Affinage

LYL1

Protein lyl-1 · UniProt P12980

Audit flag: ungrounded claim
Length
280 aa
Mass
29.9 kDa
Annotated
2026-06-10
41 papers in source corpus 28 papers cited in narrative 27 extracted findings
Cross-family judge faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LYL1 encodes a basic helix-loop-helix (bHLH) transcription factor that orchestrates hematopoietic and vascular gene programs by nucleating multiprotein transcriptional complexes on E-box and composite DNA elements (PMID:2752424, PMID:8628307, PMID:22792348). It heterodimerizes with the E2A proteins E12/E47 through its HLH motif to bind a preferred E-box sequence distinct from the E2A homodimer site, and ectopic LYL1 sequesters E2A to inhibit E2A/HEB regulatory activity (PMID:8628307, PMID:17486074). Within the LMO2–GATA2 framework, LYL1 assembles LYL1–LYL1 or LYL1–TAL1 dimers onto E-box–GATA composite elements to directly activate targets such as ANGIOPOIETIN-2, and in t(8;21) AML it is required for assembly of the larger AETFC complex (AML1-ETO, CBFβ, HEB, E2A, LMO2, LDB1) where it recruits the coactivator CARM1 to active enhancers (PMID:22792348, PMID:36215477). LYL1 also engages partners beyond bHLH networks: it binds NF-κB1 p105 via its bHLH motif to repress NF-κB-dependent transcription, and cooperates with CREB1 (recruiting p300/CBP) to activate promoters including Id1 and STMN1 (PMID:10023675, PMID:18160048, PMID:23000483). In vivo, LYL1 is required—redundantly with SCL—for adult HSC maintenance, B- and T-lymphoid differentiation via progenitor generation and the target Gfi1, primitive erythropoiesis through GATA1, and megakaryopoiesis/platelet production (PMID:16514064, PMID:19200805, PMID:22404772, PMID:22772404, PMID:30185409, PMID:31300405). LYL1 additionally drives postnatal vascular maturation and endothelial barrier integrity through the ARHGAP21/24–RhoA/Rap1–VE-cadherin axis (PMID:20418284, PMID:24532287). Its oncogenic deregulation in T-ALL—originally defined by a t(7;19) translocation—underlies LMO2- and NUP98-HOXD13-driven thymocyte self-renewal and leukemia, for which LYL1 is specifically required (PMID:2752424, PMID:23926305, PMID:30700838). LYL1 protein levels are limited by proteasomal degradation through an N-terminal PEST motif (PMID:20844761).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1989 High

    Establishing LYL1 as an HLH-motif gene disrupted by a recurrent T-ALL translocation defined it as a candidate oncogenic transcription factor.

    Evidence Molecular cloning and sequence analysis of a t(7;19) breakpoint in T-cell ALL

    PMID:2752424

    Open questions at the time
    • Did not establish DNA-binding partners or target genes
    • Mechanism of translocation-driven activation unresolved
  2. 1991 High

    Cross-species conservation and lineage-restricted expression positioned LYL1 as a regulator of hematopoietic differentiation rather than a ubiquitous factor.

    Evidence cDNA cloning, Northern blot, and expression profiling in lymphoid cell lines

    PMID:2067848

    Open questions at the time
    • Expression correlation does not establish functional requirement
    • No target genes identified
  3. 1996 High

    Identifying E2A heterodimerization and a distinct DNA-binding preference defined the biochemical basis of LYL1 transcriptional activity.

    Evidence Yeast two-hybrid, in vitro interaction, endogenous co-IP, and PCR-assisted site selection

    PMID:8628307

    Open questions at the time
    • In vivo target genes of LYL1-E2A not defined
    • Functional output of the heterodimer unaddressed
  4. 1999 High

    Discovery of a bHLH-dependent LYL1–p105 interaction revealed a non-canonical, DNA-binding-independent route by which LYL1 represses NF-κB signaling.

