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Symbol LEF1 contributors: mct - updated : 29-04-2020
HGNC name lymphoid enhancer-binding factor 1
HGNC id 6551
Location 4q25      Physical location : 108.968.700 - 109.090.112
Synonym name T cell factor 1 alpha
Synonym symbol(s) TCF1A, TCF1ALPHA, DKFZp586H0919, LEF-1, FLJ46390, TCF10, TCF7L3
TYPE functioning gene
STRUCTURE 121.41 kb     12 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site
text structure
  • bound to four sites in the LEF1 promoter, either directly or indirectly through TCF complexes
  • context-dependent binding sites in the promoter that facilitate protein-protein interactions between SOX17 and TCF4
  • two promoters: the P1 promoter drives the expression of a full-length LEF1 polypeptide; the P2 promoter instead produces a truncated protein that lacks the beta-catenin binding domain and supresses WNT signalling
  • MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    text several transcripts generated by alternative splicing and expressed in lymphocytes by a specific promoter
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 splicing 3620 44.2 399 - 2011 21444716
  • inclusion of exon 6 is dependent on the signal-induced increase in expression and binding of the splicing factor CELF2 to two intronic sequences flanking the regulated exon
  • inclusion of LEF1 exon 6 is increased during thymic development and in response to signaling in a cultured T-cell line in a manner which temporally correlates with increased expression of TCR-alpha
  • 11 splicing 3536 - 371 - 2000 10756202
  • lacking HMG domain due to alternative splicing of exon 8
  • truncated protein
  • 10 splicing 3495 - 386 - 2000 10756202
    11 splicing 2660 - 303 - 2000 10756202
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Hearing/Equilibriumear   highly
    Lymphoid/Immunethymus   highly
    Nervousbrainlimbic systemhippocampusdentate gyrus  Homo sapiens
    Reproductivemale systemtestis  highly
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneT cell
    Nervousneuron Homo sapiens
    cell lineage preB cells
    cell lines
    at STAGE
    physiological period fetal
    Text cochlea, in embryonic skin, expressed in basal progenitors
  • a N terminal beta-catenin domain,
  • a context-dependent transactivation domain and
  • an high mobility group (HMG) domain
  • proline-rich and acidic regions implicated in the activation functions of RNA polymerase II transcription factors
  • conjugated Other
    interspecies ortholog to murine Lef1
    intraspecies homolog to HMG1
  • LEF1/T-cell-factor (TCF) family of transcription factors
  • high mobility group (HMG) family of proteins
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • catalyzing the crucial step of the production of prostaglandin E2, which is a principal mediator of joint inflammation such as rheumatoid arthritis and osteoarthritis
  • confering maximal enhancer activity to the T-cell receptor-alpha enhancer
  • mediating the proliferation, survival and differentiation of granulocyte progenitor cells
  • regulating expression of cytokeratin genes involved in formation of hair follicles and the gene encoding the cell-adhesion molecule E-cadherin
  • instructive factor regulating neutrophilic granulopoiesis whose absence plays a critical role in the defective maturation program of myeloid progenitors in congenital neutropenia
  • plays important roles in organogenesis and colon cancer progression
  • having a role as a mediator of IL1B signaling in inflammatory process and constitutes further evidence for the role of WNT/CTNNB signaling in cartilage degeneration
  • directly regulating PTGS2 expression with CTNN1B in arthritic chondrocytes
  • having negative regulatory role in mature peripheral T cells and negatively controls interleukin-4 expression through a proximal promoter regulatory element
  • playing a role in the biology of acute leukemia, pointing to the necessity of balanced LEF1 expression for an ordered hematopoietic development
  • role in the Wnt signaling cross-talk that contributes to the initiation steps in hair follicle morphogenesis
  • high-mobility group of transcriptional factors that play essential roles in cell fate determination during early embryogenesis and ontogenesis
  • controls many developmentally regulated genes, including genes that activate expression of the T-cell antigen receptor alpha chain (TCR-alpha) in developing thymocytes
  • is a critical mediator of ERG-induced tumorigenesis
  • is an important factor for hematopoietic stem cells (HSCs) and progenitor function and that its stem cell regulatory role depends on its DNA binding ability
  • LEF1 promoted proliferation of renal cell carcinoma (RCC) cells depending on suppressing G2/M cell-cycle arrest
