Affinage

TWIST2

Twist-related protein 2 · UniProt Q8WVJ9

Length
160 aa
Mass
18.1 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TWIST2 (Dermo-1) is a basic helix-loop-helix transcription factor that dimerizes with the ubiquitous bHLH protein E12 to bind E-box (CANNTG) motifs and acts predominantly as a transcriptional repressor that controls mesenchymal lineage decisions across dermis, muscle, bone, and hematopoietic compartments (PMID:7589808, PMID:24971743). Lacking intrinsic activation activity, it represses target loci by recruiting histone deacetylase activity (HDAC-inhibitor-sensitive) and by competing with or directly antagonizing lineage-specifying activators including the myogenic factors MyoD and MEF2, ADD1/SREBP1c, Runx1, and C/EBPα at shared DNA elements (PMID:11809751, PMID:14654692, PMID:19090621, PMID:37761873). At genome scale TWIST2 shapes the epigenetic landscape: it competes with MyoD across the genome to close myogenic loci and open growth/oncogenic loci, and it controls H3K27 acetylation at distal enhancers through physical interaction with the chromatin remodelers SMARCA4 and CHD3, thereby sustaining proliferation and blocking terminal myogenesis in fusion-negative rhabdomyosarcoma (PMID:30975722, PMID:37115930). The same chromatin-remodeling activity drives postnatal maturation of dermal fibroblasts by reorganizing accessibility and H3K27ac (PMID:35584664). In adult skeletal muscle, Twist2 marks a satellite-cell-independent progenitor population that maintains type IIb/x myofibres and holds these progenitors in an undifferentiated state (PMID:28218909). TWIST2 also operates as a context-dependent activator and immune modulator, inducing c-Maf to promote IL-10 while restraining inflammatory cytokines in macrophages—a function gated by release from a PDCD4–TWIST2 complex—and shaping thymocyte selection and CD8 lineage commitment through repression of Nur77 (via nuclear retention of HDAC7) and ThPOK (via a Runx3 complex) (PMID:19090621, PMID:24982420, PMID:27391798, PMID:32424141). TWIST2 protein stability is regulated by ZNF451-mediated SUMOylation at K129, which blocks proteasomal degradation (PMID:33791162). Loss-of-function nonsense mutations cause Setleis syndrome, while recurrent de novo missense mutations in the basic DNA-binding domain (residue Glu75) cause Ablepharon macrostomia and Barber-Say syndromes by altering DNA-binding specificity (PMID:20691403, PMID:26119818).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1995 High

    Established the founding biochemical identity of TWIST2 as an E12-dimerizing E-box-binding bHLH factor that represses rather than activates, defining its core molecular mode of action.

    Evidence Yeast two-hybrid, EMSA, and reporter assays defining E12 dimerization and repression of myogenic bHLH proteins

    PMID:7589808

    Open questions at the time
    • Direct target genes in vivo not yet identified
    • Mechanism of repression (cofactor recruitment) not yet defined
  2. 2002 High

    Resolved how TWIST2 represses the myogenic program by mapping the domains that bind MyoD and MEF2 and demonstrating HDAC-dependent chromatin-level repression.

    Evidence Deletion mutagenesis, co-IP, reporter assays, and TSA treatment in transcription assays

    PMID:11809751

    Open questions at the time
    • Specific HDAC isoforms not identified
    • Endogenous target loci not mapped
  3. 2003 High

    Extended TWIST2 repression to lipogenic transcription by showing it binds ADD1/SREBP1c and reduces its DNA binding, linking TWIST2 to adipocyte gene control.

    Evidence Yeast two-hybrid with adipocyte cDNA library, co-IP, reporter assays, HDAC inhibitor dissection

    PMID:14654692

    Open questions at the time
    • In vivo relevance to adipogenesis not tested in this study
    • Shared genomic targets not defined
  4. 2008 High

    Demonstrated in vivo that TWIST2 restrains myeloid lineage output and reprograms cytokine balance, establishing a hematopoietic/immune regulatory role.

    Evidence Twist2-knockout mice with protein-interaction assays against Runx1/C/EBPα and cytokine measurements

    PMID:19090621

    Open questions at the time
    • Direct genomic binding sites for c-Maf activation not mapped here
    • How TWIST2 switches between repression and c-Maf activation unresolved
  5. 2010 High

    Connected TWIST2 to human disease and to its upstream regulation, showing nonsense mutations cause Setleis syndrome and that Wnt/β-catenin drives Dermo1 expression in dermal identity.

    Evidence Homozygosity mapping with EMSA/immunoblot of mutant proteins; conditional β-catenin gain/loss mouse genetics

    PMID:20691403 PMID:20980404

    Open questions at the time
    • Whether truncations are pure loss-of-function or dominant-negative not resolved here
    • Direct β-catenin binding element on Dermo1 not fully defined
  6. 2011 High

    Distinguished the activation versus repression functions of TWIST2 domains by showing the disease mutant Q119X retains dimerization and DNA binding but fails to transactivate periostin.

    Evidence Reporter assays with deletion constructs, EMSA, ChIP, and patient fibroblast analysis

    PMID:21801849

    Open questions at the time
    • Coactivators recruited by the C-terminal domain not identified
    • Generality of activation function beyond periostin unclear
  7. 2013 Medium

    Identified TWIST2 as a direct E-box activator of CD24 driving cancer stem-cell self-renewal, broadening its role to oncogenic transcriptional activation.

    Evidence ChIP of CD24 promoter with overexpression/knockdown and functional assays in HCC cells

    PMID:24193512

    Open questions at the time
    • Single-lab ChIP without genome-wide validation
    • Cofactor basis of activation vs repression context unresolved
  8. 2014 High

    Defined post-transcriptional control of TWIST2 activity in macrophages, showing PDCD4 sequesters TWIST2 and LPS-driven PDCD4 degradation releases it to induce c-Maf/IL-10.

