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Symbol TWIST1 contributors: mct/pgu - updated : 21-08-2016
HGNC name twist homolog 1 (Drosophila)
HGNC id 12428
Type restricted
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Respiratoryrespiratory tractlarynx   
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadipose  highly
Muscularstriatumskeletal   Homo sapiens
SystemCellPubmedSpeciesStageRna symbol
not specificadipocyte
cell lineage
cell lines
physiological period embryo, fetal, pregnancy
Text placenta, head and limb buds, skin, mesodermal and neural crest cells
  • a basic DNA binding structure
  • two putative NLS motifs and these NLS sequences are potentially functional
  • a C terminal basic helix-loop-helix (HLH) domain with a stretch of glycine, GGC repeat, and anti-osteogenic C-terminus, the TWIST Box, which binds and inhibits RUNX2 transactivation, and through its Twist-box, binds directly to the SOX9 HMG DNA-binding domain, leading to inhibition of SOX9-dependent gene activation
  • mono polymer homomer , heteromer , dimer
    interspecies homolog to murine Dermo1
    intraspecies homolog to TAL2
  • BHLH family of transcription factors
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • involved in osteoblast differentiation and maturation
  • interacting with the histone acetyltransferase domain of PCAF and EP300 and inhibiting their acetyltransferase
  • activities
  • regulator of embryonic morphogenesis and playing an essential role in metastasis by promoting an epithelial-mesenchymal transition
  • required for the dorsoventral patterning and for maintenance of the overlying apical ectodermal ridge
  • promotes survival and accumulation of fibroblasts by shaping their responsiveness to growth factor stimulation, and can promote pathogenic accumulation of fibroblasts in fibrotic lung disease
  • mediators of mesodermal tissue development and contribute to correct patterning of the skeleton
  • potential mediator of mesenchymal stromal/stem cells self-renewal and lineage commitment in postnatal skeletal tissues by exerting their effects on genes involved in the early stages of bone development
  • regulator of epithelial-mesenchymal transition(EMT)in lung fibrosis
  • may play a role in inflammation of white adipose tissue because it can regulate the expression and secretion of inflammatory adipokines via direct transcriptional effects in white adipocytes
  • may be a positive regulator of fatty acid oxidation in human white adipocytes
  • TWIST1 and BMI1 act cooperatively to repress expression of both E-cadherin and CDKN2A
  • directly activates BMI1 transcription by binding to the E-box in intron 1 of the BMI1 gene
  • TWIST1 and BMI1 are mutually essential to induce EMT and promote tumour-initiating capability in cancer cells
  • TWIST1 and SNAI2 act together to promote epithelial mesenchymal transition and tumor metastasis
  • master osteogenic regulator, and regulator in giant cell tumor of bone
  • TWIST1 and TWIST2 regulate osteocalcin transcription in part through the interaction of the C-terminal "box" domain in these factors and RUNX2
  • suppresses cartilage development by directly inhibiting the transcriptional activity of SOX9, the master regulator of chondrogenesis
  • transcription factor that is involved in epithelial–mesenchymal transition by suppressing intercellular adhesion
  • induces the repression of CLDN4 expression during the epithelial–mesenchymal transition in esophageal carcinoma
  • functions in post-migratory neural crest cells to repress pro-neural factors and thereby regulate cell fate determination between ectodermal and mesodermal lineages
  • TWIST1 reverses muscle cell differentiation through binding and down-regulation of myogenin (MYOG)
  • induced dramatic transcriptional changes in extracellular compartment and cell-matrix adhesion genes but not in cell-cell adhesion genes
  • is a key downstream effector of SQSTM1 in regulation of cell proliferation and migration
  • promotes epithelial-to-mesenchymal transition (EMT), invasion, metastasis, and cancer stem cell (CSC) properties
  • is required for skin tumor initiation and progression in a gene-dosage-dependent manner
  • TWIST1 and TWIST2 regulate glycogen storage and inflammatory genes in skeletal muscle
  • vital association is exist between the epithelial mesenchymal transition (EMT) and the acquisition of cancer stemness state in tumor cells through the TWIST1/CTAG1B axis and it can be a critical hallmark in esophageal squamous cell carcinoma (ESCC) tumorigenesis
  • CELLULAR PROCESS cell life, antiapoptosis
    nucleotide, transcription
    text antiapoptotic role in calvarial osteoblasts
    a component
  • heterodimerizing with E12 protein
  • heterodimering with partner BHLH proteins and with HAND2 (coexpressed in distinct regions of the developing limb)
  • linked with SNAIL and TCF3 during embryonic development
  • dosage of TCF12-TWIST1 heterodimers is critical for normal coronal suture development
    small molecule
  • interacting with RUNX1 in osteoblasts
  • binding to FGFR2 promoter and interacting with RUNX2
