Affinage

DOT1L

Histone-lysine N-methyltransferase, H3 lysine-79 specific · UniProt Q8TEK3

Length
1537 aa
Mass
164.9 kDa
Annotated
2026-06-09
100 papers in source corpus 46 papers cited in narrative 46 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DOT1L (KMT4) is the sole histone H3 lysine 79 (H3K79) methyltransferase in eukaryotes, acting within the nucleosome core rather than on a histone tail and depositing the H3K79 methylation mark that broadly tracks with transcriptionally active chromatin (PMID:12080090, PMID:18285465). Catalysis requires productive engagement of the nucleosome acidic patch and is regulated by combinatorial cross-talk: H2B monoubiquitination (at K123/K120) is required for H3K79 trimethylation (PMID:19667127), cryo-EM showing this proceeds through direct ubiquitin–DOT1L hydrophobic contacts for H2BK120ub but through nucleosome distortion for H2BK34ub (PMID:30759380, PMID:35739357), while H4K16 acetylation allosterically stimulates the enzyme and the H4 tail basic patch is needed in trans (PMID:17675446, PMID:33479126); abolishing ubiquitin or acidic-patch binding impairs leukemic cell proliferation (PMID:35172132). Through H3K79 methylation DOT1L mediates DNA damage checkpoint signaling by recruiting the Rad9/53BP1 Tudor-domain readers to breaks (PMID:16166626, PMID:18418382), global genomic nucleotide excision repair via XPC recruitment (PMID:29343685), telomeric silencing through exclusion of Sir proteins (PMID:12080090), and transcription initiation by stabilizing TBP/TFIID occupancy (PMID:34187895). DOT1L also possesses catalytic-independent functions in transcription elongation, cell-fate determination, and histone chaperoning/nucleosome dynamics (PMID:29339748, PMID:33077595). As a transcriptional coactivator it is recruited by sequence-specific and signaling factors—ERα, Zc3h10, AR, and Wnt/β-catenin components—to methylate H3K79 at target loci controlling estrogen response, thermogenesis, MYC expression, and developmental programs (PMID:20203130, PMID:30775443, PMID:33107819, PMID:32814769). In MLL-rearranged leukemia, DOT1L is aberrantly recruited to HOX loci by MLL fusion partners through a defined 10-residue surface binding AF9/ENL (PMID:23996074) and through a zinc-stabilized coiled-coil interface with AF10, both interactions being required for transformation (PMID:29563185, PMID:21398221). DOT1L abundance is further controlled post-translationally by OGT-mediated O-GlcNAcylation at S1511 opposing UBE3C-driven degradation (PMID:34551297) and by CBP-mediated K358 acetylation opposing RNF8-driven degradation (PMID:32042335). Tissue-specific loss reveals essential physiological roles, including a requirement in cardiomyocytes where DOT1L sustains Dystrophin expression and its loss causes dilated cardiomyopathy (PMID:21289070).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2000 High

    Established the first phenotypic role of Dot1, showing it is required for meiotic pachytene checkpoint integrity before its biochemical activity was known.

    Evidence Genetic deletion of DOT1 with meiotic progression assays and Pch2/Sir2 localization microscopy in yeast

    PMID:11029058

    Open questions at the time
    • Did not identify the molecular activity underlying the phenotype
    • Connection to histone methylation not yet known
  2. 2002 High

    Defined the enzyme's substrate—answering what Dot1 does biochemically—by showing it methylates H3K79 in the nucleosome core and that this mark mediates telomeric silencing by controlling Sir protein binding.

    Evidence Active-site and H3-K79 mutagenesis with Sir protein ChIP and silencing reporters in yeast

    PMID:12080090

    Open questions at the time
    • Mechanism of Sir exclusion by methylation not structurally defined
    • Mammalian enzyme not yet characterized
  3. 2005 High

    Linked H3K79 methylation to the DNA damage response, showing it is required for checkpoint adaptor Rad9 phosphorylation and downstream Rad53 activation, and that Rad9/53BP1 reads the mark via its Tudor domain.

    Evidence Genetic deletion/mutation of DOT1, H3-K79, H2B-K123 with Rad53 kinase assays and Rad9 Tudor-domain mutagenesis/ChIP in yeast and human cells

    PMID:15632126 PMID:16166626

    Open questions at the time
    • Did not resolve how methylated K79 is exposed at breaks
    • Structural basis of Tudor–H3K79me recognition not defined here
  4. 2007 High

    Uncovered trans-histone regulation, showing the H4 basic patch and Dot1's own acidic patch are required for H3K79 methylation, defining cross-tail communication in the nucleosome.

    Evidence In vitro methyltransferase and binding assays with histone mutants plus in vivo H4 basic-patch mutagenesis in yeast

    PMID:17675446

    Open questions at the time
    • Atomic basis of the H4-tail requirement awaited later structures
    • Did not address ubiquitin dependence
  5. 2008 High

    Confirmed DOT1L as the sole mammalian H3K79 di/trimethyltransferase and connected its occupancy genome-wide to active transcription.

    Evidence ChIP-chip and ChIP in Dot1l-null fibroblasts with western blots for methylation states

    PMID:18285465

    Open questions at the time
    • Causal direction between methylation and transcription not resolved
    • No mechanism for transcription coupling provided
  6. 2009 High

    Resolved the H2B ubiquitination requirement, showing H2BK123ub is intrinsically required for H3K79 trimethylation independent of confounding histone alterations.

    Evidence Systematic alanine-scanning mutagenesis of H2A/H2B with in vivo methylation assays in yeast

    PMID:19667127

    Open questions at the time
    • Did not define the physical ubiquitin–enzyme contact
    • Did not explain mono- vs trimethylation control
  7. 2010 High

    Defined DOT1L's complex membership (DotCom) including MLL fusion partners and Wnt components, framing both its leukemia relevance and a developmental coactivator role.

    Evidence Mass spectrometry of purified complex with in vitro methylation and Drosophila RNAi gene-expression assays; complementary TAP-MS in mammalian cells identifying AF9/ENL/NPM1

    PMID:20203130 PMID:20431927

    Open questions at the time
    • Functional contribution of individual subunits not dissected
    • NPM1 chaperoning role inferred but not tested
  8. 2011 High

    Demonstrated tissue-specific physiological requirements—hematopoietic homeostasis, MLL-AF9 leukemia dependence, and cardiac function via Dmd—establishing DOT1L as a context-dependent essential regulator.

