Affinage

Showing MLLT1 — ENL is a alias.

MLLT1

Protein ENL · UniProt Q03111

Length
559 aa
Mass
62.1 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MLLT1/ENL is a nuclear transcriptional coactivator that couples histone acylation recognition to RNA polymerase II elongation at active genes and super-enhancers (PMID:28241139, PMID:38241700). Its N-terminal YEATS domain reads acetylated and other acylated histone lysines—including KAT6A/MOZ-deposited H3K9ac and the ketone-body mark H3K9β-hydroxybutyrylation—and this reader activity recruits ENL-associated complexes to chromatin to drive elongation (PMID:34853079, PMID:38880495, PMID:39794553). Through its C-terminal intrinsically disordered ANC1 homology domain (AHD), ENL scaffolds a higher-order elongation assembly (EAP/AEP/SEC) by coupled folding upon binding AF4-family proteins, P-TEFb (CDK9/Cyclin T), and the H3K79 methyltransferase DOT1L, and ENL is required for genome-wide H3K79 dimethylation and transcriptional elongation (PMID:17855633, PMID:20153263, PMID:34174329). The same domain alternatively engages PRC1 component CBX8, and these elongation- versus repression-directed interactions are mutually exclusive, allowing ENL to switch between activating and silencing outputs (PMID:11313972, PMID:23623499). Following DNA double-strand breaks, ATM phosphorylates ENL at SQ sites, shifting it toward PRC1/BMI1 to promote local H2A ubiquitination and transcriptional repression near damage (PMID:25921070). ENL's intrinsically disordered regions drive liquid-liquid phase separation that fluidizes elongation-complex condensates required for rapid transcriptional induction (PMID:32270036). In disease, the MLL-ENL fusion constitutively recruits this elongation machinery to MLL targets (Hoxa cluster, Meis1, Myc) to immortalize hematopoietic progenitors and cause leukemia in a YEATS- and AF4-interaction-dependent manner (PMID:9250666, PMID:14701735, PMID:36435883), and recurrent gain-of-function YEATS mutations in Wilms tumour generate aberrant transcriptional condensates that activate MYC and HOX programs (PMID:26635203, PMID:36272410). ENL is genetically essential in MLL-rearranged leukemia and is a validated drug target via YEATS-domain inhibitors that displace it from chromatin (PMID:28241139, PMID:36053276).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1994 High

    Establishing that ENL is itself a transcriptional activator was the first step toward explaining why its fusion partner matters in leukemia; this localized the activity to a conserved C-terminal domain shared with AF9.

    Evidence Deletion mutagenesis with transient reporter assays in lymphoid, myeloid, and yeast cells

    PMID:8080983

    Open questions at the time
    • No molecular mechanism for activation identified
    • No interacting partners defined
  2. 1997 High

    Demonstrating that the ENL moiety is required for HRX-ENL leukemogenesis tied ENL's intrinsic transactivation function directly to oncogenic gain-of-function rather than mere fusion.

    Evidence Retroviral HSC transduction with serial replating and mouse leukemia models using deletion controls

    PMID:9250666

    Open questions at the time
    • Downstream target genes not identified
    • Molecular partners of the ENL domain unknown
  3. 1998 High

    Mapping the transforming activity to two C-terminal helices showed that the same domain governs transcription and transformation, defining a single critical functional module.

    Evidence Structure-function deletion analysis with transformation and reporter assays plus in vitro DNA binding

    PMID:9418860

    Open questions at the time
    • Did not identify the proteins recruited by the helices
    • Non-specific DNA binding role unclear
  4. 2000 High

    Identifying ABI1 as a direct ENL partner connected ENL to another MLL fusion partner, hinting at a shared interaction network.

    Evidence Yeast two-hybrid, far-western, GST pull-down, co-IP with deletion mapping

    PMID:10777208

    Open questions at the time
    • Functional significance of ENL-ABI1 in transformation untested
    • Region distinct from the transformation domain
  5. 2001 High

    Two studies framed ENL as both a Polycomb-linked scaffold and a Myc-dependent transforming agent, foreshadowing its dual repressive/activating roles and downstream effectors.

    Evidence Co-IP/Y2H/far-western for CBX8 interaction; dominant-negative Myc and overexpression epistasis in primary hematopoietic cells

    PMID:11313972 PMID:11522644

    Open questions at the time
    • How a Polycomb-binding protein activates transcription unresolved
    • Direct vs indirect role of Myc unclear
  6. 2004 High

    Defining Hoxa9/Hoxa7/Meis1/Pbx3 as critical MLL-ENL targets and showing Hoxa9+Meis1 substitutes for the fusion established the downstream transcriptional program driving transformation.

    Evidence Inducible MLL-ENL-ER system with microarray, rescue, and Bmi-1 epistasis

    PMID:14701735

    Open questions at the time
    • Mechanism of target gene selection not defined
    • How ENL sustains activation unknown
  7. 2005 High

    Showing ENL binds AF4/AF5q31 through its transformation domain and binds histones via the YEATS domain unified the scaffolding and chromatin-reading functions into one model.

    Evidence Y2H, GST pull-down, co-IP, size exclusion, histone overlay/pulldown, YEATS mutant reporters

    PMID:15856011

    Open questions at the time
    • Specific acyl marks read by YEATS not defined
    • Composition of full complex incomplete
  8. 2007 High

    Purifying the EAP complex containing P-TEFb and DOT1L, and showing ENL knockdown reduces global H3K79me2 and elongation, established ENL as a hub linking acylation reading to elongation and H3K79 methylation.

