Affinage

TCF21

Transcription factor 21 · UniProt O43680

Length
179 aa
Mass
19.7 kDa
Annotated
2026-06-10
100 papers in source corpus 43 papers cited in narrative 44 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

TCF21 is a class II basic helix-loop-helix transcription factor that controls mesenchymal cell-fate determination, fibroblast specification, and phenotypic plasticity across cardiovascular, renal, gonadal, and tumor contexts, binding the canonical E-box CAGCTG and frequently overlapping AP-1 (JUN/JUND) loci in target enhancers (PMID:26020271, PMID:34148307). In the developing heart it is essential for specifying cardiac fibroblast progenitors and their epithelial-to-mesenchymal transition from the epicardium, while restraining differentiation of epicardium-derived cells toward smooth muscle (PMID:22573622, PMID:22687751). In vascular smooth muscle, TCF21 drives phenotypic modulation toward a fibroblast-like 'fibromyocyte' state that populates the atherosclerotic fibrous cap, acting as a transcriptional repressor of the SMC differentiation program: it suppresses and physically binds MYOCD to block MYOCD-SRF complex formation, and it antagonizes SMAD3 by locally restricting chromatin accessibility at shared binding sites (PMID:26020946, PMID:31815603, PMID:31359001, PMID:30307970). Beyond the vasculature, TCF21 acts downstream of SRY through SRY/SOX9 promoter elements to initiate Sertoli cell differentiation via a SRY→TCF21→SCX cascade (PMID:21637323, PMID:23034159), and is required for specification of Foxd1+ renal stromal progenitors, whose loss causes stromal depletion, emergence of profibrotic populations, and interstitial fibrosis (PMID:39589156, PMID:41632505). TCF21 expression is set epigenetically: the lncRNA TARID recruits GADD45A and the TET/base-excision-repair machinery to demethylate the TCF21 promoter (PMID:25087872), a circuit silenced by aberrant promoter methylation in cancer where TCF21 acts as a tumor suppressor (PMID:16415157). A coronary-disease-associated polymorphism (rs12190287) tunes TCF21 levels through both disruption of an enhancer AP-1 element and allele-specific miR-224 binding in its 3'-UTR (PMID:24676100, PMID:23874238). TCF21 protein is stabilized and rendered a more potent repressor by SUMO1 sumoylation at K24, which enhances HDAC1/2 recruitment and is reversed by SENP1 (PMID:27028856). Its direct transcriptional outputs are context-specific, including activation of the metastasis suppressor KISS1 (PMID:21771727), repression of MYOCD/SRF and SMAD3 targets in SMCs (PMID:31815603, PMID:30307970), direct regulation of ECM and PDGFRB-ERK genes (COL1A1, COL3A1, PDGFRB) driving cardiac fibroblast activation (PMID:40753125, PMID:41926244), and activation of LIMK2-cofilin signaling promoting cytoskeletal reorganization and invasion in endometriosis (PMID:41786705).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2006 High

    Established TCF21 as a tumor suppressor silenced by promoter methylation, defining the first disease-relevant mechanism and linking its loss to mesenchymal-to-epithelial transition control.

    Evidence Restriction landmark genomic scanning, methylation-specific PCR, and functional rescue in cell lines and xenografts in lung and head/neck cancer

    PMID:16415157

    Open questions at the time
    • Did not identify direct transcriptional targets mediating suppression
    • Mechanism of MET reversion not defined at the gene level
  2. 2011 Medium

    Identified TCF21 as a direct activator of the metastasis suppressor KISS1 and a partner of E12/TCF12, providing an early molecular handle on its tumor-suppressive transcriptional output.

    Evidence ChIP at KISS1 promoter, co-IP with E12/TCF12, and motility assays in melanoma cells

    PMID:21771727

    Open questions at the time
    • Single lab
    • Whether KISS1 activation generalizes beyond melanoma not established
  3. 2011 High

    Placed TCF21 downstream of SRY in male sex determination, showing SRY directly activates the Tcf21 promoter to drive Sertoli cell differentiation.

    Evidence Promoter reporter mutagenesis, in vivo ChIP of SRY in fetal rat testis, and ovarian cell sex-reversal assays

    PMID:21637323

    Open questions at the time
    • TCF21 direct targets in Sertoli cells not yet mapped at this stage
  4. 2012 High

    Defined TCF21 as essential for cardiac fibroblast specification and EMT from epicardial progenitors while restraining SMC differentiation, establishing its developmental fibroblast-fate role.

    Evidence Tcf21-null and Pod1 knockout mouse genetics, lineage tracing, and retinoic acid manipulation

    PMID:22573622 PMID:22687751

    Open questions at the time
    • Direct transcriptional targets in epicardial EMT not identified
    • Co-repressor partners not yet defined
  5. 2012 Medium

    Mapped genome-wide TCF21 targets in Sertoli cells and defined a SRY→TCF21→SCX differentiation cascade, extending the gonadal program downstream.

    Evidence ChIP-chip target identification and Sry/Tcf21/Scx sex-reversal transfection assays

    PMID:23034159

    Open questions at the time
    • Single lab
    • Direct vs indirect target distinction limited by ChIP-chip resolution
  6. 2013 High

    Provided biochemical evidence that TCF21 functions as a transcriptional repressor by associating with co-repressor complexes during proepicardial lineage determination.

    Evidence Mass-spectrometry interactome of Tcf21 immunoprecipitates plus morpholino depletion in Xenopus

    PMID:23637334

    Open questions at the time
    • Specific co-repressor subunits and target loci not resolved
  7. 2013 High

    Connected the coronary-disease GWAS signal to TCF21 regulation, showing rs12190287 disrupts an enhancer AP-1 element controlling allele-specific expression downstream of PDGFR-β and WT1.

    Evidence Allele-specific luciferase reporters, TF-binding/EMSA, chromatin accessibility, and pathway perturbation in vascular cells

    PMID:23874238

    Open questions at the time
    • Causal in vivo demonstration of the variant effect on disease not established
  8. 2014 High

    Defined the TARID lncRNA–GADD45A–TET–base-excision-repair circuit that activates TCF21 by promoter demethylation, explaining how TCF21 silencing is reversed.

    Evidence RIP, ChIP, bisulfite-seq, BER assays, and TET inhibition in one integrated study

    PMID:25087872

    Open questions at the time
    • Upstream signals controlling TARID expression not defined
  9. 2014 High

    Established a second, post-transcriptional layer of the CAD locus: rs12190287 alters a 3'-UTR miR-224 site, tuning TCF21 response to TGF-β and PDGF allele-specifically.

    Evidence 3'-UTR reporters, kinetic RNA-RNA binding assays, RNA probing, and allelic imbalance in HCASMC

    PMID:23874238 PMID:24676100

    Open questions at the time
    • Relative contribution of enhancer vs 3'-UTR mechanisms to disease risk not quantified
  10. 2015 High

    Defined the canonical TCF21 DNA-binding motif (CAGCTG) genome-wide and showed extensive co-binding with AP-1, framing how TCF21 engages SMC enhancers.