    Evidence Reciprocal co-IP of PDCD4-TWIST2, promoter binding assays, PI3K/mTOR inhibition, LPS stimulation

    PMID:24982420

    Open questions at the time
    • Structural basis of PDCD4-TWIST2 interaction unknown
    • Whether sequestration generalizes beyond macrophages untested
  9. 2014 Medium

    Linked TWIST2 to cell-cycle control in hematopoietic malignancy by showing HLH-dependent direct activation of p21 and epigenetic silencing in AML.

    Evidence Overexpression/knockdown, cell-cycle analysis, promoter methylation analysis in AML samples

    PMID:25088197

    Open questions at the time
    • Direct p21 promoter occupancy not shown by ChIP here
    • Reconciliation of activator role with canonical repression unaddressed
  10. 2015 High

    Established a second mutation class — recurrent de novo basic-domain missense at Glu75 — causing Ablepharon macrostomia and Barber-Say syndromes by altering DNA-binding pattern.

    Evidence Whole exome sequencing, Flag-TWIST2 DNA-binding assays in HeLa, zebrafish expression

    PMID:26119818

    Open questions at the time
    • Precise mechanistic basis (gain vs altered specificity) only partly resolved
    • Affected target gene set in disease tissue not defined
  11. 2015 Medium

    Expanded the macrophage repression mechanism by showing TWIST1/TWIST2 cooperatively remodel cytokine promoter occupancy, recruiting c-Maf/Bmi1 and displacing activators.

    Evidence ChIP of cytokine promoters with siRNA knockdown and c-Maf/Bmi1 rescue in primary human macrophages

    PMID:26019273

    Open questions at the time
    • Direct vs cooperative binding contributions of TWIST2 alone unclear
    • Single-lab ChIP without orthogonal genomic mapping
  12. 2016 Medium

    Demonstrated TWIST2 represses E-cadherin via a defined promoter element downstream of hypoxic HIF-2α signaling, implicating it in EMT.

    Evidence ChIP mapping of E-cadherin promoter, Western blot, siRNA in pancreatic cancer cells

    PMID:26842802

    Open questions at the time
    • Cofactor/HDAC involvement at E-cadherin not dissected
    • Direct HIF-2α-to-TWIST2 mechanistic link incomplete
  13. 2016 High

    Placed TWIST2 in T-cell selection by showing NFATc3-driven induction and TWIST2-dependent repression of Nur77 via nuclear retention and recruitment of HDAC7.

    Evidence Twist2-KO and transgenic mice, ChIP of Nur77 promoter, calcineurin/JNK inhibition, apoptosis assays

    PMID:27391798

    Open questions at the time
    • Direct HDAC7-TWIST2 binding interface not mapped
    • Generalization to peripheral T cells untested
  14. 2017 High

    Defined a distinct adult muscle stem-cell function, identifying Twist2+ progenitors outside the basal lamina that maintain type IIb/x fibres and stay undifferentiated under Twist2 control.

    Evidence Inducible lineage tracing, diphtheria-toxin ablation, in vitro myogenesis, imaging in mice

    PMID:28218909

    Open questions at the time
    • Transcriptional targets sustaining the undifferentiated state not mapped
    • Relationship to satellite-cell signaling unclear
  15. 2017 Medium

    Clarified disease genetics by showing basic-domain mutations act through a predominantly dominant-negative mechanism via a graded allelic series in the ortholog.

    Evidence C. elegans hlh-8 allelic series mutagenesis with expression and phenotype readouts

    PMID:28369379

    Open questions at the time
    • Dominant-negative mechanism inferred in ortholog, not human TWIST2 directly
    • Molecular basis of interference with wild-type dimers not shown
  16. 2017 Medium

    Added metastasis-promoting activator function via a TWIST2→miR-221-3p→THBS2 axis and implicated non-coding upstream regulation in pigmentation phenotypes.

    Evidence ChIP and luciferase assays for miR-221-3p (cervical cancer); WGS/CNV with transgenic zebrafish neural-crest expression

    PMID:28658273 PMID:29242498

    Open questions at the time
    • Single-lab promoter assays
    • Causal regulatory element architecture upstream of TWIST2 incompletely defined
  17. 2019 High

    Provided the genome-wide mechanism by which TWIST2 reprograms cell fate, competing with MyoD to redirect chromatin accessibility from myogenic to oncogenic loci.

    Evidence Inducible expression with ChIP-seq, ATAC-seq, RNA-seq, and knockdown in rhabdomyosarcoma cells

    PMID:30975722

    Open questions at the time
    • Chromatin-remodeling cofactors mediating opening/closing not yet identified here
    • Determinants of locus-specific opening vs closing unclear
  18. 2019 Medium

    Extended the HDAC-repression theme by showing TWIST factors transcriptionally induce HDAC1/HDAC3 to deacetylate cytokine promoters during macrophage tolerance.

    Evidence ChIP of HDAC1/HDAC3 promoters, siRNA knockdown and rescue, histone acetylation assays in human macrophages

    PMID:31028123

    Open questions at the time
    • TWIST2-specific (vs TWIST1) contribution not isolated
    • Single-lab ChIP without genome-wide confirmation
  19. 2019 Medium

    Identified upstream transcriptional regulators of TWIST2 and a hepatic anti-inflammatory output via NF-κB inhibition and FGF21 de-repression.

    Evidence ChIP on Twist2 and FGF21 promoters with overexpression/knockdown and in vivo mouse knockdown

    PMID:31648561

    Open questions at the time
    • Mechanism of NF-κB nuclear translocation block not defined
    • Single-lab data
  20. 2020 High

    Revealed a partner-dependent lineage decision in which TWIST2-Runx3 complexes block ThPOK at its silencer to drive CD8 commitment.

    Evidence Multiple genetic mouse models with Twist2-Runx3 interaction and ThPOK silencer binding assays

    PMID:32424141

    Open questions at the time
    • Structural basis of TWIST2-Runx3 complex unknown
    • Whether HDAC recruitment is involved untested
  21. 2021 Medium

    Defined post-translational stabilization of TWIST2 by ZNF451-mediated SUMOylation at K129 that blocks proteasomal degradation and promotes EMT.