    Evidence IP-MS, co-IP, in vitro methylase/CTD kinase assays, run-on elongation, shRNA

    PMID:17855633

    Open questions at the time
    • Recruitment cues to specific genes not defined
    • Stoichiometry/architecture of complex unresolved
  9. 2008 Medium

    Demonstrating that re-inserting the MLL PHD finger recruits Cyp33/HDAC1 and blocks immortalization clarified that loss of repressive modules is what licenses constitutive MLL-ENL activation.

    Evidence Domain insertion mutagenesis, co-IP, RT-PCR, serial replating

    PMID:18676843

    Open questions at the time
    • Single-lab domain-insertion model
    • Generalizability across MLL fusions untested
  10. 2010 High

    Defining the AEP higher-order complex and its constitutive hijacking by MLL fusions formalized the mechanistic basis of sustained MLL-target expression and transformation.

    Evidence Reciprocal co-IP, ChIP, hematopoietic transformation assays

    PMID:20153263

    Open questions at the time
    • Dynamics of AEP assembly on chromatin not resolved
    • Distinction from physiological recruitment unclear
  11. 2013 High

    Showing ENL's elongation and CBX8/PRC1 contacts are mutually exclusive provided a molecular switch explaining how a single scaffold toggles between activation and Polycomb repression.

    Evidence Co-IP, in vitro mutual-exclusivity binding, reporter assays, transformation with structure-function mutants

    PMID:23623499

    Open questions at the time
    • Trigger that selects between states in vivo unclear
    • Role of MLL-ENL dimerization not fully resolved
  12. 2014 Medium

    Pinpointing a specific ENL-AFF1 salt bridge as essential for transformation provided an atomic-level target within the leukemogenic interaction.

    Evidence Structure-guided mutagenesis and hematopoietic transformation assay

    PMID:25282333

    Open questions at the time
    • Modeled from paralog structure, not direct ENL structure
    • Single-lab validation
  13. 2015 High

    Two studies extended ENL beyond elongation: ATM phosphorylation switches it to PRC1/BMI1-mediated repression at DSBs, while recurrent Wilms tumour YEATS mutations alter acetyl-histone binding to dysregulate MYC/HOX.

    Evidence Co-IP/phospho/ChIP/ATM assays for DSB response; tumour sequencing and YEATS binding/expression assays for Wilms mutants

    PMID:25921070 PMID:26635203

    Open questions at the time
    • Functional consequence of Wilms mutants inferred from expression in single study
    • How the DSB switch is reversed unknown
  14. 2016 High

    Resolving MLL-ENL targets into DOT1L-dependent promoter-bound (ME5) and P-TEFb-dependent readthrough (ME3) classes revealed mechanistically distinct gene programs with differential drug sensitivities.

    Evidence Nascent RNA-seq, ChIP-seq, and DOT1L/P-TEFb inhibitor treatment

    PMID:27050521

    Open questions at the time
    • Determinants of class assignment unclear
    • Applicability to wild-type ENL targets untested
  15. 2017 High

    A genome-scale CRISPR screen plus targeted degradation established ENL as a non-redundant, YEATS-dependent dependency controlling Pol II initiation and elongation in MLL-AF4 leukemia.

    Evidence CRISPR LOF screen, auxin-inducible degron, ChIP-seq, YEATS point mutants

    PMID:28241139

    Open questions at the time
    • Mechanism distinguishing high-load genes unresolved
    • Physiological (non-leukemic) requirement less defined
  16. 2020 High

    Demonstrating that ENL's IDR drives phase separation of the SEC introduced condensate formation as the physical basis for rapid transcriptional induction and MLL-ENL enhancement.

    Evidence In vitro droplet assays, live-cell imaging, FRAP, IDR mutagenesis, reporters

    PMID:32270036

    Open questions at the time
    • Endogenous-level condensate relevance at native loci not fully shown
    • Contribution to gene specificity unclear
  17. 2021 Medium

    Structural and regulatory studies refined ENL function: the AHD folds upon binding diverse partners, and SIRT2-controlled K469 acetylation in the linker modulates MLL-ENL proliferation and chemoresistance.

    Evidence NMR backbone dynamics of AHD complexes; K469Q mimic and Sirt2 KO in murine AML

    PMID:34174329 PMID:35108652

    Open questions at the time
    • AHD findings consolidated/review-level
    • SIRT2-ENL axis from single lab
  18. 2022 High

    Multiple studies cemented YEATS chromatin reading as the actionable core: cancer hotspot mutations form aberrant condensates, the YEATS domain is retained and essential in patient MLL-ENL leukemia, and YEATS inhibitors (TDI-11055) displace ENL to suppress oncogenic programs.

    Evidence Live-cell imaging/FRAP/ChIP-seq for condensates; mouse leukemia YEATS deletion/point mutants; ChIP-seq/RNA-seq/CRISPR-resistance/PDX for inhibitor

    PMID:36053276 PMID:36272410 PMID:36435883

    Open questions at the time
    • Long-term resistance landscape to YEATS inhibition incomplete
    • Condensate role in non-mutant contexts less clear
  19. 2022 High

    Identifying KAT6A-deposited H3K9ac as the mark read by the ENL YEATS domain defined an upstream writer-reader module initiating elongation in AML.

    Evidence CRISPR differentiation screen, co-IP, ChIP-seq, KAT6A inhibition, YEATS binding assays

    PMID:34853079

    Open questions at the time
    • Other acyltransferases feeding ENL not fully mapped
    • Promoter selectivity determinants unresolved
  20. 2024 High

    Later studies broadened ENL's chromatin biology: it governs super-enhancers via FACT recruitment and BRD4, reads the ketone-body mark H3K9bhb, and its ortholog's crotonylation-reader function modulates neuronal aging.