    Evidence Yeast two-hybrid, in vitro binding, mammalian co-IP, and luciferase reporter in a T-cell line

    PMID:10023675

    Open questions at the time
    • Physiological context of NF-κB repression in vivo unestablished
    • Whether this contributes to leukemogenesis unknown
  5. 2003 Medium

    Defining GATA2/Ets occupancy of the LYL1 promoter placed LYL1 within the core hematopoietic/endothelial transcriptional regulatory hierarchy.

    Evidence Comparative genomics, transgenic reporters, and ChIP in myeloid progenitors

    PMID:12659809

    Open questions at the time
    • Upstream regulators do not reveal LYL1's own targets
    • Functional requirement not tested
  6. 2005 Medium

    Gain-of-function differentiation phenotypes implicated LYL1 in myeloid lineage fate decisions and drug resistance.

    Evidence Retroviral overexpression in K562 and U937 cells with differentiation and clonogenicity readouts

    PMID:16094422

    Open questions at the time
    • Overexpression may not reflect endogenous function
    • Direct target genes not identified
  7. 2006 High

    Knockout mice established that LYL1 is genuinely required for HSC function and B-cell differentiation, moving it from candidate to essential regulator.

    Evidence Constitutive knockout with competitive reconstitution, progenitor frequency, and differentiation assays

    PMID:16514064 PMID:17053063

    Open questions at the time
    • Molecular targets mediating the HSC defect not yet defined
    • Redundancy with SCL not yet resolved
  8. 2007 Medium

    Defining LYL1 sequestration of E2A and a direct LYL1–CREB1 co-activation axis (recruiting p300/CBP) clarified two distinct transcriptional mechanisms—repression of E-protein activity and CREB-dependent gene activation.

    Evidence Mammalian two-hybrid, luciferase reporters, co-IP domain mapping, and ChIP-chip

    PMID:17486074 PMID:18160048

    Open questions at the time
    • In vivo relevance of CREB1 cooperation to hematopoiesis untested
    • Whether E2A sequestration drives transformation directly unresolved
  9. 2009 High

    Genetic epistasis demonstrated LYL1–SCL redundancy in adult HSC maintenance, with apoptosis as the cellular failure mode, resolving why single knockouts were partial.

    Evidence Conditional double-knockout mice with reconstitution, allelic dosage, and apoptosis analysis

    PMID:19200805

    Open questions at the time
    • Shared versus distinct target genes not fully mapped
    • Mechanism of redundancy at chromatin unaddressed
  10. 2009 Medium

    Physical LMO2–LYL1 interaction and reciprocal transcriptional induction connected LYL1 to the LMO2 regulatory module in leukemic cells.

    Evidence Co-IP, Western blot, RT-PCR, and transfection in K562 cells

    PMID:19671288

    Open questions at the time
    • Single lab with limited validation
    • Functional consequence of mutual induction not established
  11. 2010 Medium

    Identifying PEST-motif-driven proteasomal degradation defined how LYL1 protein abundance is controlled, independent of its MAPK phosphorylation.

    Evidence PEST deletion mutagenesis, proteasome inhibition, and phosphorylation assays in cells

    PMID:20844761

    Open questions at the time
    • E3 ligase mediating degradation not identified
    • Physiological signals regulating turnover unknown
  12. 2010 High

    Demonstrating an endothelial-intrinsic requirement for LYL1 in postnatal vessel maturation extended its role beyond hematopoiesis into vascular biology.

    Evidence Lyl1-deficient mice, hematopoietic reconstitution, tumor/Matrigel/aortic assays, and human EC knockdown

    PMID:20418284

    Open questions at the time
    • Direct transcriptional targets in endothelium not yet defined
    • Molecular link to junction stability not yet mechanistic
  13. 2012 High

    Identifying ANG-2 as a direct LYL1/TAL1/LMO2/GATA2 composite-element target, plus the lymphoid progenitor requirement via Gfi1 and CREB1 cooperation at STMN1, supplied concrete direct targets for LYL1 across vascular and lymphoid programs.