    Evidence Co-IP, SUMOylation assays, K129 mutagenesis, ZNF451 manipulation in mammary epithelial cells

    PMID:33791162

    Open questions at the time
    • Single-lab biochemistry
    • In vivo relevance of K129 SUMOylation untested
  22. 2022 High

    Showed TWIST2 drives postnatal dermal fibroblast maturation through chromatin remodeling, with its loss preserving regenerative chromatin states.

    Evidence Single-cell transcriptomics, ATAC-seq, ChIP-seq, genetic Twist2 deletion, HDAC inhibitor treatment

    PMID:35584664

    Open questions at the time
    • Direct cofactors mediating remodeling not identified here
    • Reversibility of the maturation program unexplored
  23. 2023 High

    Identified the chromatin-remodeling partners (SMARCA4, CHD3) through which TWIST2 controls enhancer H3K27ac to sustain oncogenic growth and block myogenesis in FN-RMS.

    Evidence Reciprocal co-IP, H3K27ac ChIP-seq, RNA-seq, shRNA knockdown, mouse xenograft

    PMID:37115930

    Open questions at the time
    • How TWIST2 selects activating vs repressive enhancers not resolved
    • Stoichiometry of the TWIST2-SMARCA4-CHD3 assembly unknown
  24. 2023 Medium

    Defined TWIST2 as a negative regulator of adipocyte differentiation through temporal chromatin/transcription remodeling, with KO mice showing reduced lipid storage; and reaffirmed direct ADD1/SREBP1c competition at a shared E-box (CHRDL1).

    Evidence ATAC-seq/PRO-seq network analysis and KO mice (adipocyte); EMSA competition and reporter assays with WT vs Q119X (CHRDL1)

    PMID:36810156 PMID:37761873

    Open questions at the time
    • Direct adipogenic target genes not pinpointed
    • Single-lab biochemistry for CHRDL1 competition
  25. 2025 Medium

    Extended TWIST2 repression to mitochondrial quality control and epithelial identity, repressing Bnip3 (renal injury/mitophagy) and being repressed by HOXA10 to restrain EMT in endometrium.

    Evidence RNAi in mice/HK-2 cells with promoter binding and mitophagy assays; CUT&RUN, transcriptomics, siRNA, and mouse implantation model

    PMID:39918659 PMID:41213962

    Open questions at the time
    • Direct ChIP-grade binding mapping limited
    • Single-lab studies for each axis

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TWIST2 toggles between transcriptional repression and activation at different loci and cell contexts — including the structural determinants of cofactor (HDAC, SMARCA4/CHD3, Runx3) selection and the rules governing locus-specific chromatin opening vs closing — remains unresolved.
  • No structural model of TWIST2-cofactor complexes
  • Determinants of activator vs repressor switching not defined
  • Integration of post-translational control (SUMOylation) with genomic targeting unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0140110 transcription regulator activity 4 GO:0042393 histone binding 3
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-168256 Immune System 4 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1643685 Disease 2
Partners
ADD1/SREBP1CCHD3E12MEF2MYODPDCD4RUNX3SMARCA4