  • essential role for TCF7 and LEF1 in development of NKT cells
  • LEF1 reduces tumor progression and induces myodifferentiation in a subset of rhabdomyosarcoma
  • regulates circuit development that is fundamentally important for mediating anxiety in a wide variety of animal species
  • is required for neurogenesis
  • overexpressing LEF1 is sufficient to enhance neurogenesis, uncovering a novel mechanistic link between the BMP/WNT signalling pathways operating in adult hippocampal neural stem and progenitor cells
  • promotes stemness and poor differentiation of hepatocellular carcinoma by directly activating the NOTCH pathway
  • CELLULAR PROCESS nucleotide, transcription, regulation
    a component
  • binding the armadillo repeat of CTNNB1
  • interaction with EP300, TLE1 and PIASG
    DNA binding to a functionally important site in the T-cell receptor-alpha enhancer
    small molecule
  • binding to TCF4 and beta catenin for activation of wingless (WNT) responsive genes
  • TGFB, WNT, MADH4 for controlling critical developmental processes
  • interaction with MITF
  • with CTNNB (LEF1-interacting protein)
  • interaction partner of PIAS4 (coexpression with LEF1 results in potent repression of LEF1 activity and in covalent modification of LEF1 with SUMO)
  • interacting with VENTX (might act as a potential tumor suppressor by controlling LEF1-mediated transcription)
  • interaction between VDR and LEF1 that is mediated by the DNA-binding domain of the VDR and that is required for normal canonical Wnt signaling in keratinocytes
  • HMGB2 regulates MSC (mesenchymal stem cell) chondrogenesis in part by modulating the LEF1-dependent transactivation of RUNX2
  • LEF1 mediated looping between promoter and 3prime UTR under the permissive chromatin architecture upregulates COL2A1 expression in primary chondrocytes
  • LEF1 acts as a switch activating DSC2 and repressing DSC3 in the presence of JUP
  • LEF1 can act as a switch between DSC2 and DSC3 expression and the presence of LEF1 in keratinocytes can suppress the DSC3 gene
  • LEF1 is a direct target of ERG and LEF1 inhibition fully abolished ERG-induced WNT signaling and target gene expression
  • CTNND1 interacts with LEF1 and negatively regulates its transcriptional activity
  • LEF1 overexpression increased TYR gene promoter activity, whereas LEF1 knockdown by RNA interference significantly decreased TYR expression
  • SOX2 and LEF1 interact with PITX2 to regulate incisor development and stem cell renewal
  • interaction between LEF1 and WWTR1 is crucial for the osteoblastogenic activity of WNT3A and LEF1 and WWTR1 contribute to the cooperative effect of WNT3A and BMP2 on osteoblast differentiation through association with RUNX2
  • interplay of WNT1-LEF1 and TGFB1-SMAD3 signaling activates canonical WNT1 target promoters in a manner that depends on CTNNB1 during myoblast proliferation but is independent of CTNNB1 during Skeletal muscle stem cells (MuSCs) quiescence
  • LEF1 could activate the critical members (NOTCH1 and NOTCH2) of the NOTCH signaling pathway through directly binding to their promoter regions
  • cell & other
    inhibited by TGFB1I1
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral germinal mutation     loss of function
    inactivating mutationsin sebaceous tumors
    constitutional     --low  
    in congenital neutropenia
    constitutional     --over  
    in the cartilage tissue of osteoarthritic patients
    tumoral   deletion    
    in acute lymphoblastic leukaemia
    tumoral     --over  
    in androgen-independent prostate cancer, potentially serving as a marker for androgen-independent disease
    tumoral     --over  
    high LEF1 expression identifies B-precursor ALL patients with inferior relapse-free survival (RFS, supporting a pathogenetic role of Wnt signaling in ALL
    tumoral     --over  
    associated with aberrant clinicopathological characteristics and the poor prognosis of Esophageal squamous cell carcinoma (ESCC) patients
    Variant & Polymorphism
    Candidate gene potential marker for androgen-independent disease and as a key regulator of AR expression and prostate cancer growth and invasion
  • positive expression of LEF1 protein may act as valuable independent biomarker to predict poor prognosis for patients with nasopharyngeal carcinoma (NPC)
  • LEF1 is a sensitive and specific marker for chronic lymphocytic B-cell leukemia (CLL) and is helpful in the diagnosis of diagnostically challenging small B-cell lymphomas
  • Therapy target
    inhibition of LEF1 might therefore be a novel therapeutic target to inactivate cancer stem cells (CSCs) and inhibit tumor progression
    TCF7 and LEF1 transcription factors are novel therapeutic targets in treating hematological malignancies
    might serve as a therapeutic target in treating advanced renal cell carcinoma (RCC)