    Evidence AID depletion/ChIP-seq/FACT co-IP for SEs; chemical proteomics/CUT&Tag for H3K9bhb; Drosophila pan-neuronal RNAi with aging/oxidative readouts

    PMID:38241700 PMID:38880495 PMID:39405796

    Open questions at the time
    • Mammalian neuronal/aging role of ENL untested
    • Interplay of distinct acyl marks at shared loci unresolved
  21. 2024 High

    Structural resolution of the multivalent ENL-MOZ assembly showed ENL's ET domain and YEATS domain together engage MOZ's IDR through CBP/p300-dependent acetylation, defining how an acyltransferase recruits ENL to active promoters.

    Evidence Structural studies, co-IP, ChIP-seq, domain mutagenesis, binding assays

    PMID:39794553

    Open questions at the time
    • Functional consequence of ENL-MOZ coupling in disease not fully tested
    • Relationship to KAT6A module unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ENL integrates distinct acyl-mark inputs (H3K9ac, crotonyl, β-hydroxybutyryl) and switches between elongation-promoting condensates and PRC1-mediated repression to achieve gene- and context-specific outputs in normal physiology remains unresolved.
  • No unified model of mark-specific recruitment in normal cells
  • Physiological role of phase separation at endogenous loci unclear
  • Mammalian developmental/neuronal functions beyond embryonic lethality undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 5 GO:0060090 molecular adaptor activity 4 GO:0140110 transcription regulator activity 3
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3 R-HSA-4839726 Chromatin organization 3 R-HSA-73894 DNA Repair 1
Partners
ABI1AFF1/AF4AFF4BMI1CBX8CDK9DOT1LKAT6A/MOZ
Complex memberships
AEP/EAP super elongation complexPRC1 (via CBX8/BMI1)