    Evidence ChIP, promoter mutagenesis, siRNA/shRNA knockdown, reporter assays, and knockout mouse lymphopoiesis analysis

    PMID:22404772 PMID:22772404 PMID:22792348 PMID:23000483

    Open questions at the time
    • Full target repertoire not genome-wide defined at this stage
    • Quantitative contribution of each target to phenotype unclear
  14. 2013 High

    Genetic epistasis showed LYL1, not SCL, is the obligate bHLH partner LMO2 must recruit to execute its oncogenic self-renewal program in T-ALL.

    Evidence Lmo2-transgenic mice crossed to Scl/Lyl1 knockouts, transplantation/replating, expression profiling, and knockdown in ETP-ALL lines

    PMID:23926305

    Open questions at the time
    • Chromatin targets of the leukemic LMO2-LYL1 complex not fully mapped
    • Basis for LYL1 versus SCL specificity unresolved
  15. 2014 High

    Defining the ARHGAP21/24–RhoA/Rap1–VE-cadherin axis provided the molecular mechanism by which LYL1 maintains endothelial barrier integrity.

    Evidence siRNA knockdown in human EC, Lyl1-deficient mouse lungs, permeability assays, junction immunofluorescence, and RhoA activity assays

    PMID:24532287

    Open questions at the time
    • Whether ARHGAP21/24 are direct transcriptional targets not established
    • Tissue-specificity of the axis beyond lung untested
  16. 2018 High

    Demonstrating LYL1–SCL redundancy in primitive erythropoiesis through GATA1 regulation extended the redundancy paradigm to embryonic blood formation.

    Evidence Conditional double-knockout mice with embryonic lethality endpoint and ChIP-seq in human erythroleukemia cells

    PMID:30185409

    Open questions at the time
    • LYL1 occupies only a small subset of SCL targets—basis for selectivity unclear
    • Mechanism of GATA1 regulation not detailed
  17. 2019 Medium

    Shared SCL/LYL1 function in megakaryopoiesis and a requirement downstream of NUP98-HOXD13 for thymocyte self-renewal broadened LYL1's roles in platelet biology and oncogenic self-renewal.

    Evidence Conditional Scl/Lyl1 double-knockout and NHD13-Tg/Lyl1-knockout mice with platelet function, transplantation, and ChIP-seq/transcriptome analyses

    PMID:30700838 PMID:31300405

    Open questions at the time
    • Direct versus indirect target relationships incompletely resolved
    • Mechanism linking LYL1 to self-renewal program not fully defined
  18. 2021 Medium

    Establishing a requirement for LYL1 in primitive macrophage and microglia development extended its lineage roles into yolk-sac myelopoiesis and neurodevelopment.

    Evidence bHLH-domain disruption knock-in mouse, transcriptomics of YS macrophage progenitors, flow cytometry, and in situ hybridization

    PMID:34887504

    Open questions at the time
    • Direct targets in primitive macrophages not identified
    • Single lab
  19. 2022 High

    Showing LYL1 nucleates AETFC complex assembly and recruits CARM1 at active enhancers defined a scaffolding/coactivator-recruitment mechanism for LYL1 in t(8;21) AML.

    Evidence Complex fractionation/co-IP, ChIP-seq, and CARM1 interaction assays

    PMID:36215477

    Open questions at the time
    • Whether scaffolding role generalizes to non-leukemic complexes untested
    • Structural basis of assembly not resolved
  20. 2024 Medium

    New contexts—an AR/BHLHE40-driven LYL1 senescence circuit in prostate cancer and a PU.1-downstream role in lymphoid commitment during EHT—indicate LYL1 functions beyond classical hematopoiesis.

    Evidence ChIP-seq, RNA-seq, co-IP, and knockdown/overexpression rescue in prostate cancer cells and human pluripotent stem cell differentiation