    Evidence ChIP-seq with TCF21/JUN/JUND antibodies and motif/eQTL analysis in HCASMC

    PMID:26020271

    Open questions at the time
    • Whether AP-1 co-binding is cooperative or antagonistic not resolved here
  11. 2015 High

    Demonstrated functionally that TCF21 promotes SMC proliferation/migration, suppresses SMC markers, and contributes vascular cells to the atherosclerotic fibrous cap.

    Evidence siRNA-RNA-Seq, in vitro functional assays, and lineage tracing in ApoE-/- and Ldlr-/- mice

    PMID:26020946

    Open questions at the time
    • Direct repression mechanism of SMC genes not yet defined at this stage
  12. 2015 Medium

    Extended TCF21 repressor function to steroidogenic and metabolic loci, showing E-box-dependent repression of SHP and SF-1.

    Evidence ChIP at SHP promoter and gain-of-function expression analysis in adrenocortical and hepatocarcinoma cells

    PMID:26421305 PMID:26421867

    Open questions at the time
    • Single lab
    • Direct vs indirect SF-1 repression not fully separated
  13. 2016 Medium

    Identified SUMO1 sumoylation at K24 (reversed by SENP1) as a post-translational switch that stabilizes TCF21 and enhances HDAC1/2-dependent repression.

    Evidence Co-IP, K24R mutagenesis, half-life and ChIP/reporter assays at the pS2 promoter

    PMID:27028856

    Open questions at the time
    • Single lab
    • SUMO ligase and physiological signals triggering sumoylation not identified
  14. 2017 Medium

    Showed TCF21 directly controls EMT/migration modality via E-box occupancy at the Slug promoter, linking it to cancer cell phenotypic transitions.

    Evidence ChIP at Slug E-boxes with gene manipulation and live migration imaging in ovarian cancer cells

    PMID:31241128

    Open questions at the time
    • Single lab
    • Whether Slug regulation is activating or repressive context-dependent
  15. 2018 High

    Resolved the TCF21–SMAD3 antagonism in SMCs, showing TCF21 locally blocks chromatin accessibility at SMAD3 sites to oppose SMC differentiation.

    Evidence ChIP-seq, ATAC-seq, RNA-seq and reporter assays in HCASMC

    PMID:30307970

    Open questions at the time
    • Mechanism by which TCF21 reduces accessibility not biochemically defined
  16. 2019 High

    Established the central mechanism of SMC phenotypic modulation: TCF21 antagonizes MYOCD-SRF transcriptionally and by physically binding MYOCD, and SMC-specific deletion blocks fibromyocyte formation in atherosclerosis.

    Evidence ChIP-seq, co-IP, reporter and genome editing assays plus SMC-specific KO and single-cell RNA-seq of mouse and human lesions

    PMID:31359001 PMID:31815603

    Open questions at the time
    • Whether fibromyocyte fate is protective or detrimental in human disease not resolved
  17. 2019 Medium

    Broadened TCF21 function into adipose/lung mesenchymal and fibrotic biology, regulating IL-6, MMP/collagen genes, LPL, and lipofibroblast identity.

    Evidence Loss/gain-of-function with qRT-PCR, zymography, ChIP/luciferase, and lineage tracing in adipose, lung, and preadipocyte models

    PMID:29540474 PMID:30675802 PMID:31065241

    Open questions at the time
    • Single labs per tissue
    • Cross-tissue conservation of these targets unclear
  18. 2019 Medium

    Showed TCF21 suppresses pro-angiogenic and pro-survival signaling (VEGFA/PDGF-BB, PI3K/Akt, ERK1/2) consistent with its tumor-suppressor role.

    Evidence Ectopic expression, conditioned-medium endothelial assays, and signaling Westerns in cholangiocarcinoma

    PMID:30920845

    Open questions at the time
    • Single lab
    • Direct transcriptional targets mediating signaling suppression not identified
  19. 2021 Medium

    Defined TCF21 as a master regulator of fibroblast/pericyte/stromal cell states across cancer and metabolic contexts, including CAF state, adipogenesis via Dlk1/HTR2A, and parietal epithelial cell ploidy via YY1.

    Evidence Overexpression and conditional KO with multiomics (scRNA-seq, ATAC-seq), ChIP-seq, and functional rescue across ovarian CAF, adipose, and renal PEC systems

    PMID:32434219 PMID:34148307 PMID:34872001 PMID:36857185

    Open questions at the time
    • Context-specific direct targets only partially overlapping
    • Single labs per system
  20. 2021 Medium

    Revealed that sumoylation-dependent TCF21–USF2 heterodimers can act as activators (of SF-1 and ER-β) in estrogen-driven endometriosis, showing TCF21 can switch from repressor to activator depending on partner.

    Evidence Co-IP, half-life and ChIP assays at SF-1/ER-β promoters in endometriotic stromal cells

    PMID:33693540

    Open questions at the time
    • Single lab
    • Determinants selecting repressor vs activator complexes unclear
  21. 2023 Medium

    Extended TCF21 regulation and function to fibrosis-relevant tissues, including DNMT3a-mediated promoter methylation in hepatic stellate cells and suppression of TGF-β-driven myofibroblast differentiation rescued by TARID delivery.

    Evidence ChIP, bisulfite-seq, co-IP (hnRNPA1) in HSCs and gain/loss-of-function with EV/lipid-nanoparticle TARID delivery in mouse and porcine MI models

    PMID:36916305 PMID:37268177

    Open questions at the time
    • Single labs
    • Whether TARID therapy effects are fully TCF21-dependent not isolated
  22. 2024 Medium

    Identified additional direct TCF21 targets linking it to cholesterol efflux, decidualization, renal progenitor specification, and tumor immune evasion.

    Evidence ChIP/ChIP-seq and reporter assays (ABCA10, PDE4C, ERO1A) plus conditional KO with multiomics in kidney (Foxd1 lineage)

    PMID:39326465 PMID:39438390 PMID:39589156 PMID:40659157

    Open questions at the time
    • Each target validated in a single context
    • Generality of cholesterol/immune outputs unknown
  23. 2025 High

    Established TCF21 as a direct, context-determinant regulator of fibrosis: it activates ECM/PDGFRB-ERK and LIMK2-cofilin programs to drive fibrosis in some tissues while restraining myofibroblast conversion in others, with in vivo anti-fibrotic effects of cardiac TCF21 overexpression.