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 ENL (MLLT1) is a nuclear protein with transcriptional transactivation activity in both lymphoid and myeloid cells, and in yeast. Deletion mutagenesis localized the minimal transcriptional activation domain to the C-terminal 90 amino acids of ENL, a region highly conserved with AF9 that is retained in all HRX-ENL and HRX-AF9 fusion proteins. Deletion mutagenesis, transient reporter gene assays in lymphoid and myeloid cell lines and yeast Blood High 8080983
1998 The oncogenic capacity of HRX-ENL requires the transcriptional transactivation activity contributed by the C-terminal 84 amino acids of ENL (encoding two conserved helical structures). Deletions of either helix completely abrogated both transcriptional activation and in vitro myeloid transforming activity. The MLL methyltransferase homology domain was shown to bind DNA non-sequence specifically in vitro. Structure-function deletion analysis, in vitro myeloid immortalization assay, transcriptional reporter assays, in vitro DNA binding assay Molecular and cellular biology High 9418860
1997 HRX-ENL fusion protein directly immortalizes a myelomonocytic precursor and induces myeloid leukemia in mice. Wild-type ENL alone or HRX-ENL lacking the ENL component did not transform cells, establishing that the ENL moiety is required for the gain-of-function leukemogenic activity. Retroviral transduction of hematopoietic stem cells, serial replating colony assay, syngeneic and SCID mouse leukemia model The EMBO journal High 9250666
2001 The C-terminal domain of ENL (the same region required for transformation) directly recruits human Polycomb 3 (hPc3/CBX8) via a protein-protein interaction. This was demonstrated by yeast two-hybrid, GST pull-down, far-western blot, mutual co-immunoprecipitation from cell extracts, and co-localization of fluorescently tagged proteins in nuclear dot patterns in living cells. Yeast two-hybrid, GST pull-down, far-western blot, co-immunoprecipitation, live-cell fluorescence co-localization Oncogene High 11313972
2005 ENL directly interacts with AF4 and AF5q31 (and a fragment of AF10) through its C-terminus (also the transformation-essential domain). The ENL/AF4 interaction was confirmed by GST pull-down and mutual co-immunoprecipitation. Both proteins co-localized in nuclear speckles in vivo and co-eluted on sizing columns with Polycomb3, suggesting a multiprotein complex. The YEATS domain of ENL is essential for transcriptional activation from a reporter construct. ENL binds histones H3 and H1 in a YEATS domain-dependent manner. Yeast two-hybrid, GST pull-down, co-immunoprecipitation, co-localization, size exclusion chromatography, histone overlay and pull-down assays, reporter assay with YEATS domain mutants Oncogene High 15856011
2007 ENL associates in vivo with a complex (EAP) containing pTEFb (CDK9/Cyclin T), DOT1L (histone H3K79 methyltransferase), AF4, AF5q31, LAF4, and Polycomb members (RING1, CBX8, BCoR). Purified EAP displayed H3K79-specific methylase activity and robust RNA Pol II CTD kinase function. ENL knockdown reduced genome-wide H3K79 dimethylation and global transcriptional elongation. DOT1L recruitment to ENL was important for transformation by MLL-ENL. Immunopurification + mass spectrometry, co-immunoprecipitation, yeast two-hybrid, GST pull-down, co-localization, in vitro histone methylase assay, RNA Pol II CTD kinase assay, global run-on elongation assay, shRNA knockdown Blood High 17855633
2010 ENL and AF9 family proteins together with AF4 family proteins form a higher-order complex (AEP) containing P-TEFb. AEP is normally recruited to MLL-target chromatin to facilitate transcription, and MLL oncoproteins fused with AEP components constitutively form hybrid complexes causing sustained target gene expression and hematopoietic progenitor transformation. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), hematopoietic progenitor transformation assay Cancer cell High 20153263
2015 In response to DNA double-strand breaks (DSBs), ENL is phosphorylated by ATM at conserved SQ sites. This phosphorylation increases ENL's interaction with PRC1 via BMI1, promoting enrichment of PRC1 at transcription elongation sites near DSBs, leading to H2A ubiquitination and transcriptional repression. ENL SQ sites and BMI1 are required for KU70 accumulation at DSBs near active transcription. Co-immunoprecipitation, phosphorylation assays, ChIP, siRNA knockdown, DSB survival assays, ATM kinase assay Molecular cell High 25921070
2017 The YEATS chromatin-reader domain of ENL is essential for ENL-dependent leukaemic growth. Acute loss of ENL (via chemical genetic targeted degradation) suppressed initiation and elongation of RNA polymerase II at active genes genome-wide, with pronounced effects at genes with disproportionate ENL load. CRISPR loss-of-function screen identified ENL as specifically required for proliferation in MLL-AF4-positive leukemia in vitro and in vivo. CRISPR-Cas9 genome-scale loss-of-function screen, auxin-inducible degron targeted protein degradation, ChIP-seq, RNA Pol II elongation assays, YEATS domain point mutagenesis Nature High 28241139