    PMID:39108738 PMID:39668349

    Open questions at the time
    • Generalizability of the senescence circuit beyond prostate cells unknown
    • Direct LYL1 targets in EHT lymphoid commitment not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The E3 ligase and upstream signals controlling LYL1 turnover, the structural basis for LYL1 versus SCL target selectivity, and a unified map of LYL1's direct genome-wide targets across each lineage remain unresolved.
  • No E3 ligase identified for PEST-dependent degradation
  • Basis of LYL1/SCL functional specificity at shared elements unknown
  • No structural model of LYL1-containing transcription complexes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3
Partners
BHLHE40CARM1CREB1GATA2LMO2NFKB1TAL1TCF3
Complex memberships
AETFC complex (AML1-ETO, CBFβ, HEB, E2A, LYL1, LMO2, LDB1)LMO2-GATA2-LYL1 complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 LYL1 encodes a protein containing a helix-loop-helix (HLH) DNA-binding motif, identified at the site of a t(7;19) chromosomal translocation breakpoint in T-cell ALL, where the gene is structurally altered and juxtaposed head-to-head with the T cell receptor Cβ gene, resulting in truncation of LYL1 RNA. Molecular cloning, chromosomal mapping, sequence analysis of translocation breakpoint Cell High 2752424
1991 Mouse Lyl-1 protein is 78% identical to human LYL1, with the highest similarity in the basic DNA-binding and HLH dimerization motifs (differing by only one conservative amino acid substitution). Expression is lineage- and differentiation-specific: present in B-lineage cells, downregulated during terminal differentiation, and absent in most T-lineage cells. cDNA cloning, Northern blot, sequence analysis, expression in lymphoid cell lines Oncogene High 2067848
1996 LYL1 forms heterodimeric complexes with E2A proteins (E12 and E47) via their HLH motifs. Endogenous LYL1-E2a complexes were detected in T-ALL and other cell lines by co-immunoprecipitation. The LYL1-E2a heterodimer binds a preferred DNA sequence 5'-AACAGATG(T/g)T-3', distinct from the muE2 site recognized by E2a homodimers. Yeast two-hybrid screen, in vitro interaction assay, co-immunoprecipitation of endogenous proteins, PCR-assisted site selection Molecular and cellular biology High 8628307
1999 LYL1 physically interacts with NF-κB1 p105 (precursor of p50). The interaction is mediated by the bHLH motif of LYL1 and the ankyrin-like motifs of p105, confirmed in vitro and by co-immunoprecipitation in mammalian cells. Ectopic LYL1 expression in a human T cell line caused significant decrease in NF-κB-dependent transcription and reduced NF-κB1 protein levels. Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation in mammalian cells, luciferase reporter assay Oncogene High 10023675
2003 The LYL1 promoter contains conserved binding sites for GATA-2 and Ets factors (Fli1, Elf1). These sites are occupied in vivo and drive expression in myeloid progenitor cells. Comparative genomic sequencing, transgenic reporter assays, chromatin immunoprecipitation (ChIP) Genomics Medium 12659809
2005 Forced overexpression of LYL1 in K562 cells enhanced erythroid differentiation and blocked megakaryocytic differentiation; in U937 cells it blocked monocytic differentiation and increased resistance to cytarabine, demonstrating LYL1 influences myeloid lineage fate decisions. Retroviral overexpression in cell lines (K562, U937), flow cytometry, clonogenicity assays Leukemia Medium 16094422