    Evidence ChIP-seq, multiple inducible/conditional KO and AAV overexpression mouse models, pharmacological LIMK inhibition, and human snRNA-seq

    PMID:40753125 PMID:41360282 PMID:41632505 PMID:41786705 PMID:41926244

    Open questions at the time
    • Why TCF21 is pro-fibrotic in some fibroblasts but anti-fibrotic in others is unresolved
    • Direct chromatin determinants of the opposite outcomes not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TCF21 selects between transcriptional repression (MYOCD/SRF, SMAD3, ERO1A) and activation (KISS1, ABCA10, LIMK2) at distinct loci, and what cofactor/PTM context dictates pro- versus anti-fibrotic outcomes, remains unresolved.
  • No unifying model of repressor-vs-activator switching
  • Structural basis of partner selection (E12/TCF12, USF2, MYOCD, HDAC1/2) not determined
  • Determinants of tissue-specific fibrosis outcome unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 12 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1266738 Developmental Biology 5 R-HSA-1643685 Disease 5 R-HSA-1474244 Extracellular matrix organization 3
Partners
HDAC1HDAC2HNRNPA1MYOCDSMAD3SUMO1TCF12USF2

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 Tcf21 (bHLH transcription factor) is required for lineage-specific epithelial-to-mesenchymal transition (EMT) of cardiac fibroblast progenitors in the epicardium; Tcf21-null hearts fail to form cardiac fibroblasts, and lineage-traced null cells are unable to undergo EMT, establishing Tcf21 as essential for cardiac fibroblast specification prior to EMT initiation. Tcf21-null mouse genetics, tamoxifen-inducible Cre lineage tracing, histological and immunofluorescence phenotyping Development (Cambridge, England) High 22573622
2012 Pod1 (Tcf21) inhibits differentiation of epicardium-derived cells (EPDCs) into smooth muscle cells in the developing heart; loss of Pod1 results in increased smooth muscle marker expression on the heart surface and a paucity of interstitial fibroblasts, with epicardial EMT relatively unaffected; Pod1 expression in EPDCs is activated by retinoic acid signaling. Pod1 knockout mouse model, immunofluorescence for smooth muscle markers, retinoic acid treatment of isolated chick EPDCs, in vivo RA inhibition experiments Developmental biology High 22687751
2013 Tcf21 is required for proepicardial cell specification and formation of a mature epithelial epicardium in Xenopus; mass spectrometry of Tcf21 immunoprecipitates established its association with transcriptional co-repressor proteins, supporting a function for Tcf21 as a transcriptional repressor that controls proepicardial lineage determination. Tcf21 depletion in Xenopus (morpholino), mass spectrometry-based interactome, in vivo systems analysis of gene expression changes Development (Cambridge, England) High 23637334
2014 The lncRNA TARID activates TCF21 expression by inducing promoter demethylation: TARID physically interacts with both the TCF21 promoter and GADD45A, which then recruits thymine-DNA glycosylase for base-excision-repair-mediated demethylation; this involves TET-enzyme-mediated oxidation of 5-methylcytosine to 5-hydroxymethylcytosine at the TCF21 promoter. RNA immunoprecipitation, chromatin immunoprecipitation, bisulfite sequencing, base-excision repair assays, TET enzyme inhibition Molecular cell High 25087872
2006 TCF21 is epigenetically silenced in lung and head and neck cancers by aberrant promoter methylation; exogenous expression of TCF21 in cells that have silenced endogenous TCF21 reduces tumor properties in vitro and in vivo, establishing a tumor suppressor function linked to its role in regulating mesenchymal-to-epithelial transition. Restriction landmark genomic scanning, methylation-specific PCR, exogenous TCF21 expression in cell lines, in vitro and xenograft tumor assays Proceedings of the National Academy of Sciences of the United States of America High 16415157
2014 A coronary heart disease–associated SNP (rs12190287) in the TCF21 3'-UTR disrupts an miR-224 binding site; the disease-associated C allele shows faster RNA–RNA complex formation and greater miR-224 binding compared with the protective G allele, leading to allele-specific reduction of TCF21 expression; miR-224 modulates TCF21 transcriptional response to TGF-β and PDGF signaling in an allele-specific manner. 3'-UTR reporter gene assays in HCASMC, kinetic in vitro RNA-RNA binding assays, Pb2+/RNase T1 RNA probing, allelic imbalance analysis, miR-224 modulation experiments PLoS genetics High 24676100
2013 The lead CHD-associated polymorphism rs12190287 disrupts an atypical AP-1 element in a TCF21 cis-regulatory enhancer, as demonstrated by allele-specific transcriptional regulation, transcription factor binding, and chromatin organization; this element also mediates signaling through PDGFR-β and WT1 pathways to regulate TCF21 expression. Luciferase reporter allele-specific assays, EMSA/TF binding assays, chromatin accessibility analysis, PDGFR-β and WT1 pathway perturbation experiments PLoS genetics High 23874238
2015 TCF21 promotes proliferation and migration and inhibits SMC lineage marker expression in human coronary artery SMC (HCASMC); vascular wall cells expressing Tcf21 migrate into atherosclerotic vascular lesions and contribute to the fibrous cap, where they activate SMC marker and growth factor receptor gene expression; RNA-Seq after siRNA knockdown identified downstream pathways related to vascular disease, cellular movement, and growth/proliferation. siRNA knockdown + RNA-Seq in HCASMC, in vitro proliferation/migration assays, reporter gene studies, immunolocalization, Cre-based lineage tracing in ApoE-/- and Ldlr-/- mice PLoS genetics High 26020946
2019 TCF21 antagonizes the MYOCD-SRF pathway to suppress SMC differentiation through multiple mechanisms: (1) TCF21 suppresses MYOCD and SRF at RNA and protein level; (2) ChIP-seq shows TCF21 binding colocalizes with SRF binding sites including at a novel SRF gene enhancer and MYOCD gene promoter; (3) TCF21 directly inhibits transcription at these sites via reporter assays; (4) TCF21 physically interacts with MYOCD (protein co-immunoprecipitation), blocking MYOCD-SRF association. ChIP-seq, siRNA/overexpression in HCASMC, luciferase reporter transfection assays, protein co-immunoprecipitation, in vitro genome editing of SRF CArG box, mouse in vivo mutation of orthologous enhancer Circulation research High 31815603