    Evidence Conditional Dot1l knockout mice, bone-marrow transplantation, oncogene transformation comparisons, and mini-Dmd rescue with locus ChIP

    PMID:21289070 PMID:21398221

    Open questions at the time
    • Did not separate catalytic from scaffolding contributions in each tissue
    • Target gene selectivity mechanism unresolved
  9. 2011 Medium

    Revealed catalytic-dependent mitotic and genome-stability functions, with catalytic-mutant rescue showing H3K79 methyltransferase activity is required for proper spindle/centrosome function, and a separate methylation-independent histone chaperone activity.

    Evidence siRNA with catalytic active/inactive re-expression and mitotic phenotyping in lung cancer cells; in vitro nucleosome assembly/remodeling and histone exchange analysis

    PMID:22190683 PMID:29339748

    Open questions at the time
    • Chaperone mechanism only partially characterized in vitro
    • Link between mitotic defects and specific target genes unclear
  10. 2013 High

    Mapped the AF9/ENL binding determinant to DOT1L residues 865–874, showing this interaction is required for MLL-AF9 immortalization—defining a druggable protein–protein interface in leukemia.

    Evidence Alanine-scanning mutagenesis, biophysical binding studies, and immortalization assays

    PMID:23996074

    Open questions at the time
    • Did not define the AF10 interface
    • Structure of the bound complex not resolved here
  11. 2018 High

    Provided atomic mechanism, showing DOT1L engages the nucleosome acidic patch via a variant arginine anchor and contacts H2BK120-ubiquitin directly through complementary hydrophobic surfaces.

    Evidence Cryo-EM of DOT1L bound to site-specifically ubiquitylated H2BK120 nucleosomes

    PMID:30759380

    Open questions at the time
    • Did not address other ubiquitin sites
    • Allosteric coupling to catalysis only partially visualized
  12. 2018 High

    Crystallized the DOT1L–AF10 coiled-coil interface, showing zinc stabilizes it and its disruption blocks MLL-AF10 transformation, completing the structural picture of leukemic recruitment.

    Evidence X-ray crystallography with structure-guided mutagenesis and transformation assays

    PMID:29563185

    Open questions at the time
    • Did not address how recruitment alters H3K79me genome-wide
    • AF10's higher-order methylation role addressed separately
  13. 2020 High

    Separated catalytic from non-catalytic roles in development, showing DOT1L loss but not catalytic inactivation disrupts neural/glial differentiation and exacerbates elongation defects—revealing a scaffolding function in elongation and cell fate.

    Evidence DOT1L knockout vs catalytic-dead knock-in ESCs with neural differentiation, transcriptomics, and SEC inhibitor epistasis

    PMID:33077595

    Open questions at the time
    • Molecular partners of the scaffolding function not fully defined
    • How the non-catalytic role intersects elongation machinery unresolved
  14. 2020 High

    Defined post-translational control of DOT1L abundance through two opposing modification–degradation axes—O-GlcNAcylation at S1511 blocking UBE3C and CBP acetylation at K358 blocking RNF8—linking metabolic and signaling state to H3K79 methylation output.

    Evidence AP-MS site mapping, mutagenesis, UBE3C/RNF8 co-IP, and functional ChIP at target loci

    PMID:32042335 PMID:34551297

    Open questions at the time
    • Crosstalk between the two modification axes untested
    • Upstream signals regulating these modifications in vivo unclear
  15. 2021 High

    Reframed DOT1L's transcriptional role toward initiation, showing depletion reduces TBP and Pol II occupancy without affecting elongation rate, and that H4K16ac allosterically stimulates the enzyme distinctly from ubiquitin.

    Evidence 4sUDRB-seq, TBP/Pol II ChIP, and proteomics in erythroleukemic cells; in vitro methyltransferase assays with H4K16ac nucleosomes

    PMID:33479126 PMID:34187895

    Open questions at the time
    • How DOT1L stabilizes TFIID mechanistically not resolved
    • Coordination of H4K16ac and ubiquitin allostery only partially defined
  16. 2022 High

    Established a second mode of ubiquitin stimulation, showing H2BK34ub acts through DNA/histone distortion rather than direct contact, and confirmed acidic-patch and ubiquitin binding are required for leukemic proliferation.

    Evidence Cryo-EM of Dot1L-H2BK34ub nucleosomes and single-molecule biophysics with structure-guided mutagenesis in MLL-rearranged cells

    PMID:35172132 PMID:35739357

    Open questions at the time
    • Relative contribution of each ubiquitin mode in vivo unclear
    • Distortion mechanism for other modifications untested
  17. 2022 High

    Expanded DOT1L's physiological reach as a factor-recruited coactivator across cardiogenesis, brown-fat thermogenesis, atherosclerosis, and germline/stem-cell programs, in some cases also silencing genes.

    Evidence Tissue-specific conditional Dot1l knockouts with H3K79me2 ChIP-seq and transcriptomics across heart, brown adipose (Zc3h10), VSMC/macrophage, and spermatogonial models

    PMID:33107819 PMID:35292818 PMID:35738678 PMID:36417856 PMID:36460641

    Open questions at the time
    • Mechanism of locus-specific silencing by an activating mark unresolved
    • Determinants of tissue-specific target selection unclear
  18. 2024 Medium

    Positioned DOT1L within transcriptional regulatory loops with c-Myc/MYC and a PARP1-driven resistance axis, showing it both activates oncogenic targets and is itself transcriptionally controlled.