2015 Recurrent gain-of-function mutations in the YEATS domain of MLLT1 (ENL) in Wilms tumours alter binding to acetylated histone tails. Mutant MLLT1 tumours show increased MYC expression and HOX dysregulation. Genomic sequencing of Wilms tumour samples, biochemical binding assays of mutant vs wild-type YEATS domain to acetylated histone tails, gene expression analysis Nature communications Medium 26635203
2022 Cancer-associated hotspot mutations in the ENL YEATS domain trigger aberrant transcriptional condensates at native genomic targets. Mechanistically, mutation-induced structural changes in the YEATS domain, ENL's two disordered regions of opposing charges, and incorporation of extrinsic elongation factors are all required for condensate formation. Extensive mutagenesis establishes condensate formation as a driver of oncogenic gene activation. Fluorescence live-cell imaging, FRAP, mutagenesis, ChIP-seq, gene expression analysis, structural analysis Molecular cell High 36272410
2020 ENL, or its intrinsically disordered region (IDR) alone, is sufficient to initiate liquid-liquid phase separation and liquid droplet formation of the super elongation complex (SEC). AFF4 cooperates with ENL in fluidizing SEC droplets. SEC droplets form rapidly upon serum exposure and are required for rapid transcriptional induction. MLL-ENL fusion boosts SEC phase separation compared to wild-type ENL. In vitro droplet formation assays, live-cell fluorescence imaging, FRAP, transcriptional reporter assays, IDR deletion/mutagenesis Science advances High 32270036
2013 ENL serves as a scaffold that contacts the elongation machinery AND Polycomb repressive complex 1 (PRC1) component CBX8, but these interactions are mutually exclusive in vitro. CBX8 inhibits transcriptional elongation in a reporter assay, and this is neutralized by direct ENL-CBX8 association. CBX8-binding-defective MLL-ENL cannot fully activate leukemogenic gene loci. MLL-ENL also dimerizes as a neomorphic activity that may augment Polycomb inhibition. Biochemical co-immunoprecipitation, in vitro binding (mutual exclusivity), transcriptional reporter assay, mutagenesis, transformation assay in hematopoietic progenitors Cell reports High 23623499
2000 ENL directly interacts with ABI1 (c-Abl interactor 1, itself fused to MLL in t(10;11) leukemia). Identified by yeast two-hybrid screen; verified by far-western blot, GST pull-down, and co-immunoprecipitation from cell extracts. Structure-function analysis identified an internal region of ENL and a composite SH3-containing motif of ABI1 as mutual binding partners. Yeast two-hybrid, far-western blot, GST pull-down, co-immunoprecipitation, deletion mapping Oncogene High 10777208
2008 Insertion of the third PHD finger of MLL into MLL-ENL allows recruitment of Cyp33 and subsequently HDAC1 to the fusion protein, mediates HOX gene downregulation in a Cyp33-dependent manner, and blocks hematopoietic stem cell immortalization by MLL-ENL. Loss of the PHD fingers in MLL fusion proteins is thus necessary for the constitutive transactivation that drives leukemogenesis. Co-immunoprecipitation, gene expression analysis (RT-PCR), serial replating colony assay (immortalization), domain insertion mutagenesis Cancer research Medium 18676843
2014 A specific salt bridge formed by a pair of amino acids between MLLT1/ENL and AFF family proteins (AF4/AFF1) is critically important for MLL-ENL-mediated transformation of hematopoietic progenitor cells. Mutational disruption of this salt bridge abrogates transformation. Mutational analysis, hematopoietic progenitor cell transformation assay, structural modeling informed by MLLT3-AFF1 complex structure Leukemia research Medium 25282333
2022 ENL YEATS domain displaces from chromatin upon treatment with the small-molecule inhibitor TDI-11055 (blocking acylated histone interaction), rapidly decreasing chromatin occupancy of ENL-associated complexes and impairing transcription elongation, leading to suppression of oncogenic gene programs and induction of differentiation. A CRISPR-Cas9 mutagenesis screen identified an ENL mutation conferring resistance, validating on-target chromatin displacement mechanism. ChIP-seq, RNA-seq, CRISPR resistance screen, patient-derived xenograft in vivo model, biochemical YEATS domain binding assay Cancer discovery High 36053276
2022 KAT6A-catalyzed H3K9 acetylation at promoters is bound by the ENL YEATS domain, initiating a transcriptional control module in which ENL cooperates with a network of chromatin factors to induce transcriptional elongation. KAT6A inhibition phenocopies ENL loss in AML. CRISPR differentiation screen, co-immunoprecipitation, ChIP-seq, KAT6A inhibition, ENL YEATS domain binding assays Cancer discovery High 34853079
2024 ENL YEATS domain binds histone H3K9β-hydroxybutyrylation (H3K9bhb), a new histone acyl mark. Chemical proteomics with multivalent photoaffinity probes identified ENL as a novel H3K9bhb reader. CUT&Tag confirmed co-localization of ENL with H3K9bhb at promoters. Structure-based mutation disrupting H3K9bhb-ENL interaction suppressed MYC-driven cell proliferation. Chemical proteomics (photoaffinity probes), biochemical binding assay, CUT&Tag chromatin profiling, structure-based mutagenesis, gene expression analysis Nucleic acids research High 38880495