2019 SMC-specific knockout of TCF21 in mice markedly inhibits SMC phenotypic modulation in atherosclerosis, leading to fewer fibromyocytes and fewer fibrous cap cells within lesions; single-cell RNA-seq established that modulated SMCs transform into fibroblast-like 'fibromyocytes' (not macrophages), and TCF21 expression strongly associates with this process in human coronary arteries. SMC-specific TCF21 knockout mouse, single-cell RNA sequencing of mouse and human atherosclerotic lesions, immunohistochemistry Nature medicine High 31359001
2018 TCF21 and SMAD3 promote opposing transcriptional programs in HCASMC: SMAD3 promotes SMC differentiation marker expression while inhibiting proliferation, opposing TCF21's pro-dedifferentiation activity; at colocalized DNA binding sites, SMAD3 and TCF21 binding are inversely correlated, with TCF21 locally blocking chromatin accessibility at SMAD3 binding sites; TCF21 directly inhibits SMAD3 activation of gene expression in reporter assays. RNA-Seq, ChIP-Seq for SMAD3 and TCF21 in HCASMC, chromatin accessibility (ATAC-seq), luciferase reporter transfection assays, siRNA knockdown PLoS genetics High 30307970
2015 ChIP-seq in HCASMC identified the canonical TCF21 DNA binding sequence as CAGCTG; TCF21 binding sites significantly overlap AP-1 (JUN/JUND) binding loci in HCASMC; TCF21 target genes are enriched for processes including 'growth factor binding,' 'matrix interaction,' and 'smooth muscle contraction.' ChIP-seq with TCF21, JUN, and JUND antibodies in HCASMC; motif analysis; eQTL overlap analysis PLoS genetics High 26020271
2011 TCF21 binds the promoter of the melanoma metastasis-suppressing gene KISS1 and enhances its gene expression through interaction with E12 (TCF3 isoform) and TCF12; loss of TCF21 expression causes loss of KISS1 expression through loss of direct TCF21 occupancy at the KISS1 promoter; TCF21 overexpression inhibits motility of melanoma cells. Chromatin immunoprecipitation at KISS1 promoter, co-immunoprecipitation with E12/TCF12, siRNA knockdown, cell motility assays Carcinogenesis Medium 21771727
2011 SRY directly binds to the Tcf21 promoter at SRY/SOX9 response elements and activates TCF21 gene expression; mutagenesis of SRY/SOX9 response elements in the Tcf21 promoter eliminates SRY-driven activation; SRY was found to associate with the Tcf21 promoter in vivo during fetal rat testis development; TCF21 promotes in vitro sex reversal of embryonic ovarian cells to induce precursor Sertoli cell differentiation. Promoter reporter assays with mutagenesis, ChIP of SRY at Tcf21 promoter in fetal rat testis, embryonic ovarian cell culture sex-reversal assay, transcriptome analysis PloS one High 21637323
2012 ChIP-chip analysis identified 121 direct downstream TCF21 binding targets in Sertoli cells; one key bHLH target is scleraxis (Scx); SRY and TCF21 induce initial stages of Sertoli cell differentiation, while SCX induces later stages, establishing a cascade SRY→TCF21→SCX that promotes Sertoli cell fate. ChIP-chip comparative hybridization for TCF21 targets, embryonic ovarian gonadal cell culture sex-reversal assay with Sry, Tcf21, and Scx transfections, transferrin gene expression as Sertoli marker Biology of reproduction Medium 23034159
2016 TCF21 is sumoylated by SUMO1 at lysine residue K24; mutation of K24 to arginine completely abolishes sumoylation; sumoylation stabilizes TCF21 protein without affecting subcellular localization; sumoylation enhances TCF21 interaction with HDAC1/2 (without affecting TCF21-ERα interaction); sumoylated TCF21 shows enhanced recruitment of HDAC1/2 to the pS2 promoter and enhanced repression of ERα transcriptional activity; SENP1 reverses TCF21 sumoylation. Co-immunoprecipitation for SUMO1-TCF21 and HDAC1/2-TCF21, site-directed mutagenesis (K24R), protein half-life assay with SUMOylation inhibitor, subcellular localization assay, ChIP at pS2 promoter, luciferase reporter assay Oncotarget Medium 27028856
2019 TCF21 is required for visceral adipose stem cell (ASC)-specific expression of IL-6; TCF21 also promotes MMP-dependent collagen degradation and type IV collagen deposition through regulation of MMP2, MMP13, TIMP1, and COL4A1 in visceral ASCs; the MMP2 and COL4A1 regulatory effects are IL-6-independent. siRNA-mediated Tcf21 knockdown and lentiviral TCF21 overexpression in mouse ASCs, qRT-PCR, ELISA for IL-6, zymography for MMP activity, collagen assays The Journal of biological chemistry Medium 29540474
2015 POD-1/TCF21 overexpression reduces SHP mRNA and protein levels by binding to E-box sequences in the SHP promoter (demonstrated by ChIP), indirectly affecting LRH-1 regulation and increasing Cyclin E1 expression; this is mechanistically distinct from TCF21's regulation of SF-1. ChIP assay at SHP promoter, qRT-PCR, Western blot for SHP, LRH-1, and Cyclin E1 in hepatocarcinoma and adrenocortical tumor cells with POD-1 overexpression BioMed research international Medium 26421305
2015 POD-1/TCF21 overexpression significantly decreases endogenous SF-1 mRNA and protein in adrenal fasciculata/reticularis (F/R) cells, and also decreases the SF-1 target StAR; this effect is cell-zone-specific (not observed in glomerulosa cells), corroborating direct TCF21-mediated repression of SF-1 in normal adrenocortical cells. Primary culture of rat adrenal G and F/R cells, pCMVMycPod-1 transfection, qRT-PCR, Western blot for SF-1, StAR, CYP11B2 Brazilian journal of medical and biological research Medium 26421867
2019 TCF21 directly promotes LPL gene transcription by binding to the E-box motif in the LPL promoter, as demonstrated by ChIP and luciferase assays; TCF21 knockdown and overexpression attenuate and promote preadipocyte differentiation respectively, with changes in C/EBPα, LPL, and A-FABP expression. Chromatin immunoprecipitation assay, luciferase reporter assay, siRNA knockdown, TCF21 overexpression in chicken preadipocytes, lipid droplet accumulation quantification Frontiers in physiology Medium 31065241
2021 SUMOylation of TCF21 is increased in endometriotic tissues and is enhanced by estrogen; SUMOylation stabilizes TCF21 protein (shown by protein half-life assay with ginkgolic acid) and increases its interaction with USF2 (co-immunoprecipitation); SUMOylated TCF21 shows increased binding activity of USF2 to the SF-1 and ERβ promoters; TCF21/USF2 heterodimer binds to SF-1 and ERβ promoters to activate their expression. Co-immunoprecipitation, protein half-life assay with SUMOylation inhibitor, ChIP at SF-1 and ERβ promoters, estrogen treatment experiments in endometriotic stromal cells Biology of reproduction Medium 33693540
2022 ChIP-seq in adrenocortical carcinoma NCI-H295R cells overexpressing TCF21 identified CACNA1B (encoding N-type calcium channel Cav2.2) as a direct TCF21 target; TCF21 negatively regulates CACNA1B/Cav2.2 expression, suggesting a mechanism of steroidogenesis control in addition to SF-1 inhibition. ChIP-seq in NCI-H295R cells overexpressing TCF21, validation by qRT-PCR and Western blot for CACNA1B Neoplasma Medium 35603952