  • overexpression of WDR5 in the perichondrium promotes chondrocyte differentiation by modulating the expression of TWIST1 and FGF18
  • regulating with MSX2 the expression of EFNA4
  • interaction of TWIST1 with a novel protein candidate TCF4
  • direct regulation of BMI1 by TWIST1, and the functional interdependence between TWIST1 and BMI1, involved in promoting EMT and the tumour-initiating capability of head and neck cancer cells
  • SNAI1 controls ZEB1 expression at multiple levels and acts cooperatively with TWIST1 in the ZEB1 gene transcription induction
  • TWIST1, TWIST2 are novel inhibitory binding partners of ATF4
  • SETD8 acts as a dual epigenetic modifier on the promoters of the TWIST1 target genes CDH1 and CDH2 via its H4K20 monomethylation activity
  • TWIST1 binds directly to SOX9 and inhibits both SOX9-dependent gene activation and SOX9 binding to target gene enhancer DNA in chondrogenic cells
  • is an inhibitor of SOX9, suggesting that the balance between TWIST1 and SOX9 may determine the earliest steps of chondrogenesis
  • up-regulation of TWIST1 decreased both gene and protein expression levels of endogenous CLDN4 and the suppression was mediated by direct binding of TWIST1 to the canonical E-box in the promoter region of CLDN4
  • TWIST1 regulation of IFNG depends on complex formation with RUNX3
  • regulatory cascade containing PPARG and TWIST1 that controlled the expression of GPS2 and NCOR2 in human adipocytes
  • TWIST1 expression did not increase the secretion of the common proangiogenic factors VEGFA and basic fibroblast growth factor but rather induced expression of the macrophage chemoattractant CCL2
  • interacts with the pro-neural factor SOX10 via its Twist-box domain and binds to the PHOX2B promoter to repress transcriptional activity
  • is an important potential downstream effector, playing a key role in TFF3-modulated metastasis in gastric cancer
  • HDAC5 promotes osteosarcoma progression by upregulation of TWIST1 expression
  • SOX5 transactivates TWIST1 expression and plays an important role in the regulation of breast cancer progression
  • SQSTM1 binds to TWIST1 and inhibits degradation of TWIST1
  • TWIST1-binding sequences associated with CHST11, LITAF, ROR2, and SPATA5 also bound the potential TWIST1 cofactor RREB1
  • is required for tumor initiation and maintenance in a TP53-dependent and -independent manner
  • NOTCH1 inhibits chondrogenic differentiation of mesenchymal progenitor cells by targeting TWIST1
  • TWIST1 and TWIST2 were required for optimal cytokine downregulation during acute and, particularly, chronic NOD2 stimulation of human macrophages
  • indirect binding of TWIST1 to the E-boxes of MAGEA4 promoter sequence and a novel regulatory role of TWIST1 in MAGEA4 upregulation
  • ZHX1 could contribute to glioblastoma progression via the regulations of TWIST1 and SNAI2
  • SPZ1, a newly dscribed molecule, transactivates TWIST1 promoters, and this SPZ1-TWIST axis mediates EMT signaling and exerts significant regulatory effects on tumor oncogenesis
  • KAT5 mediates acetylation at lysine residues of SPZ1 at positions 369 and 374, and of TWIST1 at positions 73 and 76, which are required for SPZ1-TWIST1 complex formation and cancer cell migration
  • cell & other
    activated by thrombin (is required for thrombin-induced angiogenesis as measured by endothelial cell migration)
    induced by hypoxia (its expression in cancer cells is enhanced by hypoxia in a HEPAS1-dependent manner)
    POU2F1 (POU2F1 induced the expression of TWIST1, SNAI1, SNAI2 and ZEB1 genes which are involved in the regulation of epithelial-to-mesenchymal transition (EMT)
    repressed by over-expression of BHLHE41
    corresponding disease(s) ACS3 , BGS2 , ISCC , DEL7P21 , CRS , RBNSS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    in breast carcinoma, gastric and lung cancer with metastasis
    tumoral     --over  
    in gliomas and promotes invasion
    tumoral     --low  
    by hypermethylation is observed frequently in colorectal tumors
    tumoral     --over  
    associated with unfavorable outcomes in patients with colorectal cancer
    tumoral somatic mutation      
    in giant cell tumor of bone, leading to inappropriate TWIST1 downregulation of RUNX2, arrested osteoblastic differentiation, and the maintenance of an immature and neoplastic phenotype (
    constitutional     --other  
    epithelial expression of TWIST1 were disturbed in those placentas with chromosomal aberrations
    constitutional     --over  
    hypomethylation is associated with overexpression of PLS3, GATA6, and TWIST1 in the Sezary Syndrome
    Susceptibility to breast cancer in women with Saethre-Chotzen syndrome
    Variant & Polymorphism
    Candidate gene DNA methylation markers of Gastric cancer (GC), which may serve as useful markers that may identify a distinct subset of GC
    Therapy target
    suppression of esophageal cancer progression potentially by using TWIST1 as a target
    promising therapeutic target against intestinal-type gastric cancer.
  • HIF-1alpha- and TWIST-null mice show similarities in their phenotypes