2025 ENL associates with the acetyltransferase MOZ through a multivalent assembly. The extraterminal (ET) domain of ENL recognizes the canonical ET-binding motif in the intrinsically disordered region (IDR) of MOZ. Additionally, the YEATS domain of ENL binds to acetylation sites within the MOZ IDR that are generated by CBP/p300 acetyltransferase activity. Genomic analysis showed ENL and MOZ co-occupy active promoters, and MOZ recruits ENL to its gene targets. Structural studies, co-immunoprecipitation, ChIP-seq, domain mutagenesis, biochemical binding assays Nature structural & molecular biology High 39794553
2001 MLL-ENL-induced block of myelomonocytic cell differentiation requires the oncoprotein Myc. Co-transduction of dominant-negative Myc neutralized MLL-ENL transformation, while constitutive Myc expression cooperated with MLL-ENL to cause irreversible maturation arrest. G-CSF-mediated differentiation was accompanied by c-myc downregulation. Retroviral co-transduction, dominant-negative Myc expression, gene expression analysis, colony assay, differentiation assay with G-CSF Cancer research Medium 11522644
2004 MLL-ENL activates Hoxa9, Hoxa7, Meis1, and Pbx3 expression as critical downstream targets. Enforced expression of Hoxa9 combined with Meis1 was sufficient to substitute for MLL-ENL function and maintain continuous proliferation and differentiation arrest. Overexpression of the Hox repressor Bmi-1 inhibited MLL-ENL growth-transforming activity. Inducible MLL-ENL-ERtm system, microarray analysis, retroviral overexpression, tamoxifen withdrawal differentiation assay, Bmi-1 overexpression epistasis Molecular and cellular biology High 14701735
2016 MLL-ENL directly targets two functionally distinct gene groups: ME5 genes bound at promoters, dependent on DOT1L-mediated H3K79 methylation, encoding transcription factors including Hox genes; and ME3 genes with MLL-ENL accumulation beyond the termination site, dependent on P-TEFb-mediated RNA Pol II phosphorylation, encoding proteins in RNA biology and ribosome assembly. These groups show differential sensitivity to DOT1L and P-TEFb inhibitors. Nascent RNA-seq, ChIP-seq, small molecule inhibitor treatment (DOT1L and P-TEFb inhibitors), transformed cell line analysis Cell reports High 27050521
2022 The YEATS domain within the MLL-ENL fusion protein is retained in 84.1% of MLL-ENL patient samples and is crucial for MLL-ENL-mediated leukemogenesis in mouse models. Deletion of the YEATS domain impaired MLL-ENL binding and decreased expression of pro-leukemic genes including Eya1 and Meis1. Point mutations disrupting YEATS domain binding to acetylated histones decreased leukemic stem cell frequency and increased leukemia latency. Retroviral mouse leukemia model, YEATS domain deletion and point mutagenesis, ChIP, gene expression analysis, limiting dilution transplantation for stem cell frequency Leukemia High 36435883
2021 SIRT2 deacetylase regulates MLL-ENL-driven AML. A conserved lysine K469 in the ENL linker region controls cell cycle progression and chemotherapy resistance; substitution with an acetylated mimic (K469Q) abolished MLL-ENL's ability to suppress proliferation and promote chemo-resistance. SIRT2 deletion promoted proliferation and sensitized MLL-ENL AML cells to chemotherapy. Murine MLL-ENL AML model, K469Q acetylation mimic mutagenesis, Sirt2 knockout, cell cycle analysis, chemotherapy sensitivity assays Biochemical and biophysical research communications Medium 35108652
2021 The intrinsically disordered C-terminal ANC1 homology domain (AHD) of ENL/MLLT1 undergoes coupled binding and folding upon interaction with partner proteins including AF4, DOT1L, BCOR, and CBX8. NMR backbone dynamics studies of the complexes revealed dynamics-dependent function of the AHD. NMR spectroscopy, binding assays, structural analysis of AHD complexes Journal of molecular biology Medium 34174329
2024 ENL occupies the majority of super-enhancers (SEs) with higher preference over typical enhancers in a manner dependent on its ability to bind acetylated histones (YEATS domain). Rapid ENL depletion decommissions SEs, repressing SE-controlled oncogenes such as MYC. ENL interacts with the histone chaperone FACT complex and is required for FACT deposition over cis-regulatory elements; ENL's transcriptional control is regulated by BRD4. Auxin-inducible degron (AID) rapid depletion, ChIP-seq, FACT co-immunoprecipitation, ENL YEATS mutants, BRD4 inhibition, colorectal cancer in vivo model Cancer research High 38241700
2002 Targeted disruption of murine Mllt1 leads to embryonic lethality prior to embryonic day 8.5, indicating an essential role for MLLT1 in early embryonic development. Gene targeting/knockout in mice, developmental phenotype analysis Blood cells, molecules & diseases Medium 12367585
2024 In Drosophila, pan-neuronal knockdown of dENL/AF9 (the ENL/AF9 ortholog) extends lifespan and enhances fitness during aging, including improved sleep and locomotion. This is associated with upregulation of catalase, reduced malondialdehyde, and enhanced oxidative stress tolerance, revealing a role for the histone acylation (crotonylation) reader function of ENL/AF9 in neuronal aging. Pan-neuronal RNAi knockdown in Drosophila, lifespan analysis, locomotion assays, sleep analysis, oxidative stress assays, gene expression analysis Neurobiology of aging Medium 39405796

