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FLASH GENE
Symbol TCF4 contributors: mct/shn - updated : 31-01-2016
HGNC name transcription factor 4
HGNC id 11634
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)