2006 Lyl-1 null mice show a reduced frequency of HSC (LSK, LSK-SP) populations in fetal liver and adult bone marrow, severely impaired competitive reconstituting ability (especially B and T lineage), and partial block in B-cell development after the pro-B stage, demonstrating that Lyl-1 is required for HSC function and B-cell differentiation. Knockout mouse model, flow cytometry, competitive bone marrow reconstitution assays, CFU-S12 and LTC-IC assays Blood High 16514064
2006 Lyl1 expression is controlled by GATA-2 and Ets factors (Fli1, Elf1, Erg, PU.1) binding to conserved sites in two closely spaced promoters, directing expression to hematopoietic progenitor, megakaryocytic, and endothelial cells. Despite coregulation with Scl by the same factors, Lyl1 (unlike Scl) cannot rescue hematopoietic differentiation in Scl−/− ES cells, indicating non-redundant early functions. Transgenic reporter mice, ChIP, ES cell differentiation rescue assay, comparative promoter analysis Blood High 17053063
2007 LYL1 overexpression in mice blocked E2A dimerization and inhibited E2A regulatory activity on the CD4 promoter (shown by mammalian two-hybrid and luciferase assay), with downregulation of E2A/HEB target gene expression, contributing to lymphomagenesis. Transgenic mouse model, mammalian two-hybrid, luciferase reporter assay, RT-PCR Oncogene Medium 17486074
2007 LYL1 interacts with CREB1 via LYL1's N-terminal domain and CREB1's Q2 and KID domains. Histone acetyltransferases p300 and CBP are recruited to LYL1-CREB1 complexes independently of CREB1 Ser133 phosphorylation. The LYL1-CREB1 complex activates the Id1 promoter and other CREB1 target promoters (Id3, cyclin D3, Brca1, Btg2, Egr1). ChIP-chip showed ~50% of LYL1-occupied promoters are co-occupied by CREB1. Co-immunoprecipitation, luciferase reporter assay, ChIP-chip, domain-mapping experiments Biochimica et biophysica acta Medium 18160048
2009 Lyl1 and Scl show genetic redundancy in adult HSC maintenance: Lyl1;Scl conditional double-knockout mice show rapid loss of hematopoietic progenitors due to apoptosis, and a single allele of Lyl1 (but not Scl) rescues HSC function in this background. Conditional double-knockout mice, bone marrow reconstitution assays, flow cytometry, apoptosis analysis Cell stem cell High 19200805
2009 Multiple mechanisms activate ectopic LYL1 expression in T-ALL cell lines: microdeletions upstream of LYL1 (targeting TRMT1) and amplification; transcription factors HOXA10, LMO2, and NKX2-5 bind and activate the LYL1 promoter as shown by overexpression, reporter gene assays, and ChIP. Quantitative genomic PCR, sequence analysis, reporter gene assay, chromatin immunoprecipitation, expression profiling Leukemia research Medium 19608273
2010 LYL1 is degraded by the proteasome via an N-terminal PEST sequence motif. Deletion of the PEST site leads to LYL1 accumulation. LYL1 is phosphorylated by MAPK at Ser36, but proteasomal degradation proceeds in a phosphorylation-independent manner. Cell-based degradation assays, PEST motif deletion mutagenesis, proteasome inhibitor treatment, MAPK phosphorylation assay PloS one Medium 20844761
2010 LYL1 is required for postnatal maturation of newly formed blood vessels. Lyl1-deficient mice show enlarged tumor vessel lumens, reduced pericyte coverage, increased permeability, and upregulation of Tal-1, VE-Cadherin target genes, and Angiopoietin-2. This phenotype is of endothelial origin (shown by hematopoietic reconstitution). LYL1 depletion in human endothelial cells reduces expression of molecules involved in vascular stabilization. Lyl1-deficient mouse model, hematopoietic reconstitution experiments, tumor implantation assay, Matrigel plug assay, aortic explant assay, siRNA knockdown in human endothelial cells Blood High 20418284
