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FLASH GENE
Symbol TCF4 contributors: mct/shn - updated : 31-01-2016
HGNC name transcription factor 4
HGNC id 11634
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Digestivepharynx   highly
Nervousbrain   highly Homo sapiens
Respiratorylung    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow  highly
Connectiveadipose  highly
Connectivebone   
Muscularstriatumskeletal  
cell lineage preB cells
cell lines neuroblastoma cells (
fluid/secretion blood
at STAGE
physiological period embryo, pregnancy
Text heart, brain, placenta
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a basic helix-loop-helix (HLH) DNA binding domain
  • two binding domains for C terminal binding protein
  • both TCF4 activation domains are able to activate transcription independently, but act synergistically in combination
  • C-terminal bHLH domain that mediates dimerization and DNA binding, and the transcriptional activation domain 2
  • mono polymer homomer , heteromer , dimer , trimer
    HOMOLOGY
    interspecies ortholog to Tcf4, Rattus Norvegicus
    ortholog to Tcf4, mus musculus
    ortholog to tcf4, Danio rerio
    Homologene
    FAMILY
  • basic helix-loop-helix (BHLH) family of transcription factors
  • CATEGORY transcription factor , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • playing a role in regulation of melanogenesis through melanocyte differentation and regulation of melanogenic genes
  • regulating intestinal tumorigenesis by interaction with c-Jun (by integrating JNK and APC/beta-catenin, two distinct pathways activated by WNT signaling)
  • playing an important role in neural development and differentiation
  • playing a prominent role in the regulation of differentiation processes
  • key transcription factor, with TCF3, that collaborate with beta-catenin in its established role in hair follicle stem cell activation
  • with TCF3 may be essential for establishing and maintaining all skin epithelial stem cells through Wnt-dependent and Wnt-independent roles
  • regulates a number of convergent signaling pathways involved in cell differentiation and survival in addition to a subset of clinically important mental retardation genes
  • a dynamic interplay of TCF3,TCF4 transcription factors governs MYC gene expression in colo-rectal cancer
  • TCF3 together with TCF4 controlled germinal center (GC) B cell and plasma cell development
  • TCF3, TCF4 are central regulators of B cell immunity
  • CELLULAR PROCESS cell life, differentiation
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    text transcriptional activator
    PATHWAY
    metabolism
    signaling signal transduction
    Wnt signaling pathway
    a component
  • forming homodimers or heterodimers with myogenin
  • forming a ternary complex with JUN, CTNNB1 (beta-cetanin)
  • heterodimerize with several bHLH transcription factors that play important roles in the development of the nervous system, ATOH1, ASCL1, NEUROD1 and NEUROD2
  • INTERACTION
    DNA
  • binding to the E box in the promoter SSTR2 (
  • preferentially binding to either 5'- ACANNTGT-3' or 5'-CCANNTGG-3'
  • RNA
    small molecule
    protein
  • myogenic differentiation 1, MyoD1 (
  • Id1, Id2, and Id3 (
  • fibroblast growth factor (FGF)-1 promoter, FGF-1.B (
  • calmodulin (
  • HASH1 (
  • Id4 (
  • beta-catenin, CTNNB (
  • Math1 (
  • menin (
  • CDX2
  • FGFR3
  • ZEB1 is an effector of CTNNB1/TCF4 signaling in epithelial-to-mesenchymal transition and tumor progression
  • FAM96B is an interaction partner of TCF4
  • binds to E-box DNA sequences (CANNTG)
  • SOX9 regulates LRP6, TCF4 expression and WNT/CTNNB1 activation in breast cancer
  • AGBL1 interacts biochemically with the FCD (Fuchs corneal dystrophy) -associated protein TCF4 and the mutations found in our cohort of FCD individuals diminish this interaction
  • PLAGL1 interacts with TCF4, and PLAGL1 and TCF4 expression concomitantly increased during neuronal progenitor differentiation
  • WNT1 regulates the expression of CD36 through TCF4 and PPARG
  • suppresses angiogenesis after ischemic injury and impairs Wnt/CTNNB1 signaling by disrupting the interaction between CTNNB1 and TCF4
  • SPINDOC associates with TCF4 in a SPIN1-dependent manner and dampens SPIN1 coactivator activity
  • ZNF433 enhanced the binding between CTNNB1 and TCF4
  • KIFC1, activated by TCF4, functions as an oncogene and promotes HCC pathogenesis through regulating HMGA1 transcriptional activity
  • cell & other
  • Ephrussi box-like motif within the glucocorticoid response element in the enhancer of the murine leukemia virus SL3-3 (
  • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) PTHS , DEL18QD , FECD3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional        
    bipolar disorder
    Susceptibility
  • to schizophrenia
  • to autism
  • to Fuchs' corneal dystrophy (
  • Variant & Polymorphism SNP , repeat
  • very enlarged CTG alleles maybe associated to bipolar disorder
  • a marker in intron 4 specifically associated to schizophrenia
  • region of hemizygosity including TCF4, NETO1, and FBXO15 significantly more likely to exhibit autistic-like behaviors
  • rs17089887 and rs17089925 strongly associated with Fuchs' corneal dystrophy (
  • association of TCF4 (rs613872, rs9954153, rs2286812 )wih Fuchs' corneal dystrophy
  • Candidate gene for severe mental retardation in del18q
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurosensorialvisualanterior chamber
    targeted (CAG)7 ASO (antisense oligonucleotide) treatment reduces gain-of-function RNA toxicity induced by TCF4 CTG18.1 expansion, in a cellular and human genomic context
    ANIMAL & CELL MODELS
  • Tcf4(-/-) mice have disrupted pontine nucleus development (
  • Tcf3/4-null primary mouse keratinocyte cultures show a growth defect, with inability to maintain long-term epidermal homeostasis (Nguyen 2009)