    Evidence ChIP/CUT&Tag for H3K79me2 at MYC and PLCG2/ABCB1 loci, PARP1 promoter ChIP, and rescue experiments in colorectal, prostate, and PARPi-resistance models

    PMID:31888761 PMID:32814769 PMID:38778348

    Open questions at the time
    • Single-lab findings without reciprocal validation across models
    • Generality of the PARP1-DOT1L axis across tumor types untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DOT1L achieves locus-specific target selection—and how its single H3K79 mark can both activate and silence distinct genes within the same cell—remains unresolved.
  • No unifying model linking recruitment factors to context-dependent activation vs silencing
  • Mechanistic basis of the catalytic-independent scaffolding function incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0140110 transcription regulator activity 4 GO:0042393 histone binding 2 GO:0044183 protein folding chaperone 1
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-73894 DNA Repair 4 R-HSA-1266738 Developmental Biology 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
AF10AF9ENLNPM1OGTRNF8UBE3CZC3H10
Complex memberships
DotCom

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Dot1 (yeast ortholog of DOT1L) methylates lysine 79 of histone H3 within the globular domain of the nucleosome, not the tail. Mutations abolishing Dot1 catalytic activity impair telomeric silencing, and this correlates with weakened interaction of Sir2 and Sir3 with telomeric regions in vivo, establishing H3K79 methylation as the mechanism by which Dot1 mediates telomeric silencing. In vivo mutagenesis of H3-K79 and Dot1 catalytic residues; Sir protein ChIP; telomeric silencing reporter assays Genes & development High 12080090
2000 Yeast Dot1 is required for meiotic pachytene checkpoint function: in dot1 mutants, synapsis-defective (zip1, dmc1) cells bypass the checkpoint and produce inviable meiotic products. Dot1 is also required for proper nucleolar concentration of checkpoint proteins Pch2 and Sir2, and for preventing sister-chromatid repair by the Rad54 pathway during meiosis. Genetic deletion of DOT1; meiotic progression assays; fluorescence microscopy of Pch2/Sir2 localization Molecular biology of the cell High 11029058
2005 Dot1-dependent H3K79 methylation is required for DNA damage checkpoint activation in S. cerevisiae: loss of H3K79 methylation does not affect Mec1 activation but prevents phosphorylation of the checkpoint adaptor Rad9, thereby blocking Rad53 kinase activation and causing checkpoint deficiency. Genetic deletion/mutation of DOT1, H3-K79, H2B-K123; Rad53 kinase phosphorylation assays; cell cycle arrest assays after genotoxic stress The Journal of biological chemistry High 15632126 16166626
2005 Dot1/H3K79 methylation mediates G1 and intra-S phase checkpoint activation after ionizing radiation by enabling Rad9 (yeast 53BP1 ortholog) binding to double-strand break sites via its Tudor domain; Tudor domain mutations in Rad9 that abrogate methylated K79 binding phenocopy dot1 deletion and block Rad53 phosphorylation. In human cells, DOT1L-mediated H3K79 methylation similarly mediates 53BP1 recruitment to DSBs via its paired Tudor domains. Genetic screen; Rad9 Tudor domain mutagenesis; Rad53 phosphorylation assays; ChIP for Rad9 at DSBs Molecular and cellular biology High 16166626
2007 Dot1 requires the basic patch residues R17-H18-R19 of the histone H4 N-terminal tail for H3K79 methyltransferase activity in vitro and in vivo. Dot1 physically interacts with the H4 tail via its own C-terminal acidic patch. This defines a novel trans-histone pathway whereby H4 tail charge is required for modification of H3K79. In vitro methyltransferase assay with histone mutants; in vitro binding assay (H4 tail pulldown); in vivo mutagenesis of H4 basic patch and Dot1 acidic patch; telomere silencing assays Genes & development High 17675446
2008 Dot1-dependent H3K79 methylation promotes Rad9 binding to chromatin at DSBs and uncapped telomeres, and Rad9/H3K79me together inhibit resection of DSBs by a Rad50-dependent nuclease, controlling ssDNA accumulation and thereby modulating Mec1 checkpoint kinase activation. Genetic deletion (dot1Δ, rad9Δ); ssDNA accumulation assays at DSBs and uncapped telomeres; Mec1 activation assays The EMBO journal High 18418382
2008 DOT1L is the sole H3K79 di- and trimethyltransferase in mammalian cells; Dot1l mutant fibroblasts lack H3K79 di- and trimethylation at all loci. DOT1L occupancy is ubiquitously coupled with active transcription, preferentially at the proximal transcribed region of active genes, and H3K79 methylation levels dynamically respond to changes in gene activity. ChIP-chip tiling arrays; ChIP in Dot1l mutant fibroblasts; western blot for H3K79 methylation states Molecular and cellular biology High 18285465
2009 H2B monoubiquitination at K123 is required for both H3K4 trimethylation by COMPASS and H3K79 trimethylation by Dot1; this dependency is intrinsic to H2BK123 monoubiquitination regardless of additional H2B sequence alterations or epitope tags. Systematic alanine-scanning mutagenesis of histone H2A/H2B; in vivo methylation assays The Journal of cell biology High 19667127
2009 Dot1 and its H3K79 methylation promote sister chromatid recombination (SCR) repair of replication-dependent DSBs in yeast; Dot1 and Rad9 promote DSB-induced loading of cohesin onto chromatin, suggesting that Rad9 recruitment via gammaH2A and H3K79me at DSBs contributes to SCR by regulating cohesin binding. Genetic epistasis; SCR assays; cohesin ChIP at DSBs Genetics Medium 19332880
2010 DOT1L forms a multisubunit complex (DotCom) with MLL fusion partners ENL, AF9/MLLT3, AF17/MLLT6, and AF10/MLLT10, as well as Wnt pathway components TRRAP, Skp1, and beta-catenin. DotCom trimethylates H3K79 and is required for Wnt/Wingless target gene expression in Drosophila; depletion of Bre1 (H2B ubiquitin E3 ligase) specifically reduces H3K79 trimethylation and Wingless target gene expression. Mass spectrometry of purified complex; H3K79 trimethylation in vitro assay; Drosophila RNAi knockdown; gene expression assays Genes & development High 20203130