2012 ANGIOPOIETIN-2 (ANG-2) is a direct transcriptional target of LYL1, TAL1, and LMO2 in endothelial cells. ChIP assays show LYL1, TAL1, LMO2, and GATA2 occupy a conserved Ebox-GATA composite element in the ANG-2 promoter. LMO2 assembles LYL1-LYL1 or LYL1-TAL1 dimers with GATA2 into a complex capable of activating endogenous ANG-2 expression. Chromatin immunoprecipitation, siRNA knockdown, transient transfection/promoter reporter assay, RT-PCR and protein detection PloS one High 22792348
2012 Lyl-1 deficiency results in profound defects in generation of lymphoid-primed multipotent progenitors (LMPPs), common lymphoid progenitors (CLPs), and early T lineage progenitors (ETPs), with increased apoptosis and blocked differentiation. Gfi1 was identified as a critical transcriptional target of Lyl-1 in T lymphopoiesis. Lyl1 knockout mouse, flow cytometry, apoptosis assay, gene expression analysis identifying Gfi1 as target Nature immunology High 22404772 22772404
2012 LYL1 and CREB1 co-occupy the STMN1 (stathmin/Op18) promoter in vivo and cooperatively activate STMN1 transcription. NLI, LMO2, and GATA2 potentiate Lyl1 activation of STMN1. Mutations of CRE sites or CREB1 DNA-binding domain abolish LYL1 transactivation. TAL1 (close LYL1 paralog) had no effect on the STMN1 promoter. ChIP-chip, promoter reporter assay with site-directed mutagenesis, shRNA knockdown Biochimica et biophysica acta Medium 23000483
2013 Lyl1 (but not Scl) is required for all oncogenic functions of Lmo2 in T-ALL, including upregulation of a stem cell-like gene signature, aberrant self-renewal of thymocytes, and generation of T-cell leukemia in Lmo2-transgenic mice. LMO2 must recruit Lyl1 to DNA to exert these effects. Lyl1 expression is restricted to preleukemic and leukemic stem cell populations. Lmo2-transgenic mice crossed with Scl- or Lyl1-knockout mice, transplantation/serial replating assays, gene expression profiling, LYL1 knockdown in ETP-ALL cell lines Blood High 23926305
2014 LYL1 is required for pulmonary endothelial barrier integrity. LYL1 knockdown in human endothelial cells downregulates ARHGAP21 and ARHGAP24 (Rho GTPase-activating proteins), leading to increased RhoA activity and actin cytoskeleton reorganization into stress fibers. In Lyl1-deficient mouse lungs, VE-cadherin and p120-catenin are poorly recruited to adherens junctions, and lung vascular permeability is constitutively elevated. LYL1 acts upstream of VE-cadherin and the GTPases Rap1 and RhoA. siRNA knockdown in human endothelial cells, Lyl1-deficient mice, Evans blue permeability assay, immunofluorescence for junction proteins, RhoA activity assay American journal of physiology. Lung cellular and molecular physiology High 24532287
2018 Lyl1 can maintain primitive erythropoiesis redundantly with Scl. DKO (reduced Scl + absent Lyl1) embryos die at E10.5 due to progressive loss of erythropoiesis, with loss of Gata1 and known SCL-GATA1 target genes. ChIP-seq in human erythroleukemia cells showed LYL1 exclusively bound a small subset of SCL targets including GATA1. Conditional double-knockout mice, embryonic viability assay, gene expression profiling, ChIP-seq Development (Cambridge, England) High 30185409