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Immortalization and leukemic transformation of a myelomonocytic precursor by retrovirally transduced HRX-ENL. The EMBO journal 355 9250666
2007 A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification. Blood 331 17855633
2010 A higher-order complex containing AF4 and ENL family proteins with P-TEFb facilitates oncogenic and physiologic MLL-dependent transcription. Cancer cell 306 20153263
2004 Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization. Molecular and cellular biology 273 14701735
2017 Transcription control by the ENL YEATS domain in acute leukaemia. Nature 245 28241139
1998 The oncogenic capacity of HRX-ENL requires the transcriptional transactivation activity of ENL and the DNA binding motifs of HRX. Molecular and cellular biology 207 9418860
1996 TFG/TAF30/ANC1, a component of the yeast SWI/SNF complex that is similar to the leukemogenic proteins ENL and AF-9. Molecular and cellular biology 143 8668146
2015 Transcriptional elongation factor ENL phosphorylated by ATM recruits polycomb and switches off transcription for DSB repair. Molecular cell 142 25921070
1994 A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related to AF-4, AF-9 nor ENL. Oncogene 118 8134107
1994 ENL, the gene fused with HRX in t(11;19) leukemias, encodes a nuclear protein with transcriptional activation potential in lymphoid and myeloid cells. Blood 116 8080983
2005 The eleven-nineteen-leukemia protein ENL connects nuclear MLL fusion partners with chromatin. Oncogene 101 15856011
1993 MLLT3 gene on 9p22 involved in t(9;11) leukemia encodes a serine/proline rich protein homologous to MLLT1 on 19p13. Oncogene 99 8414510
2022 KAT6A and ENL Form an Epigenetic Transcriptional Control Module to Drive Critical Leukemogenic Gene-Expression Programs. Cancer discovery 86 34853079
1999 Cytokine mRNA expression in leprosy: a possible role for interferon-gamma and interleukin-12 in reactions (RR and ENL). Scandinavian journal of immunology 81 10564558
1993 Two distinct portions of LTG19/ENL at 19p13 are involved in t(11;19) leukemia. Oncogene 80 8378076
2015 MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours. Nature communications 77 26635203
1998 Pentoxifylline decreases in vivo and in vitro tumour necrosis factor-alpha (TNF-alpha) production in lepromatous leprosy patients with erythema nodosum leprosum (ENL). Clinical and experimental immunology 74 9486396
2021 Chemical Inhibition of ENL/AF9 YEATS Domains in Acute Leukemia. ACS central science 73 34079898
1999 Childhood acute lymphoblastic leukemia with the MLL-ENL fusion and t(11;19)(q23;p13.3) translocation. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 73 10458233
2022 Hotspot mutations in the structured ENL YEATS domain link aberrant transcriptional condensates and cancer. Molecular cell 68 36272410
2010 MLL-AF9 and MLL-ENL alter the dynamic association of transcriptional regulators with genes critical for leukemia. Experimental hematology 67 20854876
2020 ENL initiates multivalent phase separation of the super elongation complex (SEC) in controlling rapid transcriptional activation. Science advances 66 32270036
2009 Homing and invasiveness of MLL/ENL leukemic cells is regulated by MEF2C. Blood 65 19584403
2017 CRISPR-Cas9-induced t(11;19)/MLL-ENL translocations initiate leukemia in human hematopoietic progenitor cells in vivo. Haematologica 63 28572162
2005 Continuous MLL-ENL expression is necessary to establish a "Hox Code" and maintain immortalization of hematopoietic progenitor cells. Cancer research 57 16230385
2001 The ENL moiety of the childhood leukemia-associated MLL-ENL oncoprotein recruits human Polycomb 3. Oncogene 57 11313972
2012 DNA damage response and inflammatory signaling limit the MLL-ENL-induced leukemogenesis in vivo. Cancer cell 56 22516260
2001 MLL-ENL causes a reversible and myc-dependent block of myelomonocytic cell differentiation. Cancer research 53 11522644
2008 Loss of MLL PHD finger 3 is necessary for MLL-ENL-induced hematopoietic stem cell immortalization. Cancer research 51 18676843
2022 Small-Molecule Inhibition of the Acyl-Lysine Reader ENL as a Strategy against Acute Myeloid Leukemia. Cancer discovery 48 36053276
2014 Hematopoietic stem cells are intrinsically protected against MLL-ENL-mediated transformation. Cell reports 47 25456127
2018 Discovery of a Selective Inhibitor for the YEATS Domains of ENL/AF9. SLAS discovery : advancing life sciences R & D 44 30359161
2013 MLL-ENL inhibits polycomb repressive complex 1 to achieve efficient transformation of hematopoietic cells. Cell reports 43 23623499
2003 The oncoprotein MLL-ENL disturbs hematopoietic lineage determination and transforms a biphenotypic lymphoid/myeloid cell. Oncogene 43 12642866
2016 Leukemogenic MLL-ENL Fusions Induce Alternative Chromatin States to Drive a Functionally Dichotomous Group of Target Genes. Cell reports 41 27050521
1999 The leukemogenic fusion of MLL with ENL creates a novel transcriptional transactivator. Leukemia 37 10516753
2021 The Intrinsically Disordered Proteins MLLT3 (AF9) and MLLT1 (ENL) - Multimodal Transcriptional Switches With Roles in Normal Hematopoiesis, MLL Fusion Leukemia, and Kidney Cancer. Journal of molecular biology 36 34174329
2021 Discovery of Selective Small-Molecule Inhibitors for the ENL YEATS Domain. Journal of medicinal chemistry 34 34279931
2012 Lessons of leprosy: the emergence of TH17 cytokines during type II reactions (ENL) is teaching us about T-cell plasticity. Journal of drugs in dermatology : JDD 34 22527432
1995 Clinical and histological discrepancies in diagnosis of ENL reactions classified by assessment of acute phase proteins SAA and CRP. International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association 34 7602217
2020 Cell-Based Ligand Discovery for the ENL YEATS Domain. ACS chemical biology 31 32176478
2018 Structure-Based Approach toward Identification of Inhibitory Fragments for Eleven-Nineteen-Leukemia Protein (ENL). Journal of medicinal chemistry 28 30407816
2018 Peptidomimetics for Targeting Protein-Protein Interactions between DOT1L and MLL Oncofusion Proteins AF9 and ENL. ACS medicinal chemistry letters 26 30258537
2000 ENL, the MLL fusion partner in t(11;19), binds to the c-Abl interactor protein 1 (ABI1) that is fused to MLL in t(10;11)+. Oncogene 25 10777208
2019 The efficiency of murine MLL-ENL-driven leukemia initiation changes with age and peaks during neonatal development. Blood advances 24 31405949
2008 Acute myeloid leukemia induced by MLL-ENL is cured by oncogene ablation despite acquisition of complex genetic abnormalities. Blood 24 19029444
2021 HBO1-MLL interaction promotes AF4/ENL/P-TEFb-mediated leukemogenesis. eLife 23 34431785
2019 Structural Insights into Interaction Mechanisms of Alternative Piperazine-urea YEATS Domain Binders in MLLT1. ACS medicinal chemistry letters 22 31857843
2018 ENL: structure, function, and roles in hematopoiesis and acute myeloid leukemia. Cellular and molecular life sciences : CMLS 21 30066088
2015 KMT2A (MLL)-MLLT1 rearrangement in blastic plasmacytoid dendritic cell neoplasm. Cancer genetics 19 26164398
2002 The leukemia-associated gene Mllt1/ENL: characterization of a murine homolog and demonstration of an essential role in embryonic development. Blood cells, molecules & diseases 19 12367585
2018 A Novel Inducible Mouse Model of MLL-ENL-driven Mixed-lineage Acute Leukemia. HemaSphere 18 31723780
