015 A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for myocardial infarction in Japanese.
24858818 2014 DOT1L inhibition sensitizes MLL-rearranged AML to chemotherapy.
24854991 2014 The emerging roles of DOT1L in leukemia and normal development.
24816405 2014 IL-22(+)CD4(+) T cells promote colorectal cancer stemness via STAT3 transcription factor activation and induction of the methyltransferase DOT1L.
24486544 2014 PITX2 associates with PTIP-containing histone H3 lysine 4 methyltransferase complex.
23996074 2013 Targeting recruitment of disruptor of telomeric silencing 1-like (DOT1L): characterizing the interactions between DOT1L and mixed lineage leukemia (MLL) fusion proteins.
23891621 2013 CBX8, a component of the Polycomb PRC1 complex, modulates DOT1L-mediated gene expression through AF9/MLLT3.
23563607 2013 Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.
23505243 2013 The DOT1L rs12982744 polymorphism is associated with osteoarthritis of the hip with genome-wide statistical significance in males.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23012353 2012 Human histone H3K79 methyltransferase DOT1L protein [corrected] binds actively transcribing RNA polymerase II to regulate gene expression.
22619169 2012 Histone monoubiquitylation position determines specificity and direction of enzymatic cross-talk with histone methyltransferases Dot1L and PRC2.
22566624 2012 Genome-wide association and functional studies identify the DOT1L gene to be involved in cartilage thickness and hip osteoarthritis.
22373577 2012 Bat3 facilitates H3K79 dimethylation by DOT1L and promotes DNA damage-induced 53BP1 foci at G1/G2 cell-cycle phases.
22190683 2012 Deficiency of H3K79 histone methyltransferase Dot1-like protein (DOT1L) inhibits cell proliferation.
22002246 2011 A novel disrupter of telomere silencing 1-like (DOT1L) interaction is required for signal transducer and activator of transcription 1 (STAT1)-activated gene expression.
21741597 2011 MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by DOT1L.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
20881960 2010 Hundreds of variants clustered in genomic loci and biological pathways affect human height.
20734064 2010 A large-scale candidate gene association study of age at menarche and age at natural menopause.
20546612 2010 The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature.
20208522 2010 Disulfide-directed histone ubiquitylation reveals plasticity in hDot1L activation.
20203130 2010 Linking H3K79 trimethylation to Wnt signaling through a novel Dot1-containing complex (DotCom).
20153263 2010 A higher-order complex containing AF4 and ENL family proteins with P-TEFb facilitates oncogenic and physiologic MLL-dependent transcription.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19864429 2009 AF17 competes with AF9 for binding to Dot1a to up-regulate transcription of epithelial Na+ channel alpha.
19799466 2009 Structure-activity analysis of semisynthetic nucleosomes: mechanistic insights into the stimulation of Dot1L by ubiquitylated histone H2B.
19734945 2009 Impaired recruitment of the histone methyltransferase DOT1L contributes to the incomplete reactivation of tumor suppressor genes upon DNA demethylation.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19443658 2009 Global reduction of the epigenetic H3K79 methylation mark and increased chromosomal instability in CALM-AF10-positive leukemias.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19266077 2009 Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18449190 2008 Chemically ubiquitylated histone H2B stimulates hDot1L-mediated intranucleosomal methylation.
18391950 2008 Identification of ten loci associated with height highlights new biological pathways in human growth.
18285465 2008 DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells.
18220336 2008 Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.
17855633 2007 A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification.
17707234 2007 Modulation of p53 function by SET8-mediated methylation at lysine 382.
17675446 2007 A charge-based interaction between histone H4 and Dot1 is required for H3K79 methylation and telomere silencing: identification of a new trans-histone pathway.
17094487 Expression of Aurora-B kinase and phosphorylated histone H3 in hepatocellular carcinoma.
16751776 2006 A germline-specific class of small RNAs binds mammalian Piwi proteins.
15851025 2005 hDOT1L links histone methylation to leukemogenesis.
15057824 2004 The DNA sequence and biology of human chromosome 19.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12693554 2003 Characterization of long cDNA clones from human adult spleen. II. The complete sequences of 81 cDNA clones.
12628190 2003 Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12123582 2002 Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain.
11347906 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.