2011 Cardiac-specific knockout of Dot1L in mice results in dilated cardiomyopathy. Mechanistically, DOT1L regulates transcription of the Dystrophin (Dmd) gene; loss of DOT1L reduces H3K79 methylation at the Dmd locus, decreasing Dystrophin expression and destabilizing the Dystrophin-glycoprotein complex. Re-expression of miniDmd rescues the DCM phenotype, establishing Dmd as a primary downstream target. Conditional cardiac-specific Dot1L knockout mice; ChIP for H3K79me at Dmd locus; mini-Dmd rescue experiment; protein complex analysis Genes & development High 21289070
2011 Conditional deletion of Dot1l in postnatal mouse hematopoiesis causes pancytopenia and failure of hematopoietic homeostasis; Dot1l-deficient cells fail to reconstitute recipient bone marrow. MLL-AF9 leukemic cells specifically require Dot1l for oncogenic transformation, whereas cells driven by Hoxa9/Meis1 or E2A-HLF do not. Conditional Dot1l knockout mouse model; competitive bone marrow transplantation; MLL-AF9, Hoxa9/Meis1, and E2A-HLF transformation assays Blood High 21398221
2011 DOT1L deficiency in lung cancer cells causes multinucleated phenotype, abnormal mitotic spindle formation, and centrosome number abnormalities leading to chromosomal missegregation, G1 arrest, and senescence. Re-expression of catalytically active but not inactive DOT1L rescues these phenotypes, establishing the requirement for H3K79 methyltransferase activity. siRNA knockdown of DOT1L; catalytically active vs. inactive DOT1L re-expression; cell cycle analysis; mitotic spindle immunofluorescence; senescence-associated β-galactosidase assay The Journal of biological chemistry High 22190683
2011 Dot1 displays histone chaperone activity independent of its methyltransferase activity: Dot1 can assemble core histones into nucleosomes and facilitate ATP-dependent chromatin-remodeling activity via its nucleosome-binding domain in vitro; this chaperone function regulates histone exchange and nucleosome dynamics at transcribed regions of long genes in vivo. In vitro nucleosome assembly assay; in vitro chromatin remodeling assay; global histone exchange analysis; genetic analysis of cryptic transcription Nature communications Medium 29339748
2013 DOT1L interacts with MLL fusion partners AF9 and ENL through a specific 10-amino acid region (DOT1L865-874) containing four conserved hydrophobic residues; the entire intact C-terminal domain of AF9/ENL is required for optimal interaction. This interaction is essential for immortalization by MLL-AF9, as alanine mutations at the binding site abrogate transformation. Alanine scanning mutagenesis; biochemical/biophysical binding studies; functional immortalization assays The Journal of biological chemistry High 23996074
2013 Dot1-dependent H3K79 methylation is required for Mek1 meiotic checkpoint kinase autophosphorylation (but not Mec1/Tel1-dependent phosphorylation) during meiosis; H3K79me promotes Hop1 activation and proper distribution along meiotic chromosomes at least partly by regulating Pch2 localization. HOP1 overexpression bypasses the Dot1 requirement for checkpoint activation. Genetic manipulation of Dot1 catalytic activity; H3-K79 mutagenesis; Mek1 kinase activity assays; meiotic chromosome spreads; HOP1 overexpression epistasis PLoS genetics High 23382701
2018 Structural analysis by cryo-EM of DOT1L bound to a nucleosome containing site-specifically ubiquitylated H2BK120 reveals that DOT1L engages the nucleosome acidic patch using a variant arginine anchor and adopts a conformation poised for methylation; DOT1L and ubiquitin interact directly through complementary hydrophobic surfaces, explaining how H2BK120ub stimulates DOT1L activity. Cryo-EM structure determination; site-specific ubiquitylation of H2BK120 in reconstituted nucleosomes Cell reports High 30759380
2018 Crystal structure of apo AF10OM-LZ and its complex with the coiled-coil domain of DOT1L reveals the molecular basis for DOT1L-AF10 interaction; zinc stabilizes the complex. Disruption of the DOT1L-AF10 interface abrogates MLL-AF10-associated leukemic transformation. X-ray crystallography; structure-guided mutagenesis; leukemic transformation assay Genes & development High 29563185
2019 DOT1L functions as a cofactor of ERα in breast cancer cell chromatin, where the two proteins co-localize to regulate estrogen target gene transcription. DOT1L blockade reduces H3K79 methylation and ERα/FOXA1 gene expression, blocking proliferation of hormone-responsive and antiestrogen-resistant breast cancer cells. ChIP-seq co-localization; siRNA knockdown and pharmacological inhibition; gene expression analysis; in vivo xenograft Science advances Medium 30775443
2020 DOT1L loss (KO), but not catalytic inactivation, causes defects in neural progenitor cell gene expression signature and glial cell specification in ESC differentiation, and exacerbates transcription elongation defects induced by a super elongation complex inhibitor; revealing a catalytic-independent role of DOT1L in transcription elongation and cell-fate determination. DOT1L knockout vs. catalytic-dead knock-in ESCs; neural differentiation assays; transcriptome analysis; super elongation complex inhibitor (KL-2) epistasis Proceedings of the National Academy of Sciences of the United States of America High 33077595
2020 DOT1L protein stability is regulated by O-GlcNAcylation at evolutionarily conserved S1511, mediated by OGT. O-GlcNAcylation at S1511 prevents binding of the E3 ubiquitin ligase UBE3C, which otherwise promotes DOT1L proteasomal degradation. HBP-enhanced O-GlcNAcylation increases H3K79 methylation and expression of HOXA9/MEIS1 target genes. Affinity purification-mass spectrometry; site-directed mutagenesis of S1511; co-immunoprecipitation of UBE3C-DOT1L; OGT inhibition/HBP pathway manipulation; ChIP for H3K79me Cell reports High 34551297