2007 Leukaemia lineage specification caused by cell-specific Mll-Enl translocations. Oncogene 17 17906700
2006 Simultaneous localization of MLL, AF4 and ENL genes in interphase nuclei by 3D-FISH: MLL translocation revisited. BMC cancer 17 16433901
2021 Tip60 activates Hoxa9 and Meis1 expression through acetylation of H2A.Z, promoting MLL-AF10 and MLL-ENL acute myeloid leukemia. Leukemia 16 33967269
2017 Does the enterolactone (ENL) affect fatty acid transporters and lipid metabolism in liver? Nutrition & metabolism 16 29158770
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
2023 miR-122-5p Promotes Peripheral and Central Nervous System Inflammation in a Mouse Model of Intracerebral Hemorrhage via Disruption of the MLLT1/PI3K/AKT Signaling. Neurochemical research 14 37594575
2024 Targeting the Epigenetic Reader ENL Inhibits Super-Enhancer-Driven Oncogenic Transcription and Synergizes with BET Inhibition to Suppress Tumor Progression. Cancer research 13 38241700
2007 Analysis of acute leukemias with MLL/ENL fusion transcripts: identification of two novel breakpoints in ENL. American journal of clinical pathology 13 17145626
2002 MLL-ENL cooperates with SCF to transform primary avian multipotent cells. The EMBO journal 13 12169632
1996 Alterations in serum lipids in lepromatous leprosy patients with and without ENL reactions and their relationship to acute phase proteins. International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association 13 8690968
2024 ENL reads histone β-hydroxybutyrylation to modulate gene transcription. Nucleic acids research 12 38880495
2017 MLL-ENL-mediated leukemia initiation at the interface of lymphoid commitment. Oncogene 12 28068328
2006 Establishment of a myeloid leukemia cell line, TRL-01, with MLL-ENL fusion gene. Cancer genetics and cytogenetics 12 16875930
1996 MLL/ENL fusion in congenital acute lymphoblastic leukemia with a unique t(11;18;19). Cancer genetics and cytogenetics 12 8640717
2022 The ENL YEATS epigenetic reader domain critically links MLL-ENL to leukemic stem cell frequency in t(11;19) Leukemia. Leukemia 11 36435883
2016 Collaboration of MLLT1/ENL, Polycomb and ATM for transcription and genome integrity. Nucleus (Austin, Tex.) 11 27310306
2010 Three-way translocation involving MLL, MLLT1, and a novel third partner, NRXN1, in a patient with acute lymphoblastic leukemia and t(2;19;11) (p12;p13.3;q23). Cancer genetics and cytogenetics 11 20113834
2013 In vivo eradication of MLL/ENL leukemia cells by NK cells in the absence of adaptive immunity. Leukemia 10 24336127
2024 Single-cell multiomics reveals ENL mutation perturbs kidney developmental trajectory by rewiring gene regulatory landscape. Nature communications 9 39009564
1996 Selective decrease of M. leprae-specific IgG1 and IgG3 antibodies in leprosy patients associated with ENL. International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association 9 8690967
2023 Design, synthesis of novel benzimidazole derivatives as ENL inhibitors suppressing leukemia cells viability via downregulating the expression of MYC. European journal of medicinal chemistry 8 36645983
2023 Genomic characterization of Mycobacterium lepromatosis from ENL patients from India. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 8 38056703
2022 Spiroarborin, an ent-Clerodane Homodimer from Callicarpa arborea as an Inhibitor of the Eleven-Nineteen Leukemia (ENL) Protein by Targeting the YEATS Domain. Journal of natural products 8 35029993
2024 Lead Optimization of Small Molecule ENL YEATS Inhibitors to Enable In Vivo Studies: Discovery of TDI-11055. ACS medicinal chemistry letters 7 38628784
2022 SIRT2 regulates proliferation and chemotherapy response of MLL-ENL-driven acute myeloid leukemia. Biochemical and biophysical research communications 7 35108652
2020 Development of embryonic and adult leukemia mouse models driven by MLL-ENL translocation. Experimental hematology 7 32437911
2014 Importance of a specific amino acid pairing for murine MLL leukemias driven by MLLT1/3 or AFF1/4. Leukemia research 7 25282333
2010 Mixed phenotype acute leukemia with t(11;19)(q23;p13.3)/ MLL-MLLT1(ENL), B/T-lymphoid type: A first case report. American journal of hematology 7 20513125
2006 The mechanism of hematopoietic progenitor cell immortalization by MLL-ENL. Cell cycle (Georgetown, Tex.) 7 16479159
1998 Antisense oligodeoxyribonucleotide against the MLL-LTG19 chimeric transcript inhibits cell growth and induces apoptosis in cells of an infantile leukemia cell line carrying the t(11;19) chromosomal translocation. Cancer research 7 9731482
1996 Immunological status of ENL (erythema nodosum leprosum) patients: its relationship to bacterial load and levels of circulating IL-2R. Revista do Instituto de Medicina Tropical de Sao Paulo 7 9071029
2023 Circvrk1 downregulation attenuates brain microvascular endothelial cell damage induced by oxygen-glucose deprivation through modulating the miR-150-5p/MLLT1 axis. Experimental brain research 6 36735043
2023 The YEATS domain epigenetic reader proteins ENL and AF9 and their therapeutic value in leukemia. Experimental hematology 6 37295550
2020 Myeloid transformation by MLL-ENL depends strictly on C/EBP. Life science alliance 6 33144337
2025 A multivalent engagement of ENL with MOZ. Nature structural & molecular biology 5 39794553
2023 Discovery, Structure-Activity Relationship and In Vitro Anticancer Activity of Small-Molecule Inhibitors of the Protein-Protein Interactions between AF9/ENL and AF4 or DOT1L. Cancers 5 37958457
2011 A case of therapy-related acute lymphoblastic leukemia with t(11;19)(q23;p13.3) and MLL/MLLT1 gene rearrangement. The Korean journal of laboratory medicine 5 21239865
2011 Molecular findings in childhood leukemia in Brazil: high frequency of MLL-ENL Fusion/t(11;19) in infant leukemia. Journal of pediatric hematology/oncology 5 21436736
2011 Clinical outcome and monitoring of minimal residual disease in patients with acute lymphoblastic leukemia expressing the MLL/ENL fusion gene. American journal of hematology 5 21953510
2024 The histone acylation reader ENL/AF9 regulates aging in Drosophila melanogaster. Neurobiology of aging 4 39405796
2022 Exome sequencing of glioblastoma-derived cancer stem cells reveals rare clinically relevant frameshift deletion in MLLT1 gene. Cancer cell international 4 34996478
2022 Down-regulation of MLLT1 super elongation complex subunit impairs the anti-tumor activity of natural killer cells in esophageal cancer. Immunobiology 4 35763909
2020 Exploitable metabolic dependencies in MLL-ENL-induced leukemia. Blood advances 4 32766858
2020 Long noncoding RNA MEG3 contributes to dysfunction of brain microvascular endothelial cells after intracerebral hemorrhage by regulating the miR-1930-5p/Mllt1 axis. Brain research bulletin 4 33127454
2014 An AF9/ENL-targted peptide with therapeutic potential in mixed lineage leukemias. Journal of experimental therapeutics & oncology 4 25509985
2008 Preclinical modeling of cytosine arabinoside response in Mll-Enl translocator mouse leukemias. Molecular cancer therapeutics 4 18347158
2024 Myeloid Targeted Human MLL-ENL and MLL-AF9 Induces cdk9 and bcl2 Expression in Zebrafish Embryos. PLoS genetics 3 38829886
2014 Identification of a novel isoform of the leukemia-associated MLLT1 (ENL/LTG19) protein. Gene expression patterns : GEP 3 25481096

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