2025 Tcf21 directly binds gene loci including COL1A1, COL3A1, IL6, and PDGFRB (by ChIP-seq); Tcf21 promotes cardiac fibroblast activation and fibrosis through upregulation of extracellular matrix genes and the Pdgfrb-Erk pathway; Tcf21-knockout fibroblasts show severely suppressed Pdgfrb-Erk signaling; inducible Tcf21 KO mice are resistant to cardiac fibrosis induced by isoproterenol or metabolic overload. ChIP-seq in Tcf21-knockout vs WT cardiac fibroblasts, in vitro fibroblast culture from KO embryos, inducible Tcf21 KO mouse models (isoproterenol and streptozotocin/HFD), gene expression analysis Scientific reports High 40753125
2019 TCF21 inhibits anti-angiogenic activity in cholangiocarcinoma by targeting PI3K/Akt and ERK1/2 signaling; ectopic TCF21 expression in CCA cells reduces VEGFA and PDGF-BB expression/secretion (shown by immunohistochemistry and ELISA) and conditioned medium from TCF21-overexpressing cells reduces endothelial cell viability, migration, and tube formation; PI3K/Akt and ERK1/2 pathway inhibition mediates these effects. Lentiviral TCF21 overexpression in CCA cell lines, conditioned medium endothelial cell assays (viability, migration, tube formation), xenograft growth, immunohistochemistry, ELISA for VEGFA/PDGF-BB, Western blot for signaling pathway proteins American journal of physiology. Gastrointestinal and liver physiology Medium 30920845
2018 TCF21 interacts with p53 signaling as a transcriptional target of p53 in response to hypoxia in uterine endometrial carcinoma cells; TCF21 interferes with the MAPK pathway by reducing phosphorylated ERK1 (MAPK1), and a specific domain of TCF21 responsible for interaction with MEK was identified by molecular docking and mutagenesis. TCF21 overexpression in UCEC cells, hypoxia treatment of wild-type vs p53-deficient cells, molecular docking and mutagenesis of TCF21 domain, Western blot for phospho-ERK, in vitro proliferation and invasion assays, in vivo xenograft DNA and cell biology Low 29608330
2020 TCF21 overexpression in FAP-high cancer-associated fibroblasts (CAFs) in ovarian cancer decreases their ability to promote invasion, chemoresistance, and in vivo tumor growth, acting as a master regulator of CAF state; TCF21 is specifically expressed in FAP-low CAFs. TCF21 overexpression in FAP-high CAFs, co-culture invasion assays, in vivo tumor growth assays, flow cytometry for CD49e/FAP markers The Journal of experimental medicine Medium 32434219
2019 TCF21 lineage cells constitute the lung lipofibroblast population; after E15.5, Tcf21 progenitor cells exclusively become lipofibroblasts and interstitial fibroblasts; overexpression of Tcf21 in primary neonatal lung fibroblasts increases intracellular neutral lipids, suggesting Tcf21 regulates lipofibroblast function. Tcf21 inducible Cre lineage tracing at multiple embryonic time points, lipid staining (neutral lipid quantification), Tcf21 overexpression in neonatal lung fibroblasts American journal of physiology. Lung cellular and molecular physiology Medium 30675802
2023 DNMT3a binds the TCF21 promoter resulting in TCF21 hypermethylation in hepatic stellate cells (HSCs); TCF21 downstream binding protein hnRNPA1 inhibits the NF-κB signaling pathway to accelerate hepatic fibrosis reversal; the DNMT3a-TCF21-hnRNPA1 axis regulates HSC activation. ChIP for DNMT3a at TCF21 promoter, bisulfite sequencing, co-immunoprecipitation for TCF21-hnRNPA1 interaction, NF-κB pathway inhibition assays in HSCs Pharmacological research Medium 37268177
2023 TCF21 loss in epicardium-derived cells causes increased myofibroblast differentiation, whereas TCF21 overexpression suppresses TGF-β signaling and myofibroblast differentiation; lncRNA-TARID (enriched in mesenchymal stem cell EVs) upregulates Tcf21 expression in epicardium-derived cells, and TARID-laden lipid nanoparticles improve cardiac function in mouse and porcine myocardial infarction models. Gain- and loss-of-function experiments in epicardium-derived cells, TGF-β signaling pathway analysis (Western blot), intrapericardial EV injection in mouse MI model, lipid nanoparticle delivery of lncRNA-TARID in mouse and porcine MI models European heart journal Medium 36916305
2021 Tcf21 inhibits adipogenesis at least partially by accentuating Dlk1 expression; loss of Tcf21 in visceral adipose Tcf21 lineage cells (Tcf21 LCs) promotes adipogenesis and developmental progress, leading to improved metabolic health in diet-induced obesity; multiomics (scRNA-seq + chromatin accessibility) defined the gene-regulatory network governing Tcf21 LC activities. Tcf21 conditional knockout mice, scRNA-seq, ATAC-seq, gene-regulatory network analysis, metabolic phenotyping under HFD Cell reports Medium 36857185
2021 ChIP-seq in parietal epithelial cells (PECs) transfected with Tcf21-GFP identified a genome-wide Tcf21 binding site consensus as CAGCTG (E-box motif CANNTG); Tcf21 expression in PECs downregulates PEC-specific markers (caveolin-1, β-catenin, Pax2) and the transcription factor YY1; co-expression of YY1 with Tcf21 rescues Tcf21-induced multinucleation/budding/micronuclei and tetraploidy; Tcf21 target genes include cell cycle regulators (Mdm2, Cdc45, Cyclin D1, Cyclin D2) and microtubule stability genes. ChIP-seq in Tcf21-GFP-transfected PECs, motif analysis, qRT-PCR and Western blot for target genes/proteins, co-expression rescue experiments, flow cytometry for ploidy Cellular physiology and biochemistry Medium 34148307
2020 TCF21 directly interacts with HHIP protein (co-immunoprecipitation); inhibition of TCF21 or HHIP individually promotes liver cancer cell proliferation and metastasis; knockdown of TCF21 or HHIP counteracts the protective effects of miR-25-3p inhibitor on cell proliferation and metastasis. Co-immunoprecipitation for TCF21-HHIP interaction, luciferase reporter for miR-25-3p targeting, siRNA knockdown of TCF21/HHIP, CCK-8/transwell/wound-healing assays, xenograft Cell proliferation Low 32525231
2024 TCF21 directly binds the ABCA10 promoter (confirmed by dual-luciferase reporter and ChIP assay) to activate ABCA10 expression; TCF21 overexpression increases ABCA10-mediated mitochondrial cholesterol efflux in DDP-resistant ovarian cancer cells, sensitizing them to cisplatin; knockdown of ABCA10 reverses TCF21's ability to enhance cisplatin sensitivity. Dual-luciferase reporter assay, ChIP assay for TCF21 at ABCA10 promoter, lentiviral ABCA10 overexpression/knockdown and TCF21 overexpression in DDP-resistant OV cell lines, mitochondrial cholesterol measurement, cholesterol efflux assay, apoptosis assay Biochemical genetics Medium 39438390