2019 Lyl1 and Scl share functional roles in megakaryopoiesis and platelet production. Pf4Sclc-KO/Lyl1-null double-knockout mice have severe macrothrombocytopenia, abnormal megakaryocyte morphology, defective proplatelet formation, and impaired platelet aggregation. DKO megakaryocytes had reduced expression of Gata1, Fli1, Nfe2, and other thrombocytopenia genes. Shared Scl/Lyl1 E-box binding sites were enriched for Gata1, Ets, and Runx1 motifs. Conditional Scl/Lyl1 double-knockout mice, platelet function assays, gene expression profiling, ChIP-seq binding site analysis Blood High 31300405
2019 NUP98-HOXD13 induces thymocyte self-renewal via a Lmo2/Lyl1-dependent stem cell-like transcriptional program. Lyl1 is essential for expression of this self-renewal gene program; NHD13-Tg/Lyl1-knockout mice showed accelerated T-ALL and loss of self-renewal, demonstrating Lyl1 is required downstream of the NUP98-HOXD13 oncogene for thymocyte self-renewal. Transgenic/knockout mice, serial transplantation, transcriptome analysis Leukemia Medium 30700838
2009 LMO2 and LYL1 physically interact (LMO2-LYL1 complex detected by co-IP) in myeloid leukemia cells. Transfection of LMO2 upregulates LYL1 expression and vice versa, indicating mutual transcriptional stimulation. Co-immunoprecipitation, Western blotting, RT-PCR, transfection in K562 cells Zhonghua yi xue za zhi Medium 19671288
2022 LYL1 is required for assembly of the larger AETFC complex (containing AML1-ETO, CBFβ, HEB, E2A, LYL1, LMO2, and LDB1) in t(8;21) AML. LYL1-containing AETFC preferentially binds active enhancers and promotes AE-dependent gene activation. LYL1 recruits the coactivator CARM1 to AETFC at chromatin to facilitate gene activation. Biochemical co-immunoprecipitation/complex fractionation, ChIP-seq, genomic approaches, CARM1 interaction assays Proceedings of the National Academy of Sciences of the United States of America High 36215477
2021 Lyl-1 is required for primitive macrophage and microglia development. Lyl-1 is expressed in yolk sac primitive macrophage progenitors. Disruption of the bHLH domain of Lyl-1 leads to increased emergence of primitive macrophage progenitors followed by defective differentiation, with disrupted expression of gene sets related to embryonic patterning and neurodevelopment, and reduced mature macrophages/microglia in the early brain. Lyl-1 bHLH domain disruption (knock-in model), transcriptomic analysis of YS macrophage progenitors, flow cytometry, in situ hybridization Communications biology Medium 34887504
2024 LYL1 is upregulated by BHLHE40 (a clock gene) in response to supraphysiological androgen in prostate cancer cells. AR and BHLHE40 are directly recruited to the LYL1 gene locus (ChIP-seq). LYL1 forms a complex with BHLHE40 and AR (co-immunoprecipitation). LYL1 mediates SAL-induced cellular senescence; its knockdown enhances BHLHE40 expression via a negative feedback loop involving p27kip1. Loss of LYL1 promotes rather than suppresses senescence in this context. ChIP-seq, RNA-seq, co-immunoprecipitation, siRNA knockdown, qRT-PCR, immune detection Cell communication and signaling : CCS Medium 39668349
2024 LYL1 acts downstream of SPI1 (PU.1) in regulating lymphoid lineage commitment during endothelial-to-hematopoietic transition (EHT). Overexpression of LYL1 partially rescues the SPI1 knockdown-induced reduction in hematopoietic progenitor formation, specifically restoring lymphoid lineage potential. SPI1 knockdown, LYL1 overexpression rescue, multi-omic analysis, hematopoietic differentiation assays from human pluripotent stem cells iScience Medium 39108738