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Dermo-1 (TWIST2) is a bHLH protein that dimerizes with the ubiquitous bHLH protein E12 to bind E-box consensus sequences (CANNTG), but lacks detectable transcriptional activation activity; instead it represses transcriptional activity of myogenic bHLH proteins. Yeast two-hybrid screening, electrophoretic mobility shift assay (EMSA), transcriptional reporter assays Developmental biology High 7589808
2002 TWIST2 (Dermo-1) represses MyoD-mediated transactivation through its HLH and C-terminal domains, directly interacts with MEF2 via its N- and C-terminal domains (but not the bHLH domain) to selectively repress the MEF2 transactivation domain, and recruits histone deacetylase activity to mediate chromatin-level repression (trichostatin A treatment reduces repression activity). Deletion mutagenesis of Dermo-1, transcriptional reporter assays, co-immunoprecipitation/direct protein interaction assays, HDAC inhibitor treatment The Journal of biological chemistry High 11809751
2003 TWIST2 physically interacts with ADD1/SREBP1c (identified by yeast two-hybrid and confirmed by co-immunoprecipitation) and represses ADD1/SREBP1c transcriptional activity primarily by reducing its DNA binding to target sequences; this repression is partially dependent on HDAC activity. Yeast two-hybrid with adipocyte cDNA library, co-immunoprecipitation, transcriptional reporter assays, HDAC inhibitor treatment Nucleic acids research High 14654692
2008 TWIST2 inhibits the proliferation and differentiation of granulocyte-macrophage progenitors by interacting with and inhibiting the transcription factors Runx1 and C/EBPα; it also activates c-Maf transcription to promote IL-10 production while inhibiting IL-12 and IFNγ production; Twist2-deficient mice show marked increases in macrophages, neutrophils, and basophils. Twist-2 knockout mice, mechanistic studies with protein-protein interaction assays, gene expression analysis, cytokine measurements PLoS biology High 19090621
2010 Homozygous nonsense mutations in TWIST2 (c.324C>T [p.Q65X] and c.486C>T [p.Q119X]) cause Setleis syndrome; the expressed truncated mutant proteins are unstable and fail to bind DNA normally as shown by electrophoretic mobility shift assays and immunoblot analysis. Homozygosity mapping, gene sequencing, EMSA, immunoblot analysis of mutant proteins American journal of human genetics High 20691403
2010 Canonical Wnt signaling/β-catenin is required and sufficient for Dermo1 (TWIST2) expression and dermal cell identity in the cranium; Dermo1 can be a direct transcriptional target of Wnt/β-catenin signaling in dermal precursors. Genetic fate mapping and conditional β-catenin gain/loss-of-function in mice, reporter gene assays Development (Cambridge, England) High 20980404
2011 TWIST2 nonsense mutation Q119X maintains nuclear localization and homo/heterodimer formation with E12 and DNA binding, but fails to transactivate the periostin gene; the C-terminal domain of TWIST2 is required for proper transactivation and is associated with higher histone acetylation across the periostin 5'-regulatory region. Reporter gene assays with deletion constructs, EMSA, chromatin immunoprecipitation (ChIP), functional analysis in patient fibroblasts The international journal of biochemistry & cell biology High 21801849
2013 TWIST2 directly binds to the E-box region in the CD24 promoter to activate CD24 expression; Twist2-mediated promotion of liver cancer stem-like cell self-renewal operates through a CD24-STAT3-Nanog pathway. Chromatin immunoprecipitation (ChIP) of CD24 promoter, stable Twist2 overexpression and knockdown in HCC cells, in vitro/in vivo functional assays Carcinogenesis Medium 24193512
2014 LPS promotes PDCD4 degradation via PI3K/mTOR pathway, releasing TWIST2 from a PDCD4-TWIST2 complex; free TWIST2 then binds the c-Maf promoter to induce c-Maf mRNA and downstream IL-10 production in macrophages. Co-immunoprecipitation of PDCD4-TWIST2 complex, promoter binding assays, PI3K/mTOR inhibitor treatment, macrophage stimulation with LPS The Journal of biological chemistry High 24982420
2014 TWIST2 directly activates p21 transcription (requiring intact HLH domain) in human hematopoietic cells; overexpression inhibits AML cell growth partially through p21 induction, while hypermethylation of the TWIST2 promoter silences both TWIST2 and p21 in AML patients. Overexpression and knockdown experiments, cell cycle analysis, promoter methylation analysis (pyrosequencing/COBRA), gene expression microarray Oncogene Medium 25088197
2015 Recurrent de novo missense mutations in the basic domain of TWIST2 (at residue Glu75) cause Ablepharon macrostomia syndrome (Lys substitution) or Barber-Say syndrome (Gln or Ala substitution); these mutations alter the DNA-binding pattern of TWIST2 in HeLa cells. Whole exome sequencing, candidate gene sequencing, functional validation of Flag-TWIST2 DNA binding in HeLa cells, zebrafish expression studies American journal of human genetics High 26119818
2015 TWIST1 and TWIST2 bind to cytokine promoters during chronic NOD2 stimulation; they cooperate to enhance binding of c-Maf and Bmi1 to cytokine promoters while decreasing binding of transcriptional activators (ATF4, C/EBPα, Runx1, Runx2), thereby mediating cytokine downregulation in human macrophages. Chromatin immunoprecipitation of cytokine promoters, siRNA knockdown in primary human macrophages, rescue experiments with c-Maf and Bmi1 restoration Journal of immunology Medium 26019273