2024 TCF21 directly activates PDE4C expression by binding to its promoter (confirmed by ChIP-seq and dual-luciferase reporter assay); TCF21 overexpression in endometrial stromal cells suppresses intracellular cAMP levels by upregulating PDE4C and also suppresses FOXO1 expression, thereby impairing decidualization. RNA-seq after TCF21 overexpression in HESCs, ChIP-seq and ChIP-qPCR for TCF21 at PDE4C promoter, dual-luciferase reporter assay, cAMP ELISA, FOXO1/decidual marker qRT-PCR/Western blot Biochimica et biophysica acta. Molecular basis of disease Medium 39326465
2025 TCF21 transcriptionally represses ERO1A expression (confirmed by dual-luciferase/ChIP assay); TCF21-mediated ERO1A repression reduces IDO1 expression and PD-L1 levels, thereby limiting immune evasion in lung adenocarcinoma cells; TCF21 overexpression inhibits LUAD cell migration/invasion and enhances CD8+ T cell cytotoxicity. Dual-luciferase assay and ChIP for TCF21-ERO1A binding, gene knockdown/overexpression experiments, Seahorse metabolic analysis, flow cytometry for CD8+ T cell activation, transwell migration/invasion assays, LUAD mouse models The international journal of biochemistry & cell biology Medium 40659157
2026 TCF21 directly activates LIMK2 transcription (ChIP-seq and epigenomic data in patient-derived ectopic stromal cells); TCF21-activated LIMK2-cofilin signaling promotes actin-cytoskeleton reorganization, increased cell invasion and adhesion in endometriotic stromal cells; uterine-specific Tcf21 knockout in mice dysregulates EMT of endometrium; TCF21 overexpression via AAV-Pgr-Tcf21 increases endometriosis incidence in mice, which is mitigated by LIMK inhibitor LIMKi 3. ChIP-seq in patient-derived ectopic stromal cells, uterine-specific Tcf21 conditional KO mice, AAV-Pgr-Tcf21 mouse model, LIMK inhibitor treatment, actin cytoskeleton imaging, invasion/adhesion assays Nature communications High 41786705
2021 TCF21 directly promotes chicken preadipocyte differentiation by binding to the E-box motif in the HTR2A promoter (genome-wide ChIP-seq, ChIP-qPCR, and luciferase reporter assay); pharmacological activation or inhibition of HTR2A respectively promotes or attenuates preadipocyte differentiation; HTR2A inhibition impairs TCF21-promoted adipogenesis. ChIP-seq and RNA-seq in chicken differentiated preadipocytes, ChIP-qPCR and luciferase reporter validation of HTR2A as direct target, pharmacological HTR2A modulation, oil red-O staining Biochemical and biophysical research communications Medium 34872001
2025 Loss of Tcf21 in cardiac fibroblasts causes increased myofibroblast-like gene expression and differentiation; AAV-mediated cardiac fibroblast-specific TCF21 overexpression in vivo exerts an anti-fibrotic effect and improves cardiac remodelling in a mouse model; snRNA-seq identified a disease-specific fibroblast subpopulation in human aortic stenosis where TCF21 is a key regulator. snRNA-seq of human fibrotic and non-failing hearts, cardiac fibroblast-specific AAV-knockdown and AAV-overexpression in vivo in mice, in vitro cardiac fibroblast loss/gain-of-function, immunohistochemistry Cardiovascular research High 41926244
2022 TCF21 in tumor pericytes increases perivascular ECM stiffness, collagen rearrangement, and basement membrane degradation; loss of integrin α5 in TCF21-high pericytes inhibits the FAK/PI3K/AKT/DNMT1 axis to impair TCF21 DNA hypermethylation; pericyte-conditional Tcf21 knockout mitigates perivascular ECM remodelling and colorectal cancer liver metastasis. scRNA-seq, pericyte-conditional Tcf21 KO mice (CRC model), ChIP-seq and bisulfite-seq, atomic force microscopy for ECM stiffness, second-harmonic generation microscopy, integrin α5 pathway inhibition studies Gut Medium 36805487
2017 TCF21 (Tcf21) directly regulates the Slug promoter by occupying E-box sequences; Tcf21-Slug balance defines distinct migratory modalities (proliferative/passive cooperative cell migration, active CCM, and EMT) in high-grade serous ovarian cancer cells; phenotypic transitions following drug exposure ensue from occupancy of Slug promoter E-boxes by Tcf21. ChIP at Slug promoter E-boxes, gene manipulation (overexpression/knockdown) of Tcf21 and Slug, live imaging of cell migration, flow cytometry Carcinogenesis Medium 31241128
2024 Tcf21 is required for specification of Foxd1+ stromal progenitors to the juxtaglomerular (JG) cell lineage during early kidney development (E12); Tcf21 inactivation in Foxd1+ cells (but not in Ren1+ cells) results in fewer renin-positive areas and altered renal arterial morphology; pseudotime trajectory analysis shows Tcf21 expression is highest in early metanephric mesenchyme and declines as cells mature into renin-expressing JG cells. Foxd1;Tcf21 conditional KO and Ren1;Tcf21 conditional KO mouse models, immunostaining, in situ hybridization, scRNA-seq, scATAC-seq, pseudotime trajectory analysis American journal of physiology. Renal physiology High 39589156
2024 Loss of Tcf21 in Foxd1+ stromal progenitors results in depletion of multiple stromal subpopulations (medullary/perivascular, collecting duct-associated, proliferating, and nephrogenic zone-associated stroma) and emergence of a novel Emcn-expressing stromal population with profibrotic transcriptional programs; Tcf21 loss leads to architectural disruption, interstitial fibrosis, and impaired renal function in adult mice. scRNA-seq on E14.5 Foxd1-lineage cells from Tcf21-cKO and control kidneys, scATAC-seq, immunostaining, bulk RNA-seq at E18.5, histological analysis at 2 months American journal of physiology. Renal physiology High 41632505
2025 Loss of tcf21 in zebrafish epicardial cells reduces the presence of dedifferentiated cardiomyocytes in the injury area and impairs heart regeneration, establishing that epicardial Tcf21 is required for cardiomyocyte dedifferentiation during cardiac regeneration. Conditional tcf21 flox allele with 4-OHT-inducible CreERT2 in adult zebrafish, ventricular resection heart injury model, quantification of dedifferentiated cardiomyocytes, histological assessment of regeneration Developmental biology Medium 41360282
2017 TCF21 regulates miR-224-mediated allelic imbalance at rs12190287 in HCASMC: higher TCF21 expression is anti-correlated with miR-224 levels, and miR-224 modulates TCF21 transcriptional response to TGF-β and PDGF in an allele-specific manner, indicating bimodal regulatory complexity at this CAD locus (previously also shown: rs12190287 disrupts AP-1 binding; see PMID 23874238). miR-224 and TCF21 expression correlation in HCASMC; miR-224 overexpression and inhibition experiments with TGF-β/PDGF treatment, allele-specific reporter assays PLoS genetics Medium 24676100