2020 CBP mediates DOT1L acetylation at K358, stabilizing DOT1L by preventing RNF8 E3 ubiquitin ligase binding and subsequent proteasomal degradation without affecting enzymatic activity. Stabilized DOT1L then catalyzes H3K79 methylation at promoters of SNAIL and ZEB1, promoting EMT and cancer metastasis. Affinity purification-mass spectrometry; co-IP of RNF8-DOT1L; DOT1L K358 acetylation-mimic mutant; ChIP for H3K79me at EMT gene promoters; in vivo metastasis assay Theranostics High 32042335
2020 Dot1L interacts directly with the transcription factor Zc3h10 and is recruited to promoters of thermogenic genes including Ucp1 in brown adipose tissue; Dot1L methylates H3K79 at these promoters to coactivate gene expression. Dot1L ablation in brown adipocytes (Ucp1-Cre) prevents Ucp1 and other thermogenic gene activation, reduces thermogenic capacity, and promotes adiposity. Co-immunoprecipitation; ChIP; conditional Dot1L KO (Ucp1-Cre); thermogenic gene expression; metabolic phenotyping eLife High 33107819
2021 DOT1L depletion in erythroleukemic cells reduces TBP occupancy on thousands of genes and reduces Pol II occupancy at a significant fraction of direct DOT1L-bound target genes, indicating a role in transcription initiation rather than elongation (no effect on Pol II traveling ratio or elongation rate). Mechanistically, the DOT1L complex may regulate initiation by facilitating TFIID recruitment/stabilization; DOT1L also limits SAGA deubiquitinase recruitment to maintain H2Bub1 levels. DOT1L depletion; 4sUDRB-seq (elongation rate); TBP/Pol II ChIP; proteomic and biochemical studies; SAGA complex recruitment assays Proceedings of the National Academy of Sciences of the United States of America High 34187895
2021 H4K16 acetylation allosterically stimulates yeast Dot1 H3K79 methyltransferase activity in a manner distinct from but coordinating with H2B ubiquitination (H2BUb). H4K16ac and H2BUb play crucial roles specifically in H3K79 di- and trimethylation in vitro and in vivo. In vitro methyltransferase assay with H4K16ac-modified nucleosomes; in vivo methylation state analysis; mechanistic structural/biochemical analysis Science (New York, N.Y.) High 33479126
2021 AF10 (MLLT10) interacts with DOT1L and is required for higher-order H3K79 methylation in somatic cells; AF10-DOT1L interaction (but not a DOT1L-binding-impaired AF10 mutant) maintains H3K79 methylation and acts as a barrier to somatic cell reprogramming by sustaining fibroblast-specific gene programs. Proximity-based labeling proteomics; AF10 KO and re-expression; DOT1L-binding-impaired AF10 mutant rescue; H3K79 methylation western blot; transcriptomic analysis during reprogramming Epigenetics & chromatin High 34215314
2021 Dot1 promotes H2B monoubiquitination through its N-terminus in a methyltransferase-independent manner; increased Dot1 dosage elevates H2Bub1 levels and this is exacerbated by loss of SAGA-DUB deubiquitinase activity, establishing bidirectional crosstalk between Dot1 and H2Bub1. Genetic interaction mapping with increased-dosage DOT1 alleles; H2Bub1 western blot; N-terminal deletion mutants of Dot1 Nucleic acids research Medium 30203048
2022 Cryo-EM structures of Dot1L bound to H2BK34ub nucleosomes reveal that H2BK34-anchored ubiquitin does not directly contact Dot1L (unlike H2BK120ub), but instead induces DNA and histone distortion around the modified site to position Dot1L in a productive conformation, establishing nucleosome distortion as a distinct mechanism by which ubiquitination stimulates Dot1L. Cryo-EM structure determination of Dot1L-H2BK34ub nucleosome complex and H2BK34ub nucleosome alone; site-specific ubiquitylation Nature chemical biology High 35739357
2022 DOT1L activity requires ubiquitin and nucleosome acidic patch binding for productive nucleosome engagement; these interactions drive conformational changes that stimulate DOT1L activity. Structure-guided mutations abolishing either ubiquitin or acidic patch binding impair cell proliferation in MV4;11 MLL-rearranged leukemia cells. Bulk and single-molecule biophysical measurements; structure-guided mutagenesis; cancer cell proliferation assays Cell reports High 35172132
2022 H3K79me2 in DOT1L-regulated gene bodies and regulatory elements synergizes to promote expression of chamber-specific genes during cardiogenesis (particularly left ventricle-specific genes); H3K79me2 at specific regulatory elements also contributes to silencing of genes normally not expressed in cardiomyocytes. Embryonic cardiomyocyte-specific Dot1l ablation impairs postnatal cardiomyocyte cell cycle withdrawal. Embryonic cardiomyocyte-specific Dot1l conditional KO; H3K79me2 ChIP-seq; transcriptome analysis; cardiomyocyte cell cycle analysis Nature communications High 36460641
2022 DOT1L directly regulates the transcription of NF-κB1 and NF-κB2 in vascular smooth muscle cells via H3K79me2 enrichment at their loci, which in turn induces expression of CCL5 and CXCL10, promoting atherosclerosis. VSMC-specific Dot1l KO in ApoE-/- mice significantly reduces atherosclerosis progression. VSMC-specific inducible KO mouse crossed with ApoE-/- model; RNA-seq; H3K79me2 ChIP-seq; VSMC phenotyping European heart journal High 35292818
2018 Dot1 binding to chromatin can deregulate heterochromatin-mediated silencing by both H3K79 methylation-dependent and methylation-independent mechanisms; the methylation-independent mechanism requires histone acetyltransferase Gcn5 and can relocalize telomeres away from the nuclear periphery. Targeted Dot1 tethering; H3K79 methylation-dead Dot1 mutant; live-cell telomere imaging; genetic epistasis with Gcn5 Epigenetics & chromatin Medium 21291527
2011 H3K79 methylation by Dot1 is required for global genomic repair (GGR) but not transcription-coupled repair (TCR) of UV damage in yeast; both mono/di/trimethylation states contribute to GGR, and the mechanism is independent of checkpoint activation or Rad16 expression regulation, suggesting methylated H3K79 serves as a docking site for GGR machinery. Dot1 deletion and H3K79 mutation; GGR vs. TCR assays; checkpoint activation analysis; Rad16 expression analysis The Journal of biological chemistry Medium 21460225