2016 TWIST2 directly binds the E-cadherin promoter at the -714 bp region (but not the -295 bp region) to repress E-cadherin transcription; HIF-2α promotes EMT in pancreatic cancer by regulating Twist2 binding to the E-cadherin promoter. Chromatin immunoprecipitation (ChIP) assay, Western blot, siRNA knockdown Journal of experimental & clinical cancer research Medium 26842802
2017 TWIST2 transcription factor directly binds the promoter of miR-221-3p to promote its expression; miR-221-3p then targets THBS2 mRNA to suppress its expression, forming a TWIST2→miR-221-3p→THBS2 axis promoting cervical cancer lymphatic metastasis. Chromatin immunoprecipitation (ChIP), luciferase reporter assays, miR-221-3p overexpression/inhibition in vitro and in vivo Cell death & disease Medium 29242498
2017 Lineage tracing reveals Twist2-expressing progenitor cells reside outside the basal lamina of adult skeletal muscle, are molecularly and anatomically distinct from Pax7+ satellite cells, contribute specifically to type IIb/x myofibres, and their genetic ablation causes wasting of type IIb myofibres; Tw2 expression maintains progenitors in an undifferentiated state. Tamoxifen-inducible lineage tracing (Twist2-CreERT2 x reporter mice), genetic ablation (diphtheria toxin), in vitro myogenesis assays, immunofluorescence, electron microscopy Nature cell biology High 28218909
2017 De novo mutations at TWIST2 Glu117 (equivalent residue to TWIST1 Glu117) in the basic DNA-binding domain act via a predominantly dominant-negative mechanism as demonstrated by allelic series in C. elegans hlh-8, showing graded severity in gene expression and cellular phenotype. Targeted mutagenesis of C. elegans hlh-8 allelic series, gene expression analysis, cellular phenotype assessment Human molecular genetics Medium 28369379
2019 TWIST2 competes with MyoD at shared DNA motifs genome-wide (revealed by ChIP-seq) to direct global gene transcription and repression of the myogenic program; TWIST2 shapes the epigenetic landscape by driving chromatin opening at oncogenic loci and chromatin closing at myogenic loci, thereby redirecting MyoD binding from myogenic genes toward oncogenic/metabolic/growth genes in rhabdomyosarcoma. Inducible Twist2 expression system, genome-wide ChIP-seq, RNA-seq, ATAC-seq, knockdown in RMS cells Genes & development High 30975722
2019 Chronic NOD2 stimulation upregulates Twist1/Twist2, which bind to promoters of HDAC1 and HDAC3 to induce their expression; HDAC1 and HDAC3 then mediate histone deacetylation at cytokine promoters, resulting in cytokine downregulation (macrophage memory/tolerance). Chromatin immunoprecipitation of HDAC1/HDAC3 promoters, siRNA knockdown in primary human macrophages, histone acetylation assays, rescue experiments Journal of immunology Medium 31028123
2016 In positively selected thymocytes, TWIST2 expression is induced via the Ca2+-Calcineurin-NFATc3 pathway; stronger TCR signals activating the JNK pathway abolish NFATc3-dependent Twist2 induction. Twist2 determines thymocyte sensitivity to TCR-mediated apoptosis by repressing Nur77 expression; mechanistically, Twist2 retains HDAC7 in the nucleus and recruits it to the Nur77 promoter. Twist2-deficient and transgenic mice, ChIP of Nur77 promoter, pharmacological pathway inhibition (calcineurin, JNK inhibitors), apoptosis assays Cell death and differentiation High 27391798
2020 During CD8 T-cell lineage differentiation, TWIST2 interacts with Runx3 and the complex binds to the silencer region of the ThPOK locus to block ThPOK expression, thereby promoting CD8+ thymocyte differentiation. Twist2-deficient mice, MHC class II-/- and TCR transgenic mouse models, protein-protein interaction assays (Twist2-Runx3), chromatin binding assays at ThPOK silencer Cell death and differentiation High 32424141
2021 ZNF451, a SUMO2/3-specific E3 ligase, directly binds TWIST2 and SUMOylates it at K129, thereby blocking ubiquitin-proteasome-dependent degradation and stabilizing TWIST2 protein to promote EMT. Co-immunoprecipitation, SUMOylation assays, site-directed mutagenesis (K129), ZNF451 overexpression/depletion in mammary epithelial cells, Western blot American journal of cancer research Medium 33791162
2022 TWIST2 drives postnatal maturation of papillary dermal fibroblasts through extensive chromatin remodeling; genetic deletion of Twist2 in dermal fibroblasts delays the postnatal loss of regenerative ability, which is characterized by decreased H3K27ac levels and decreased chromatin accessibility. Single-cell transcriptomics, ATAC-seq, ChIP-seq, genetic Twist2 deletion in dermal fibroblasts, HDAC inhibitor treatment Cell reports High 35584664
2023 TWIST2 controls H3K27 acetylation at distal enhancers in fusion-negative rhabdomyosarcoma by interacting with chromatin remodelers SMARCA4 and CHD3, activating growth-related target genes and repressing myogenesis-related target genes; TWIST2 knockdown enables FN-RMS cells to exit the cell cycle and undergo terminal myogenesis. Co-immunoprecipitation of TWIST2 with SMARCA4 and CHD3, ChIP-seq for H3K27ac, RNA-seq, shRNA knockdown, mouse xenograft model Science advances High 37115930