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single-cell analysis. Nature medicine 667 31359001
2012 The bHLH transcription factor Tcf21 is required for lineage-specific EMT of cardiac fibroblast progenitors. Development (Cambridge, England) 391 22573622
2011 tcf21+ epicardial cells adopt non-myocardial fates during zebrafish heart development and regeneration. Development (Cambridge, England) 246 21653610
2014 Long noncoding RNA TARID directs demethylation and activation of the tumor suppressor TCF21 via GADD45A. Molecular cell 235 25087872
2018 CircRNA hsa_circ_100395 regulates miR-1228/TCF21 pathway to inhibit lung cancer progression. Cell cycle (Georgetown, Tex.) 163 30176158
2011 Efficient inducible Cre-mediated recombination in Tcf21 cell lineages in the heart and kidney. Genesis (New York, N.Y. : 2000) 138 21432986
2006 Epigenetic regulation of the tumor suppressor gene TCF21 on 6q23-q24 in lung and head and neck cancer. Proceedings of the National Academy of Sciences of the United States of America 137 16415157
2012 Pod1/Tcf21 is regulated by retinoic acid signaling and inhibits differentiation of epicardium-derived cells into smooth muscle in the developing heart. Developmental biology 109 22687751
2014 Coronary heart disease-associated variation in TCF21 disrupts a miR-224 binding site and miRNA-mediated regulation. PLoS genetics 95 24676100
2011 TCF21 and PCDH17 methylation: An innovative panel of biomarkers for a simultaneous detection of urological cancers. Epigenetics 94 21847011
2015 Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells That Contribute to the Fibrous Cap. PLoS genetics 88 26020946
2019 Coronary Disease-Associated Gene TCF21 Inhibits Smooth Muscle Cell Differentiation by Blocking the Myocardin-Serum Response Factor Pathway. Circulation research 84 31815603
2013 Tcf21 regulates the specification and maturation of proepicardial cells. Development (Cambridge, England) 78 23637334
2020 Distinct fibroblast functional states drive clinical outcomes in ovarian cancer and are regulated by TCF21. The Journal of experimental medicine 69 32434219
2022 Novel TCF21high pericyte subpopulation promotes colorectal cancer metastasis by remodelling perivascular matrix. Gut 67 36805487
2019 The Tcf21 lineage constitutes the lung lipofibroblast population. American journal of physiology. Lung cellular and molecular physiology 62 30675802
2013 Disease-related growth factor and embryonic signaling pathways modulate an enhancer of TCF21 expression at the 6q23.2 coronary heart disease locus. PLoS genetics 62 23874238
2021 CircMEMO1 modulates the promoter methylation and expression of TCF21 to regulate hepatocellular carcinoma progression and sorafenib treatment sensitivity. Molecular cancer 60 33985545
2010 Methylation of the candidate biomarker TCF21 is very frequent across a spectrum of early-stage nonsmall cell lung cancers. Cancer 60 20945327
2023 Intrapericardial long non-coding RNA-Tcf21 antisense RNA inducing demethylation administration promotes cardiac repair. European heart journal 59 36916305
2011 Epigenetic deregulation of TCF21 inhibits metastasis suppressor KISS1 in metastatic melanoma. Carcinogenesis 59 21771727
2019 CXCL12 promotes atherosclerosis by downregulating ABCA1 expression via the CXCR4/GSK3β/β-cateninT120/TCF21 pathway. Journal of lipid research 52 31662443
2018 Coronary artery disease genes SMAD3 and TCF21 promote opposing interactive genetic programs that regulate smooth muscle cell differentiation and disease risk. PLoS genetics 52 30307970
2017 MicroRNA-205 promotes cell invasion by repressing TCF21 in human ovarian cancer. Journal of ovarian research 52 28476165
2012 miR-21 downregulated TCF21 to inhibit KISS1 in renal cancer. Urology 51 23206776
2016 Curcumin increases exosomal TCF21 thus suppressing exosome-induced lung cancer. Oncotarget 47 27894084
2021 TCF21+ mesenchymal cells contribute to testis somatic cell development, homeostasis, and regeneration in mice. Nature communications 43 34162856
2020 TCF21: a critical transcription factor in health and cancer. Journal of molecular medicine (Berlin, Germany) 42 32542449
2015 Characterization of TCF21 Downstream Target Regions Identifies a Transcriptional Network Linking Multiple Independent Coronary Artery Disease Loci. PLoS genetics 40 26020271
2015 TCF21 hypermethylation in genetically quiescent clear cell sarcoma of the kidney. Oncotarget 40 26158413
2008 Differential methylation of a short CpG-rich sequence within exon 1 of TCF21 gene: a promising cancer biomarker assay. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 36 18398044
2011 Basic helix-loop-helix transcription factor TCF21 is a downstream target of the male sex determining gene SRY. PloS one 34 21637323
2017 TCF21 functions as a tumor suppressor in colorectal cancer through inactivation of PI3K/AKT signaling. OncoTargets and therapy 30 28352192
2015 Down-regulation of TCF21 by hypermethylation induces cell proliferation, migration and invasion in colorectal cancer. Biochemical and biophysical research communications 30 26435499
2019 MicroRNA-3648 Is Upregulated to Suppress TCF21, Resulting in Promotion of Invasion and Metastasis of Human Bladder Cancer. Molecular therapy. Nucleic acids 29 31071528
2017 Promoter methylation of TCF21 may repress autophagy in the progression of lung cancer. Journal of cell communication and signaling 28 29086202
2012 SRY induced TCF21 genome-wide targets and cascade of bHLH factors during Sertoli cell differentiation and male sex determination in rats. Biology of reproduction 26 23034159
2018 Transcription factor 21 (TCF21) promotes proinflammatory interleukin 6 expression and extracellular matrix remodeling in visceral adipose stem cells. The Journal of biological chemistry 25 29540474
2017 Prokineticin receptor-1-dependent paracrine and autocrine pathways control cardiac tcf21+ fibroblast progenitor cell transformation into adipocytes and vascular cells. Scientific reports 25 29038558
2020 Molecular mechanisms of coronary disease revealed using quantitative trait loci for TCF21 binding, chromatin accessibility, and chromosomal looping. Genome biology 24 32513244
2018 LncRNA LINC00163 upregulation suppresses lung cancer development though transcriptionally increasing TCF21 expression. American journal of cancer research 24 30662806
2015 Clinicopathological significance and biological role of TCF21 mRNA in breast cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 24 26044559
2015 Regional differences in WT-1 and Tcf21 expression during ventricular development: implications for myocardial compaction. PloS one 24 26390289
2019 MicroRNA-30-3p Suppresses Inflammatory Factor-Induced Endothelial Cell Injury by Targeting TCF21. Mediators of inflammation 23 31354385
2020 Exosomes secreted by chronic hepatitis B patients with PNALT and liver inflammation grade ≥ A2 promoted the progression of liver cancer by transferring miR-25-3p to inhibit the co-expression of TCF21 and HHIP. Cell proliferation 22 32525231
2019 TCF21 inhibits tumor-associated angiogenesis and suppresses the growth of cholangiocarcinoma by targeting PI3K/Akt and ERK signaling. American journal of physiology. Gastrointestinal and liver physiology 19 30920845
2017 TCF21 hypermethylation regulates renal tumor cell clonogenic proliferation and migration. Molecular oncology 19 29080283
2020 Functional balance between Tcf21-Slug defines cellular plasticity and migratory modalities in high grade serous ovarian cancer cell lines. Carcinogenesis 18 31241128
2019 A Novel Regulator of Preadipocyte Differentiation, Transcription Factor TCF21, Functions Partially Through Promoting LPL Expression. Frontiers in physiology 18 31065241
2016 TCF21 genetic polymorphisms and breast cancer risk in Chinese women. Oncotarget 18 27270650
2012 A new Cre driver mouse line, Tcf21/Pod1-Cre, targets metanephric mesenchyme. PloS one 18 22792366
2017 TCF21 is related to testis growth and development in broiler chickens. Genetics, selection, evolution : GSE 17 28235410