2018 DOT1L-methylated H3K79 is involved in binding and recruiting XPC to UV-damage sites for nucleotide excision repair (NER); DOT1L loss impairs NER, leading to accumulation of UV-induced DNA damage and promotion of melanoma development in mice exposed to UV radiation. DOT1L KO mice + UVR; ChIP showing H3K79me at damage sites; XPC recruitment assay; NER efficiency measurement Nature communications Medium 29343685
2017 DOT1L is recruited by the ENL-containing DOT1L complex to maintain transcription of MLL fusion target genes; MLL-ENL and MLL-AF10 constitutively activate transcription by inducing both AEP (AF4-ENL-P-TEFb)-dependent transcriptional activation and DOT1L-dependent transcriptional maintenance, mostly in the absence of PRC1. Genetic and biochemical analysis of complex membership; gene expression analysis; transformation assays with MLL-ENL and MLL-AF10 The Journal of clinical investigation Medium 28394257
2016 DOT1L, via H3K79 dimethylation, facilitates histone H4 acetylation, which in turn regulates BRD4 binding to chromatin; BRD4 and DOT1L exist in separate protein complexes but functionally collaborate, especially at highly transcribed genes near superenhancers in MLL leukemia. Quantitative proteomics; chemoproteomics; biochemical fractionation; genetic disruption and small-molecule inhibition of BRD4 and DOT1L; H4 acetylation ChIP Nature structural & molecular biology High 27294782
2020 DOT1L inhibition in AR-positive prostate cancer cells reduces MYC expression by loss of H3K79 methylation at a distal MYC enhancer bound by AR and DOT1L; reduced MYC upregulates E3 ubiquitin ligases HECTD4 and MYCBP2, which promote AR and MYC proteasomal degradation in a negative feedforward loop. DOT1L knockdown/inhibition in AR+ vs AR- cells; ChIP for H3K79me at MYC enhancer; MYC expression; E3 ligase identification; AR/MYC protein stability assays Nature communications High 32814769
2022 SESAME complex-catalyzed H3T11 phosphorylation directly reduces Dot1 binding to chromatin and inhibits Dot1-catalyzed H3K79 trimethylation, thereby repressing autophagy gene transcription; the Reb1 telomere-associated factor recruits SESAME to telomeres to phosphorylate H3T11, preventing invasion of H3K79me3 into heterochromatin to maintain telomere silencing. Chromatin binding assays; H3K79me3 in vitro/in vivo methylation assays; autophagy gene expression assays; ChIP; Reb1 tethering at telomeres Nature communications Medium 36473858
2022 H3K79me3 is selectively enriched at pericentromeric repetitive elements relative to H3K79me2 in mouse ESCs; DOT1L loss compromises pericentromeric satellite repeat transcription, destabilizes pericentromeric heterochromatin, and impairs preimplantation viability. This involves possible coordination between DOT1L and the chromatin remodeler SMARCA5. H3K79me2/me3 ChIP-seq; DOT1L KO ESCs and cleavage-stage embryos; satellite repeat transcription assays; heterochromatin marker analysis EMBO reports Medium 37317657
2022 DOT1L directly regulates macrophage lipid biosynthesis gene programs including central regulators SREBP1 and SREBP2; DOT1L inhibition leads to macrophage hyperactivation, and myeloid-specific Dot1l deficiency reduces atherosclerotic plaque stability in vivo. Selective DOT1L inhibitor in mouse and human macrophages; myeloid-specific Dot1l KO mice; RNA-seq; SREBP pathway analysis; atherosclerosis plaque analysis Cell reports Medium 36417856
2021 DOT1L promotes expression of HoxC transcription factors (HoxC9, HoxC10) in spermatogonial stem cells; H3K79me2 accumulates at HoxC9 and HoxC10 loci, and DOT1L is required for spermatogonial stem cell self-renewal and lifelong spermatogenesis. Conditional DOT1L KO in male germline; H3K79me2 ChIP at HoxC9/HoxC10; spermatogonial stem cell transplantation assay; gene expression analysis Genes & development High 35738678
2023 DOT1L inhibition in apical progenitors (neural stem cells) increases neurogenic symmetric consumptive divisions over self-renewing asymmetric divisions, reduces activity of EZH2/PRC2 pathway, and converges on increased expression of asparagine synthetase (ASNS); ASNS overexpression phenocopies DOT1L inhibition, linking DOT1L activity to asparagine metabolism and neural stem cell lineage progression. Lineage tracing combined with single-cell RNA-seq of clonally related cells; DOT1L inhibition; ASNS overexpression; PRC2 pathway analysis EMBO reports Medium 37382163
2021 DOT1L epigenetically promotes c-Myc transcription via H3K79me2 enrichment at the c-Myc promoter region (-682 to +284); H3K79me2 enrichment at this region is reduced after DOT1L knockdown, and c-Myc restoration rescues cell cycle arrest caused by DOT1L silencing in colorectal cancer cells. ChIP for H3K79me2 at c-Myc promoter; DOT1L siRNA knockdown; c-Myc rescue experiments; cell cycle analysis Clinical epigenetics Medium 31888761
2010 Tandem affinity purification of DOT1L-containing complexes revealed that AF9, ENL, and NPM1 are major DOT1L-interacting proteins in mammalian cells; separate purification of AF9-, ENL-, and NPM1-containing complexes by mass spectrometry further defined a DOT1L interaction network suggesting roles in AF9/ENL-mediated transcription, RNA processing, and histone chaperoning via NPM1. Tandem affinity purification; mass spectrometry The protein journal Medium 20431927
2019 DOT1L is required for proper DNA double-strand break response and repair via homologous recombination (HR) in colorectal cancer cells; DOT1L depletion or inhibition impairs γH2AX phosphorylation and HR repair efficiency, and DOT1L inhibition combined with chemotherapy shows additive effects on cell killing. siRNA knockdown and small-molecule inhibitors; γH2AX assay; HR repair assay; drug combination assays Clinical epigenetics Medium 30616689
2024 PARP1 directly binds to the DOT1L gene promoter and promotes DOT1L transcription independently of its enzymatic activity; PARPi-induced PARP1 trapping amplifies this binding, enhancing DOT1L transcription. DOT1L in turn regulates PLCG2 and ABCB1 via H3K79me2, establishing a PARP1-DOT1L-PLCG2/ABCB1 resistance axis. ChIP for PARP1 at DOT1L promoter; RNA sequencing; CUT&Tag for H3K79me2 at PLCG2/ABCB1 loci; PARPi treatment; CDX and PDO models Molecular cancer Medium 38778348