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 lyl-1, a novel gene altered by chromosomal translocation in T cell leukemia, codes for a protein with a helix-loop-helix DNA binding motif. Cell 343 2752424
1993 TAL1, TAL2 and LYL1: a family of basic helix-loop-helix proteins implicated in T cell acute leukaemia. Seminars in cancer biology 117 8142619
2009 Adult hematopoietic stem and progenitor cells require either Lyl1 or Scl for survival. Cell stem cell 111 19200805
2006 The SCL relative LYL-1 is required for fetal and adult hematopoietic stem cell function and B-cell differentiation. Blood 70 16514064
2006 The paralogous hematopoietic regulators Lyl1 and Scl are coregulated by Ets and GATA factors, but Lyl1 cannot rescue the early Scl-/- phenotype. Blood 67 17053063
2013 Requirement for Lyl1 in a model of Lmo2-driven early T-cell precursor ALL. Blood 60 23926305
2012 The transcription factor Lyl-1 regulates lymphoid specification and the maintenance of early T lineage progenitors. Nature immunology 52 22772404
1996 Helix-loop-helix proteins LYL1 and E2a form heterodimeric complexes with distinctive DNA-binding properties in hematolymphoid cells. Molecular and cellular biology 50 8628307
1991 Structure, chromosome mapping, and expression of the mouse Lyl-1 gene. Oncogene 48 2067848
2007 Overexpression of a transcription factor LYL1 induces T- and B-cell lymphoma in mice. Oncogene 37 17486074
1999 Physical interaction of the bHLH LYL1 protein and NF-kappaB1 p105. Oncogene 33 10023675
2005 Oncogenic potential of the transcription factor LYL1 in acute myeloblastic leukemia. Leukemia 31 16094422
2003 Comparative and functional analyses of LYL1 loci establish marsupial sequences as a model for phylogenetic footprinting. Genomics 31 12659809
2011 Characterization of a pediatric T-cell acute lymphoblastic leukemia patient with simultaneous LYL1 and LMO2 rearrangements. Haematologica 29 22058201
2009 Multiple mechanisms induce ectopic expression of LYL1 in subsets of T-ALL cell lines. Leukemia research 25 19608273
2006 lyl-1 and tal-1/scl, two genes encoding closely related bHLH transcription factors, display highly overlapping expression patterns during cardiovascular and hematopoietic ontogeny. Gene expression patterns : GEP 25 17112790
2007 Lyl1 interacts with CREB1 and alters expression of CREB1 target genes. Biochimica et biophysica acta 23 18160048
2012 Angiopoietin-2 is a direct transcriptional target of TAL1, LYL1 and LMO2 in endothelial cells. PloS one 22 22792348
2022 Super-enhancer profiling identifies novel critical and targetable cancer survival gene LYL1 in pediatric acute myeloid leukemia. Journal of experimental & clinical cancer research : CR 21 35842703
2022 BRD4 Inhibitor GNE-987 Exerts Anticancer Effects by Targeting Super-Enhancer-Related Gene LYL1 in Acute Myeloid Leukemia. Journal of immunology research 16 35958877
2011 LYL-1 deficiency induces a stress erythropoiesis. Experimental hematology 15 21420467
2010 LYL1 activity is required for the maturation of newly formed blood vessels in adulthood. Blood 15 20418284
2014 Lung endothelial barrier disruption in Lyl1-deficient mice. American journal of physiology. Lung cellular and molecular physiology 14 24532287
2019 The NUP98-HOXD13 fusion oncogene induces thymocyte self-renewal via Lmo2/Lyl1. Leukemia 12 30700838
2019 Shared roles for Scl and Lyl1 in murine platelet production and function. Blood 12 31300405
2022 LYL1 facilitates AETFC assembly and gene activation by recruiting CARM1 in t(8;21) AML. Proceedings of the National Academy of Sciences of the United States of America 11 36215477
2021 Lyl-1 regulates primitive macrophages and microglia development. Communications biology 10 34887504
2018 A novel role for Lyl1 in primitive erythropoiesis. Development (Cambridge, England) 10 30185409
2024 SPI1-KLF1/LYL1 axis regulates lineage commitment during endothelial-to-hematopoietic transition from human pluripotent stem cells. iScience 7 39108738
2011 A new allele of Lyl1 confirms its important role in hematopoietic stem cell function. Genesis (New York, N.Y. : 2000) 7 21387538
2010 LYL1 degradation by the proteasome is directed by a N-terminal PEST rich site in a phosphorylation-independent manner. PloS one 7 20844761
2012 Suspected leukemia oncoproteins CREB1 and LYL1 regulate Op18/STMN1 expression. Biochimica et biophysica acta 6 23000483
2010 The expansion of T-cells and hematopoietic progenitors as a result of overexpression of the lymphoblastic leukemia gene, Lyl1 can support leukemia formation. Leukemia research 6 20705338
2024 Functional circuits of LYL1 controlled by supraphysiological androgen in prostate cancer cells to regulate cell senescence. Cell communication and signaling : CCS 4 39668349
2020 In Lyl1-/- mice, adipose stem cell vascular niche impairment leads to premature development of fat tissues. Stem cells (Dayton, Ohio) 3 33022858
2022 Lyl1-deficiency promotes inflammatory responses and increases mycobacterial burden in response to Mycobacterium tuberculosis infection in mice. Frontiers in immunology 1 36119114
2009 [Abnormal expression of transcription factors LYL1 and LMO2 and interaction between them in myeloid leukemia]. Zhonghua yi xue za zhi 1 19671288
2008 [Expression of transcription factor LYL1 in leukemia and its possible role in leukemogenesis]. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 1 19176012
2026 LYL1 is critical for adult hematopoietic stem cell-derived B and T lymphopoiesis. Scientific reports 0 42174007
2025 Role of different Lyl1 transcripts in zebrafish primitive hematopoiesis. Yi chuan = Hereditas 0 40287790
2024 Multiple primary tumors in a patient with non‑small‑cell lung cancer harboring mutations in ERCC6 and LYL1: A case report. Oncology letters 0 39611066

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