2016 Sumoylation of TCF21 downregulates the transcriptional activity of estrogen receptor-alpha. Oncotarget 17 27028856
2017 Transcription Factor 21 (TCF21) rs12190287 Polymorphism is Associated with Osteosarcoma Risk and Outcomes in East Chinese Population. Medical science monitor : international medical journal of experimental and clinical research 16 28663539
2016 Clinical potential of TCF21 methylation in the diagnosis of renal cell carcinoma. Oncology letters 16 27446425
2023 Mechanism of TCF21 Downregulation Leading to Immunosuppression of Tumor-Associated Macrophages in Non-Small Cell Lung Cancer. Pharmaceutics 14 37765264
2018 A Novel Target of p53, TCF21, Can Respond to Hypoxia by MAPK Pathway Inactivation in Uterine Corpus Endometrial Carcinoma. DNA and cell biology 14 29608330
2018 Expression of Transcription Factor 21 (TCF21) and Upregulation Its Level Inhibits Invasion and Metastasis in Esophageal Squamous Cell Carcinoma. Medical science monitor : international medical journal of experimental and clinical research 14 29909422
2021 Role of the bHLH transcription factor TCF21 in development and tumorigenesis. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 12 33729392
2015 Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells that Contribute to the Fibrous Cap. Genomics data 11 26090325
2023 Tcf21 marks visceral adipose mesenchymal progenitors and functions as a rate-limiting factor during visceral adipose tissue development. Cell reports 10 36857185
2023 DNMT3a-mediated methylation of TCF21/hnRNPA1 aggravates hepatic fibrosis by regulating the NF-κB signaling pathway. Pharmacological research 10 37268177
2021 TCF21 regulates miR-10a-5p/LIN28B signaling to block the proliferation and invasion of melanoma cells. PloS one 10 34424910
2015 POD-1/TCF21 Reduces SHP Expression, Affecting LRH-1 Regulation and Cell Cycle Balance in Adrenocortical and Hepatocarcinoma Tumor Cells. BioMed research international 10 26421305
2018 TCF21 inhibits proliferation and chemoresistance through the AKT pathway in human gastric cancer. Gene 9 30296564
2022 Deficient or R273H and R248W Mutations of p53 Promote Chemoresistance to 5-FU via TCF21/CD44 Axis-Mediated Enhanced Stemness in Colorectal Carcinoma. Frontiers in cell and developmental biology 8 35071232
2019 Role of microRNA-92a in metastasis of osteosarcoma cells in vivo and in vitro by inhibiting expression of TCF21 with the transmission of bone marrow derived mesenchymal stem cells. Cancer cell international 8 30804710
2015 POD-1/Tcf21 overexpression reduces endogenous SF-1 and StAR expression in rat adrenal cells. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 8 26421867
2020 TCF21 Promotes Luminal-Like Differentiation and Suppresses Metastasis in Bladder Cancer. Molecular cancer research : MCR 7 32122956
2022 Association Between TCF21 Gene Polymorphism with the Incidence of Paroxysmal Atrial Fibrillation and the Efficacy of Radiofrequency Ablation for Patients with Paroxysmal Atrial Fibrillation. International journal of general medicine 6 35601004
2022 Delivery of miR-654-5p via SonoVue Microbubble Ultrasound Inhibits Proliferation, Migration, and Invasion of Vascular Smooth Muscle Cells and Arterial Thrombosis and Stenosis through Targeting TCF21. Oxidative medicine and cellular longevity 6 35910838
2021 Increased SUMOylation of TCF21 improves its stability and function in human endometriotic stromal cells†. Biology of reproduction 6 33693540
2021 Genome-wide survey and functional analysis reveal TCF21 promotes chicken preadipocyte differentiation by directly upregulating HTR2A. Biochemical and biophysical research communications 6 34872001
2023 Tcf21 Alleviates Pancreatic Fibrosis by Regulating the Epithelial-Mesenchymal Transformation of Pancreatic Stellate Cells. Digestive diseases and sciences 5 36943591
2019 Dysregulation of ß-catenin, WISP1 and TCF21 predicts disease-specific survival and primary response against radio(chemo)therapy in patients with locally advanced squamous cell carcinomas of the head and neck. Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery 5 30615266
2019 Promoter methylation of the candidate tumor suppressor gene TCF21 in myelodysplastic syndrome and acute myeloid leukemia. American journal of translational research 5 31312357
2024 Targeting Mitochondrial Cholesterol Efflux via TCF21/ABCA10 Pathway to Enhance Cisplatin Efficacy in Ovarian Cancer. Biochemical genetics 4 39438390
2020 lncRNA PICART1 alleviates progression of cervical cancer by upregulating TCF21. Oncology letters 4 32382324
2017 New evidences on the regulation of SF-1 expression by POD1/TCF21 in adrenocortical tumor cells. Clinics (Sao Paulo, Brazil) 4 28658440
2025 Tcf21 modulates fibroblast activation and promotes cardiac fibrosis after injury via Pdgfrb signaling. Scientific reports 3 40753125
2022 N-type calcium channel v2.2 is a target of TCF21 in adrenocortical carcinomas. Neoplasma 3 35603952
2021 Upregulation of TCF21 inhibits migration of adrenocortical carcinoma cells. Discover oncology 3 35201460
2019 [Effect of TCF21 on proliferation, migration and vascular production of breast cancer cells]. Zhonghua bing li xue za zhi = Chinese journal of pathology 3 30955268
2014 [Effects of tumor suppressor gene TCF21 on the proliferation, migration and apoptosis of A549 cells]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 3 24758904
2021 Studies on the Role of the Transcription Factor Tcf21 in the Transdifferentiation of Parietal Epithelial Cells into Podocyte-Like Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2 34148307
2026 miR-124 orchestrates epicardial-mesenchymal transformation and paracrine cardiomyocyte maturation in epicardial-specific Tcf21-PKR1 knockout mice. Stem cells (Dayton, Ohio) 1 41460181
2026 Single nucleus RNA sequencing and functional in vivo studies reveal TCF21 as a protective regulator in cardiac fibrosis. Cardiovascular research 1 41926244
2025 Inhibition of ERO1A by TCF21 curbs aerobic glycolysis and enhances immune recognition in lung adenocarcinoma. The international journal of biochemistry & cell biology 1 40659157
2024 TCF21 rs2327429 and TCF21 rs12190287 are associated with colorectal cancer in a Chinese population. Biomarkers in medicine 1 38197316
2024 Transcription factor Tcf21 modulates urinary bladder size and differentiation. Development, growth & differentiation 1 38197329
2024 The transcription factor TCF21 is necessary for adoption of cell fates by Foxd1+ stromal progenitors during kidney development. bioRxiv : the preprint server for biology 1 39211232
2024 Aberrant TCF21 upregulation in adenomyosis impairs endometrial decidualization by increasing PDE4C expression. Biochimica et biophysica acta. Molecular basis of disease 1 39326465
2024 Tcf21 as a founder transcription factor in specifying Foxd1 cells to the juxtaglomerular cell lineage. American journal of physiology. Renal physiology 1 39589156
2024 Down-regulated BNC1 promotes glioma by inhibiting ferroptosis via TCF21/PI3K signaling pathway BNC1TCF21PI3K. Tissue & cell 1 39603023
2026 The transcription factor Tcf21 is necessary for adoption of cell fates by Foxd1+ stromal progenitors during kidney development. American journal of physiology. Renal physiology 0 41632505
2026 TCF21-WNT5A axis drives metastasis of colorectal cancer via stromal-tumor cell communication. Journal of translational medicine 0 41673874
2026 TCF21 promotes epithelial-to-mesenchymal transition and cytoskeleton reorganization in uterine development and endometriosis. Nature communications 0 41786705
2025 TCF21 Downregulation Induces ERO1A Expression and Upregulates IDO1 to Trigger Immune Escape in Lung Adenocarcinoma. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 0 41290516
2025 Epicardial Tcf21 facilitates cardiomyocyte dedifferentiation and heart regeneration in zebrafish. Developmental biology 0 41360282
2024 Tcf21 as a Founder Transcription Factor in Specifying Foxd1 Cells to the Juxtaglomerular Cell Lineage. bioRxiv : the preprint server for biology 0 38585851

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