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 The diverse functions of Dot1 and H3K79 methylation. Genes & development 467 21724828
2002 Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association. Genes & development 429 12080090
2008 DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells. Molecular and cellular biology 399 18285465
2010 Linking H3K79 trimethylation to Wnt signaling through a novel Dot1-containing complex (DotCom). Genes & development 260 20203130
2005 The DNA damage checkpoint response requires histone H2B ubiquitination by Rad6-Bre1 and H3 methylation by Dot1. The Journal of biological chemistry 243 15632126
2005 Role of Dot1-dependent histone H3 methylation in G1 and S phase DNA damage checkpoint functions of Rad9. Molecular and cellular biology 241 16166626
2011 Requirement for Dot1l in murine postnatal hematopoiesis and leukemogenesis by MLL translocation. Blood 171 21398221
2018 DOT1L and H3K79 Methylation in Transcription and Genomic Stability. Biomolecules 166 29495487
2008 Histone methyltransferase Dot1 and Rad9 inhibit single-stranded DNA accumulation at DSBs and uncapped telomeres. The EMBO journal 163 18418382
2000 Role for the silencing protein Dot1 in meiotic checkpoint control. Molecular biology of the cell 139 11029058
2010 Histone H3 lysine 79 methyltransferase Dot1 is required for immortalization by MLL oncogenes. Cancer research 138 21159644
2006 Selective di- or trimethylation of histone H3 lysine 76 by two DOT1 homologs is important for cell cycle regulation in Trypanosoma brucei. Molecular cell 122 16916638
2011 DOT1L regulates dystrophin expression and is critical for cardiac function. Genes & development 121 21289070
2017 DOT1L safeguards cartilage homeostasis and protects against osteoarthritis. Nature communications 120 28627522
2011 Deficiency of H3K79 histone methyltransferase Dot1-like protein (DOT1L) inhibits cell proliferation. The Journal of biological chemistry 116 22190683
2019 Structural Basis for Recognition of Ubiquitylated Nucleosome by Dot1L Methyltransferase. Cell reports 111 30759380
2009 Histone H2BK123 monoubiquitination is the critical determinant for H3K4 and H3K79 trimethylation by COMPASS and Dot1. The Journal of cell biology 108 19667127
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. Genes & development 106 17675446
2014 The emerging roles of DOT1L in leukemia and normal development. Leukemia 102 24854991
2016 Complementary activities of DOT1L and Menin inhibitors in MLL-rearranged leukemia. Leukemia 99 27840424
2014 The histone methyltransferase Dot1/DOT1L as a critical regulator of the cell cycle. Cell cycle (Georgetown, Tex.) 97 24526115
2021 Regulation of the Dot1 histone H3K79 methyltransferase by histone H4K16 acetylation. Science (New York, N.Y.) 92 33479126
2016 Functional interdependence of BRD4 and DOT1L in MLL leukemia. Nature structural & molecular biology 92 27294782
2011 Dot1 and histone H3K79 methylation in natural telomeric and HM silencing. Molecular cell 92 21474073
2020 Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer. Nature communications 91 32814769
2016 The upstreams and downstreams of H3K79 methylation by DOT1L. Chromosoma 89 26728620
2019 Inhibition of histone methyltransferase DOT1L silences ERα gene and blocks proliferation of antiestrogen-resistant breast cancer cells. Science advances 82 30775443
2022 H2B Lys34 Ubiquitination Induces Nucleosome Distortion to Stimulate Dot1L Activity. Nature chemical biology 80 35739357
2013 A medicinal chemistry perspective for targeting histone H3 lysine-79 methyltransferase DOT1L. Journal of medicinal chemistry 68 23879463
2009 ES cell cycle progression and differentiation require the action of the histone methyltransferase Dot1L. Stem cells (Dayton, Ohio) 66 19544450
2014 DOT1L inhibition sensitizes MLL-rearranged AML to chemotherapy. PloS one 65 24858818
2017 The Histone Methyltransferase DOT1L Promotes Neuroblastoma by Regulating Gene Transcription. Cancer research 63 28209620
2022 DOT1L Is a Novel Cancer Stem Cell Target for Triple-Negative Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 61 35135840
2020 DOT1L-controlled cell-fate determination and transcription elongation are independent of H3K79 methylation. Proceedings of the National Academy of Sciences of the United States of America 60 33077595
2019 DOT1L: a key target in normal chromatin remodelling and in mixed-lineage leukaemia treatment. Epigenetics 60 31790636
2018 The protective role of DOT1L in UV-induced melanomagenesis. Nature communications 60 29343685
2017 Cooperative gene activation by AF4 and DOT1L drives MLL-rearranged leukemia. The Journal of clinical investigation 59 28394257
2022 The epigenetic enzyme DOT1L orchestrates vascular smooth muscle cell-monocyte crosstalk and protects against atherosclerosis via the NF-κB pathway. European heart journal 58 35292818
2022 Targeting the histone H3 lysine 79 methyltransferase DOT1L in MLL-rearranged leukemias. Journal of hematology & oncology 57 35331314
2019 The histone methyltransferase DOT1L is required for proper DNA damage response, DNA repair, and modulates chemotherapy responsiveness. Clinical epigenetics 56 30616689
2015 Mixed lineage rearranged leukaemia: pathogenesis and targeting DOT1L. Current opinion in hematology 53 25635757
2013 Dot1-dependent histone H3K79 methylation promotes activation of the Mek1 meiotic checkpoint effector kinase by regulating the Hop1 adaptor. PLoS genetics 52 23382701
2018 The histone methyltransferase DOT1L inhibits osteoclastogenesis and protects against osteoporosis. Cell death & disease 51 29348610
2011 Evidence that the histone methyltransferase Dot1 mediates global genomic repair by methylating histone H3 on lysine 79. The Journal of biological chemistry 51 21460225
2010 Characterization of the DOT1L network: implications of diverse roles for DOT1L. The protein journal 49 20431927
2021 DOT1L O-GlcNAcylation promotes its protein stability and MLL-fusion leukemia cell proliferation. Cell reports 48 34551297
2021 DOT1L complex regulates transcriptional initiation in human erythroleukemic cells. Proceedings of the National Academy of Sciences of the United States of America 47 34187895
2019 DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortex. Nucleic acids research 46 30329130
2009 The Dot1 histone methyltransferase and the Rad9 checkpoint adaptor contribute to cohesin-dependent double-strand break repair by sister chromatid recombination in Saccharomyces cerevisiae. Genetics 46 19332880
2020 CBP mediated DOT1L acetylation confers DOT1L stability and promotes cancer metastasis. Theranostics 44 32042335
2019 Silencing or inhibition of H3K79 methyltransferase DOT1L induces cell cycle arrest by epigenetically modulating c-Myc expression in colorectal cancer. Clinical epigenetics 44 31888761
2019 miR-133b suppresses colorectal cancer cell stemness and chemoresistance by targeting methyltransferase DOT1L. Experimental cell research 43 31525340