2023 TWIST2 acts as a negative regulator of adipocyte differentiation in 3T3-L1 and primary preadipocytes; Twist2 knockout mice have compromised lipid storage in subcutaneous and brown adipose tissue. Kinetic ATAC-seq and PRO-seq (nascent transcription) network analysis, Twist2 knockout mice, adipocyte differentiation assays Genome research Medium 36810156
2012 TWIST2 overexpression in chick limb bud (RCAS-mediated) causes hypoplastic limb phenotypes through premature termination of limb outgrowth; TWIST2 directly represses Grem1 expression via a regulatory element downstream of the Grem1 open reading frame, thereby downregulating the Shh/Grem1/Fgf autoregulatory loop; co-expression of Grem1 rescues the Twist2 overexpression phenotype. RCAS retroviral misexpression in chick limb, in situ hybridization, direct regulatory element analysis (reporter/binding assays), genetic rescue with Grem1 co-expression Developmental biology Medium 22884497
2014 The first TWIST2 missense mutation (p.Leu109Pro) causing Setleis syndrome is predicted by in silico modeling to increase unfavorable force field energy; the proline substitution is located near the dimer interface and is predicted to hinder dimer formation, thereby preventing TWIST2 from binding target genes. Homozygosity mapping, gene sequencing, in silico structural modeling on crystallographically generated dimer Clinical genetics Low 25410422
2019 KLF15 directly interacts with the Twist2 promoter to activate TWIST2 expression; SREBP1c and FOXO1 repress TWIST2 expression; TWIST2 overexpression inhibits NF-κB nuclear translocation and binding to the FGF21 promoter, thereby de-repressing FGF21 expression to ameliorate hepatic steatosis. ChIP assays on Twist2 and FGF21 promoters, TWIST2 overexpression and knockdown in hepatocytes, in vivo mouse knockdown model FASEB journal Medium 31648561
2023 TWIST2 and ADD1/SREBP1c compete for binding to the same E-box in the CHRDL1 gene upstream region; TWIST2 (but not TWIST2-Q119X mutant) blocks ADD1/SREBP1c-mediated activation of CHRDL1, while the Q119X mutant may form an inactive complex with ADD1/SREBP1c that allows other activators to increase CHRDL1 expression. EMSA (homo/heterodimer binding assays), EMSA competition assays, luciferase reporter assays, patient fibroblast/lymphoblast expression analysis Genes Medium 37761873
2025 TWIST2 directly inhibits Bnip3 transcriptional activity by binding the Bnip3 promoter; TWIST2 knockdown alleviates renal ischemia-reperfusion injury by improving mitochondrial function and enhancing mitophagy through de-repression of Bnip3. RNAi knockdown in mice and HK-2 cells, promoter binding assay (luciferase/ChIP implied), mitochondrial function assays, autophagy markers, electron microscopy Human cell Medium 39918659
2025 HOXA10 directly represses TWIST2 in endometrial luminal epithelium; HOXA10 loss de-represses TWIST2 to induce partial EMT and increased cell motility; TWIST2 knockdown restores epithelial identity and impairs embryo implantation; CUT&RUN and transcriptomic profiling confirm HOXA10 directly activates epithelial gene networks and represses mesenchymal programs including TWIST2. CUT&RUN, transcriptomic profiling, siRNA knockdown of HOXA10 and TWIST2 in human endometrial cells, in vivo mouse implantation model Cell death discovery Medium 41213962
2014 TWIST2 promotes survival of ovarian cancer cells under hypoxic conditions through activation of Akt (PI3K-Akt pathway); Twist2-overexpressing cells show increased Akt phosphorylation under DFO-induced hypoxic stress, reducing apoptosis. Stable Twist2 overexpression in SKOV-3 cells, DFO-induced hypoxia simulation, flow cytometry for apoptosis, Western blot for Akt phosphorylation Oncology letters Low 23946798
2009 TWIST2 downregulates CD7 gene promoter activity through its C-terminal domain, and recruits histone deacetylase activity (sensitive to TSA and sodium butyrate); ectopic Twist2 expression in Jurkat cells reduces galectin-1-induced apoptosis. Promoter reporter assays with C-terminal deletion mutants, HDAC inhibitor treatment (TSA, sodium butyrate), ectopic Twist2 expression, apoptosis assays Molecules and cells Medium 19937140
2014 TWIST2 downregulation in Twist2-siRNA-treated ovarian cancer cells sensitizes them to cisplatin; conversely, TWIST2 overexpression promotes cisplatin resistance through the AKT/GSK-3β signaling pathway. Plasmid overexpression and siRNA knockdown in OV2008/C13K cells, cell viability assays, apoptosis analysis, Western blot for pAKT/pGSK-3β Oncology letters Low 24944676
2017 A structural variant (quadruplication of a 6 kb non-coding sequence ~16 kb upstream of TWIST2) causes aberrant TWIST2 expression during neural crest development; ectopic expression of bovine TWIST2 in neural crest in transgenic zebrafish leads to decreased melanocyte numbers, implicating TWIST2 in regulating pigmentation. Whole genome sequencing, copy number variant analysis, transgenic zebrafish with ectopic TWIST2 expression in neural crest PloS one Medium 28658273
2010 In osteoblastic cells, Twist2 haploinsufficiency reduces Fgf2 and Fgfr1-4 expression; both Twist1 and Twist2 stimulate 4.9 kb Fgfr2 promoter activity in the presence of the Twist binding partner E12, indicating TWIST2 directly regulates FGF signaling components. Conditional haploinsufficient mouse model (Twist1f/+;Twist2Cre/+), dual luciferase reporter assays with E12, in situ hybridization, real-time PCR PloS one Medium 24971743