2008 Role of Dot1 in the response to alkylating DNA damage in Saccharomyces cerevisiae: regulation of DNA damage tolerance by the error-prone polymerases Polzeta/Rev1. Genetics 42 18562671
2015 DOT1L Activity Promotes Proliferation and Protects Cortical Neural Stem Cells from Activation of ATF4-DDIT3-Mediated ER Stress In Vitro. Stem cells (Dayton, Ohio) 40 26299268
2022 Histone Methyltransferase DOT1L as a Promising Epigenetic Target for Treatment of Solid Tumors. Frontiers in genetics 39 35495127
2021 Histone methyltransferase DOT1L controls state-specific identity during B cell differentiation. EMBO reports 38 33410591
2013 Targeting recruitment of disruptor of telomeric silencing 1-like (DOT1L): characterizing the interactions between DOT1L and mixed lineage leukemia (MLL) fusion proteins. The Journal of biological chemistry 38 23996074
2020 The Histone Methyltransferase DOT1L Is Essential for Humoral Immune Responses. Cell reports 37 33326791
2016 MLL1 and DOT1L cooperate with meningioma-1 to induce acute myeloid leukemia. The Journal of clinical investigation 35 26927674
2022 The histone methyltransferase DOT1L is a new epigenetic regulator of pulmonary fibrosis. Cell death & disease 34 35039472
2020 The Methyltransferase DOT1L Controls Activation and Lineage Integrity in CD4+ T Cells during Infection and Inflammation. Cell reports 34 33326781
2018 Dot1 regulates nucleosome dynamics by its inherent histone chaperone activity in yeast. Nature communications 33 29339748
2018 DOT1L inhibition blocks multiple myeloma cell proliferation by suppressing IRF4-MYC signaling. Haematologica 33 30171029
2010 Regulation of tolerance to DNA alkylating damage by Dot1 and Rad53 in Saccharomyces cerevisiae. DNA repair 31 20674515
2022 DOT1L regulates lipid biosynthesis and inflammatory responses in macrophages and promotes atherosclerotic plaque stability. Cell reports 30 36417856
2010 Targeting DOT1L action and interactions in leukemia: the role of DOT1L in transformation and development. Expert opinion on therapeutic targets 30 20230194
2022 Histone methyltransferase DOT1L is essential for self-renewal of germline stem cells. Genes & development 29 35738678
2018 Dot1 promotes H2B ubiquitination by a methyltransferase-independent mechanism. Nucleic acids research 29 30203048
2021 Hypoxia induces DOT1L in articular cartilage to protect against osteoarthritis. JCI insight 28 34727094
2011 Dot1 binding induces chromatin rearrangements by histone methylation-dependent and -independent mechanisms. Epigenetics & chromatin 28 21291527
2018 Peptidomimetics for Targeting Protein-Protein Interactions between DOT1L and MLL Oncofusion Proteins AF9 and ENL. ACS medicinal chemistry letters 26 30258537
2022 DOT1L regulates chamber-specific transcriptional networks during cardiogenesis and mediates postnatal cell cycle withdrawal. Nature communications 23 36460641
2017 The Putative Histone Methyltransferase DOT1 Regulates Aflatoxin and Pathogenicity Attributes in Aspergillus flavus. Toxins 23 28737735
2018 Structural and functional analysis of the DOT1L-AF10 complex reveals mechanistic insights into MLL-AF10-associated leukemogenesis. Genes & development 21 29563185
2014 Dot1-dependent histone H3K79 methylation promotes the formation of meiotic double-strand breaks in the absence of histone H3K4 methylation in budding yeast. PloS one 21 24797370
2024 Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic and Myeloid Leukemia. International journal of molecular sciences 20 38892207
2020 Intracellular Delivery of DNA and Protein by a Novel Cell-Permeable Peptide Derived from DOT1L. Biomolecules 20 32024261
2018 Transcriptional activator DOT1L putatively regulates human embryonic stem cell differentiation into the cardiac lineage. Stem cell research & therapy 20 29631608
2022 DOT1L activity in leukemia cells requires interaction with ubiquitylated H2B that promotes productive nucleosome binding. Cell reports 19 35172132
2022 The Role of DOT1L in Normal and Malignant Hematopoiesis. Frontiers in cell and developmental biology 19 35712672
2022 Combinatorial targeting of a chromatin complex comprising Dot1L, menin and the tyrosine kinase BAZ1B reveals a new therapeutic vulnerability of endocrine therapy-resistant breast cancer. Breast cancer research : BCR 19 35850772
2021 Histone Methyltransferase Dot1L Contributes to RIPK1 Kinase-Dependent Apoptosis in Cerebral Ischemia/Reperfusion. Journal of the American Heart Association 19 34796721
2022 DOT1L regulates MTDH-mediated angiogenesis in triple-negative breast cancer: intermediacy of NF-κB-HIF1α axis. The FEBS journal 18 36017623
2022 SESAME-catalyzed H3T11 phosphorylation inhibits Dot1-catalyzed H3K79me3 to regulate autophagy and telomere silencing. Nature communications 17 36473858
2023 DOT1L activity affects neural stem cell division mode and reduces differentiation and ASNS expression. EMBO reports 16 37382163
2020 Maternal DOT1L is dispensable for mouse development. Scientific reports 16 33244015
2019 The Role of Dot1l in Prenatal and Postnatal Murine Chondrocytes and Trabecular Bone. JBMR plus 16 32083237
2015 Dot1 histone methyltransferases share a distributive mechanism but have highly diverged catalytic properties. Scientific reports 16 25965993
2024 PARP1-DOT1L transcription axis drives acquired resistance to PARP inhibitor in ovarian cancer. Molecular cancer 15 38778348
2023 DOT1L bridges transcription and heterochromatin formation at mammalian pericentromeres. EMBO reports 15 37317657
2022 Design, Synthesis, and Biological Evaluations of DOT1L Peptide Mimetics Targeting the Protein-Protein Interactions between DOT1L and MLL-AF9/MLL-ENL. Journal of medicinal chemistry 15 35612819
2021 Role of Dot1L and H3K79 methylation in regulating somatic hypermutation of immunoglobulin genes. Proceedings of the National Academy of Sciences of the United States of America 15 34253616
2020 Nullifying epigenetic writer DOT1L attenuates neointimal hyperplasia. Atherosclerosis 15 32799103
2020 Dot1l interacts with Zc3h10 to activate Ucp1 and other thermogenic genes. eLife 15 33107819
2017 DOT1L inhibitor improves early development of porcine somatic cell nuclear transfer embryos. PloS one 15 28632762
2023 DOT1L is a barrier to histone acetylation during reprogramming to pluripotency. Science advances 14 37976354
2022 DOT1L Mediated Gene Repression in Extensively Self-Renewing Erythroblasts. Frontiers in genetics 14 35401699
2024 An emerging maestro of immune regulation: how DOT1L orchestrates the harmonies of the immune system. Frontiers in immunology 13 38962004
2021 DOT1L Regulates Thermogenic Adipocyte Differentiation and Function via Modulating H3K79 Methylation. Diabetes 13 33795413
2021 AF10 (MLLT10) prevents somatic cell reprogramming through regulation of DOT1L-mediated H3K79 methylation. Epigenetics & chromatin 13 34215314

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