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Dermo-1: a novel twist-related bHLH protein expressed in the developing dermis. Developmental biology 231 7589808
2011 Twist2 contributes to breast cancer progression by promoting an epithelial-mesenchymal transition and cancer stem-like cell self-renewal. Oncogene 168 21602879
2010 Redundant or separate entities?--roles of Twist1 and Twist2 as molecular switches during gene transcription. Nucleic acids research 144 20935057
2017 A Twist2-dependent progenitor cell contributes to adult skeletal muscle. Nature cell biology 118 28218909
2017 MicroRNA-221-3p, a TWIST2 target, promotes cervical cancer metastasis by directly targeting THBS2. Cell death & disease 87 29242498
2013 Down-regulation of miR-138 promotes colorectal cancer metastasis via directly targeting TWIST2. Journal of translational medicine 80 24171926
2005 TWIST2 demonstrates differential methylation in immunoglobulin variable heavy chain mutated and unmutated chronic lymphocytic leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 74 15809452
2000 Human Dermo-1 has attributes similar to twist in early bone development. Bone 73 11062344
2016 HIF-2α promotes epithelial-mesenchymal transition through regulating Twist2 binding to the promoter of E-cadherin in pancreatic cancer. Journal of experimental & clinical cancer research : CR 69 26842802
2002 Dermo-1, a multifunctional basic helix-loop-helix protein, represses MyoD transactivation via the HLH domain, MEF2 interaction, and chromatin deacetylation. The Journal of biological chemistry 64 11809751
2011 Correlation of TWIST2 up-regulation and epithelial-mesenchymal transition during tumorigenesis and progression of cervical carcinoma. Gynecologic oncology 62 22018873
2013 Twist2 promotes self-renewal of liver cancer stem-like cells by regulating CD24. Carcinogenesis 61 24193512
2010 Role of canonical Wnt signaling/ß-catenin via Dermo1 in cranial dermal cell development. Development (Cambridge, England) 61 20980404
2008 Twist-2 controls myeloid lineage development and function. PLoS biology 58 19090621
2016 Twist2 promotes kidney cancer cell proliferation and invasion by regulating ITGA6 and CD44 expression in the ECM-receptor interaction pathway. OncoTargets and therapy 57 27099513
2013 The role of nuclear β-catenin accumulation in the Twist2-induced ovarian cancer EMT. PloS one 56 24244294
2010 Homozygous nonsense mutations in TWIST2 cause Setleis syndrome. American journal of human genetics 52 20691403
2014 LPS induces the degradation of programmed cell death protein 4 (PDCD4) to release Twist2, activating c-Maf transcription to promote interleukin-10 production. The Journal of biological chemistry 51 24982420
2003 Twist2, a novel ADD1/SREBP1c interacting protein, represses the transcriptional activity of ADD1/SREBP1c. Nucleic acids research 49 14654692
2015 Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes. American journal of human genetics 47 26119818
2013 Low osteogenic differentiation potential of placenta-derived mesenchymal stromal cells correlates with low expression of the transcription factors Runx2 and Twist2. Stem cells and development 39 23763516
2011 Epigenetic inactivation of TWIST2 in acute lymphoblastic leukemia modulates proliferation, cell survival and chemosensitivity. Haematologica 36 22058208
2019 Twist2 amplification in rhabdomyosarcoma represses myogenesis and promotes oncogenesis by redirecting MyoD DNA binding. Genes & development 34 30975722
2019 Long non-coding RNA CASC9 enhances breast cancer progression by promoting metastasis through the meditation of miR-215/TWIST2 signaling associated with TGF-β expression. Biochemical and biophysical research communications 32 31178137
2010 Potential involvement of Twist2 and Erk in the regulation of osteoblastogenesis by HB-EGF-EGFR signaling. Cell structure and function 31 20448405
2011 Coexpression of hypoxia-inducible factor-2α, TWIST2, and SIP1 may correlate with invasion and metastasis of salivary adenoid cystic carcinoma. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 30 22103974
2014 Twist1- and Twist2-haploinsufficiency results in reduced bone formation. PloS one 29 24971743
1999 Identification of DERMO-1 as a member of helix-loop-helix type transcription factors expressed in osteoblastic cells. Journal of cellular biochemistry 28 10022499
2019 KLF15-activating Twist2 ameliorated hepatic steatosis by inhibiting inflammation and improving mitochondrial dysfunction via NF-κB-FGF21 or SREBP1c-FGF21 pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26 31648561
2012 Significance of heterogeneous Twist2 expression in human breast cancers. PloS one 26 23133563
2010 Isolation of murine bone marrow derived mesenchymal stem cells using Twist2 Cre transgenic mice. Bone 26 20673822
2022 Twist2-driven chromatin remodeling governs the postnatal maturation of dermal fibroblasts. Cell reports 25 35584664
2011 Setleis syndrome in Mexican-Nahua sibs due to a homozygous TWIST2 frameshift mutation and partial expression in heterozygotes: review of the focal facial dermal dysplasias and subtype reclassification. Journal of medical genetics 25 21931173
2020 LINC01235-TWIST2 feedback loop facilitates epithelial-mesenchymal transition in gastric cancer by inhibiting THBS2. Aging 24 33206629
2017 Localized TWIST1 and TWIST2 basic domain substitutions cause four distinct human diseases that can be modeled in Caenorhabditis elegans. Human molecular genetics 24 28369379
2014 Regulation of p21 by TWIST2 contributes to its tumor-suppressor function in human acute myeloid leukemia. Oncogene 24 25088197
2016 RETRACTED: Twist2 promotes kidney cancer cell proliferation and invasion via regulating ITGA6 and CD44 expression in the ECM-Receptor-Interaction pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 23 27261625
2021 ZNF451 stabilizes TWIST2 through SUMOylation and promotes epithelial-mesenchymal transition. American journal of cancer research 22 33791162
2013 Twist2 functions as a tumor suppressor in murine osteosarcoma cells. Cancer science 22 23557174
2015 TWIST1 and TWIST2 regulate glycogen storage and inflammatory genes in skeletal muscle. The Journal of endocrinology 21 25663706
2009 Twist2 regulates CD7 expression and galectin-1-induced apoptosis in mature T-cells. Molecules and cells 21 19937140
2008 Identification of novel genes including Dermo-1, a marker of dermal differentiation, expressed in trout somitic external cells. The Journal of experimental biology 20 18344491
2015 Twist1 and Twist2 Contribute to Cytokine Downregulation following Chronic NOD2 Stimulation of Human Macrophages through the Coordinated Regulation of Transcriptional Repressors and Activators. Journal of immunology (Baltimore, Md. : 1950) 19 26019273
2021 TWIST2 inhibits EMT and induces oxidative stress in lung cancer cells by regulating the FGF21-mediated AMPK/mTOR pathway. Experimental cell research 18 34044016
2011 Nonsense mutations of the bHLH transcription factor TWIST2 found in Setleis Syndrome patients cause dysregulation of periostin. The international journal of biochemistry & cell biology 18 21801849
2019 Role of epithelial-mesenchymal transition regulated by twist basic helix-loop-helix transcription factor 2 (Twist2) in embryo implantation in mice. Reproduction, fertility, and development 17 30779884
2019 Twist1 and Twist2 Induce Human Macrophage Memory upon Chronic Innate Receptor Treatment by HDAC-Mediated Deacetylation of Cytokine Promoters. Journal of immunology (Baltimore, Md. : 1950) 16 31028123
2014 Twist2 contributes to cisplatin-resistance of ovarian cancer through the AKT/GSK-3β signaling pathway. Oncology letters 16 24944676
2014 The indicative function of Twist2 and E-cadherin in HPV oncogene-induced epithelial-mesenchymal transition of cervical cancer cells. Oncology reports 16 25420506
2022 Nicotinamide mononucleotide ameliorates adriamycin-induced renal damage by epigenetically suppressing the NMN/NAD consumers mediated by Twist2. Scientific reports 15 35962139
2018 Identification of a multipotent Twist2-expressing cell population in the adult heart. Proceedings of the National Academy of Sciences of the United States of America 14 30127033
2017 A structural variant in the 5'-flanking region of the TWIST2 gene affects melanocyte development in belted cattle. PloS one 13 28658273
2023 Kinetic networks identify TWIST2 as a key regulatory node in adipogenesis. Genome research 12 36810156
2023 TWIST2-mediated chromatin remodeling promotes fusion-negative rhabdomyosarcoma. Science advances 12 37115930
2021 Prostaglandin D2 synthase/prostaglandin D2/TWIST2 signaling inhibits breast cancer proliferation. Anti-cancer drugs 12 34232948
2017 Male germline recombination of a conditional allele by the widely used Dermo1-cre (Twist2-cre) transgene. Genesis (New York, N.Y. : 2000) 12 28722198
2014 Setleis syndrome: clinical, molecular and structural studies of the first TWIST2 missense mutation. Clinical genetics 12 25410422
2012 Twist2 contributes to termination of limb bud outgrowth and patterning through direct regulation of Grem1. Developmental biology 12 22884497
2016 Expression of Twist2 is controlled by T-cell receptor signaling and determines the survival and death of thymocytes. Cell death and differentiation 11 27391798
2021 MIR205 host gene (MIR205HG) drives osteosarcoma metastasis via regulating the microRNA 2114-3p (miR-2114-3p)/twist family bHLH transcription factor 2 (TWIST2) axis. Bioengineered 10 33949284
2021 Zebrafish twist2/dermo1 regulates scale shape and scale organization during skin development and regeneration. Cells & development 10 33994357
2013 A novel frameshift mutation in TWIST2 gene causing Setleis syndrome. Indian journal of pediatrics 10 24127007
2010 Twist2: role in corneal stromal keratocyte proliferation and corneal thickness. Investigative ophthalmology & visual science 10 20574024
2006 Analysis of scleraxis and dermo-1 genes in a regenerating limb of Xenopus laevis. Developmental dynamics : an official publication of the American Association of Anatomists 10 16470627
2018 Twist2 and CD24 expression alters renal microenvironment in obesity associated kidney cancer. European review for medical and pharmacological sciences 9 29424894
2013 Twist2 promotes ovarian cancer cell survival through activation of Akt. Oncology letters 9 23946798
2019 TWIST2: A new candidate tumor suppressor in prostate cancer. The Prostate 8 31433071
2014 Hyperthermia inhibited the migration of tongue squamous cell carcinoma through TWIST2. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 8 25048179
2025 HOXA10-TWIST2 antagonism drives partial epithelial-to-mesenchymal transition for embryo implantation. Cell death discovery 7 41213962
2021 TWIST2 and the PPAR signaling pathway are important in the progression of nonalcoholic steatohepatitis. Lipids in health and disease 7 33879188
2020 Twist2 promotes CD8+ T-cell differentiation by repressing ThPOK expression. Cell death and differentiation 7 32424141
2020 Twist2 is NFkB-responsive when p120-catenin is inactivated and EGFR is overexpressed in esophageal keratinocytes. Scientific reports 7 33139779
2014 The effects of Twist-2 on liver endotoxin tolerance induced by a low dose of lipopolysaccharide. Inflammation 7 24005898
2025 Decabromodiphenyl ethane induces intrauterine growth restriction by suppressing placental angiogenesis via TWIST2/NAT10-mediated ac4C-dependent TGF-β1 mRNA stabilization. Journal of hazardous materials 5 40749657
2022 Expression of Dickkopf-1 and Twist2 in Cervical Squamous Cell Carcinoma and Their Correlation with Vasculogenic Mimicry. Journal of healthcare engineering 5 35340228
2022 Twist2 Reduced NLRP3-Induced Inflammation of Infantile Pneumonia via Regulation of Mitochondrial Permeability Transition by FOXO1. International archives of allergy and immunology 5 35700708
2022 The Elevated Circ_0067835 Could Accelerate Cell Proliferation and Metastasis via miR-1236-3p/Twist2 Axis in Hepatocellular Carcinoma. BioMed research international 5 36262967
2022 Twist2-expressing cells reside in human skeletal muscle and are responsive to aging and resistance exercise training. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 5 36374263
2019 Asymmetric Division Gene Neurl2 Mediates Twist2 Regulation of Self-Renewal of Mouse Lewis Lung Cancer Stem Cells. Journal of Cancer 5 31293641
2018 Clinical Description, Molecular Analysis of TWIST2 Gene, and Surgical Treatment in a Patient With Barber-Say Syndrome. Ophthalmic plastic and reconstructive surgery 5 29329175
2017 Twist2 Is Upregulated in Early Stages of Repair Following Acute Kidney Injury. International journal of molecular sciences 5 28208580
2013 Aneuploidy facilitates oncogenic transformation via specific genetic alterations, including Twist2 upregulation. Carcinogenesis 5 23689353
2011 Differential methylation of CpG islands within the dermo1 gene promoter in several cancer cell lines. Oncology reports 5 21109964
2025 HDAC4 super-enhancer drives CEBPB-mediated TWIST2 transcription to promote chemoresistance in LUAD. Cancer letters 4 40222483
2024 Twist2 contributes to skin regeneration and hair follicle formation in mouse fetuses. Scientific reports 4 38740788
2018 Upregulation of Twist2 in Non-Muscle Invasive Urothelial Carcinoma of the Bladder Correlate with Response to Treatment and Progression. Open access Macedonian journal of medical sciences 4 29983794
2015 Biological function and molecular mechanism of Twist2. Yi chuan = Hereditas 4 25608809
2009 Enhanced generation of myeloid lineages in hematopoietic differentiation from embryonic stem cells by silencing transcriptional repressor Twist-2. Cloning and stem cells 4 20025523
2025 Twist2 knockdown alleviates renal ischemia-reperfusion injury by maintaining mitochondrial function and enhancing mitophagy through Bnip3. Human cell 3 39918659
2022 Single Nucleotide Polymorphism of TWIST2 May Be a Modifier for the Association between High-Density Lipoprotein Cholesterol and Blood Lead (Pb) Level. International journal of environmental research and public health 3 35162374
2021 Expression Profiling Identifies TWIST2 Target Genes in Setleis Syndrome Patient Fibroblast and Lymphoblast Cells. International journal of environmental research and public health 3 33669496
2017 Barber-say syndrome: a confirmed case of TWIST2 gene mutation. Clinical case reports 3 28680619
2021 Ocular adnexal phenotype and management of a patient with mosaic expression of a mutation in TWIST2. Orbit (Amsterdam, Netherlands) 2 34092176
2017 [Expression and mechanism of Twist2 in glioma]. Zhonghua bing li xue za zhi = Chinese journal of pathology 2 29224276
2017 TWIST2 EXPRESSIONS IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE URINARY BLADDER SHOWED DOWN REGULATION CORRELATED WITH GOOD SURVIVAL AND LOW INCIDENCE OF DISTANT METASTASIS. Journal of the Egyptian Society of Parasitology 2 30157337
2023 Mechanisms of Regulation of the CHRDL1 Gene by the TWIST2 and ADD1/SREBP1c Transcription Factors. Genes 1 37761873
2025 The Role of Twist2 in Myoblast Proliferation, Fusion, and Its Impact on Muscle Structure During the Growth of Chinese Perch (Siniperca chuatsi). Animals : an open access journal from MDPI 0 40282011
2025 Lineage tracing of Twist2-expressing cells in mouse taste buds. Journal of oral biosciences 0 41714028
2024 Comparative Analysis of Transcription Factors TWIST2, GATA3, and HES5 in Glioblastoma Multiforme : Evaluating Biomarker Potential and Therapeutic Targets Using in Silico Methods. Journal of Korean Neurosurgical Society 0 39444320
2023 Retracted: Expression of Dickkopf-1 and Twist2 in Cervical Squamous Cell Carcinoma and Their Correlation with Vasculogenic Mimicry. Journal of healthcare engineering 0 37621628

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