Affinage

TFAP2C

Transcription factor AP-2 gamma · UniProt Q92754

Length
450 aa
Mass
49.2 kDa
Annotated
2026-06-10
77 papers in source corpus 48 papers cited in narrative 47 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TFAP2C is a sequence-specific AP-2 family transcription factor that recognizes the SCCTSRGGS consensus element and directly activates or represses several hundred target genes to control lineage specification, pluripotency, and proliferative programs (PMID:20629094). In early development it functions as a master regulator of cell-fate decisions: in totipotent mouse embryos it acts as a 'bipotency activator' that binds and activates both inner-cell-mass and trophectoderm genes, then resolves fate by partitioning between CDX2- and SOX2-bound loci, cooperating with TEAD4 and Hippo signaling to establish a bistable lineage switch (PMID:38243114, PMID:38789684, PMID:40600821). It is required for primordial germ cell maintenance and, together with SOX17 and GATA factors, is sufficient to drive human PGC-like cell specification, in part through a TFAP2C-bound enhancer at the OCT4/POU5F1 locus (PMID:23967156, PMID:30590035, PMID:33608411); it also maintains naive human pluripotency by opening enhancers near pluripotency genes (PMID:29695788). In differentiating tissues TFAP2C initiates the surface-ectoderm chromatin landscape and induces p63 to launch the keratinocyte program (PMID:30686763), and it is essential for trophoblast proliferation and invasive trophoblast function during placentation, where loss causes growth restriction and lethality in a gene-dosage-dependent manner (PMID:26811378, PMID:39625795, PMID:39554130). As a transcriptional regulator it both activates targets and recruits corepressor machinery: it forms a ternary complex with Myc and the demethylase KDM5B to repress CDKN1A (p21) and drive S-phase entry (PMID:22371483), physically associates with the Sin3a-complex member Arid4b (PMID:33907498), and recruits HDAC1/2 to enhancers and promoters to deacetylate H3K27 and suppress transcription (PMID:38645262, PMID:41703284). In breast cancer it establishes and maintains luminal identity through direct regulation of ESR1/ERα, FOXA1, EGFR, RET, GPX1, and CA12, with binding at these targets gated by CpG methylation and histone deacetylation (PMID:17875680, PMID:19458056, PMID:20629094, PMID:22964634, PMID:22878616, PMID:26832794, PMID:31636386). Across diverse cancers TFAP2C activates oncogenic programs and confers therapy resistance, frequently by suppressing ferroptosis or activating PI3K/AKT, β-catenin, and NRF2 pathways through direct target activation (PMID:38243003, PMID:39536858, PMID:40541807, PMID:41703284, PMID:40667743).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2006 High

    Established that the AP-2 gamma factor binds and transactivates a defined enhancer in a trophoblast gene, providing the first direct biochemical evidence of its sequence-specific transcriptional activity.

    Evidence DNA-affinity purification, mass-spec identification, EMSA, ChIP and luciferase on the rat placental lactogen II enhancer in trophoblast cells

    PMID:16794002

    Open questions at the time
    • Single target gene; genome-wide binding repertoire undefined
    • Mammalian developmental requirement not yet tested
  2. 2006 High

    Demonstrated through genetic epistasis that tfap2c functions redundantly with tfap2a in neural crest induction, indicating an early ectodermal patterning role masked by paralog redundancy.

    Evidence Single and double antisense morpholino knockdown with transplant cell-autonomy tests in zebrafish embryos

    PMID:17258188

    Open questions at the time
    • Single knockdown shows no phenotype, leaving non-redundant functions unresolved
    • Direct target genes in neural crest not mapped
  3. 2007 High

    Identified TFAP2C as a direct activator of the ERα promoter that drives estrogen-dependent breast cancer growth, defining its role in hormone-responsive tumor biology.

    Evidence ChIP, siRNA knockdown, and xenograft assays in breast cancer cells

    PMID:17875680

    Open questions at the time
    • Did not address why binding is restricted to certain cell contexts
    • Broader target set unknown
  4. 2009 High

    Showed that TFAP2C promoter occupancy is epigenetically gated, explaining context-dependent target activation in ERα-positive versus negative tumors.

    Evidence ChIP, methylation analysis, chromatin accessibility assays, and AZA/TSA pharmacologic rescue in breast cancer cells

    PMID:19458056

    Open questions at the time
    • Mechanism linking methylation to loss of binding affinity not resolved structurally
    • Generality across other targets initially untested
  5. 2010 High

    Defined the genome-wide TFAP2C binding consensus and primary target set, converting it from a single-gene regulator to a network hub controlling estrogen and growth-factor signaling.

    Evidence ChIP-seq plus expression arrays after knockdown in MCF-7 cells

    PMID:20629094

    Open questions at the time
    • Direct versus indirect effects not fully separated for all 447 targets
    • Cofactor requirements for activation vs repression unaddressed
  6. 2012 High

    Revealed a repressive mechanism in which TFAP2C nucleates a ternary complex with Myc and KDM5B to silence p21 and drive cell-cycle progression, establishing it as a corepressor-recruiting factor as well as an activator.

    Evidence Reciprocal co-IP, endogenous ChIP, domain-mapping mutagenesis and cell-cycle readouts

    PMID:22371483

    Open questions at the time
    • Structural basis of the ternary complex unknown
    • Whether this complex operates at other loci untested
  7. 2012 High

    Expanded the direct target repertoire to GPX1 and the RET proto-oncogene, with GPX1 again gated by CpG methylation, reinforcing the epigenetically controlled, ER-independent regulatory program.

    Evidence ChIP-seq, EMSA, luciferase reporters, knockdown and 5-aza-dC rescue in breast cancer cells

    PMID:22878616 PMID:22964634

    Open questions at the time
    • Functional consequence of each target on tumor phenotype not fully dissected
  8. 2013 High

    Established TFAP2C as essential for primordial germ cell maintenance through direct regulation of germ-cell and DNA-methylation machinery genes, linking it to germline development and teratoma predisposition.

    Evidence Conditional knockout mouse, expression profiling, and ChIP at multiple germline target loci

    PMID:23967156

    Open questions at the time
    • Cofactors directing germline-specific binding not identified
    • Mechanism of teratoma predisposition incompletely defined
  9. 2014 High

    Showed TFAP2C maintains luminal breast epithelial identity, with loss driving EMT and a basal cell-state shift in vivo, defining its role in epithelial lineage fidelity.

    Evidence siRNA knockdown, conditional knockout mammary mouse model, and FACS of mammary populations

    PMID:24469049

    Open questions at the time
    • Direct targets enforcing luminal identity not enumerated here
    • Reversibility of the state shift untested
  10. 2016 High

    Defined TFAP2C-driven trophoblast and placental development via repression of Cdkn1a and Dusp6 to sustain ERK/AKT signaling, and a parallel role driving EGFR/RET dependency in luminal breast cancer.

    Evidence Conditional knockout, signaling Westerns, human trophoblast knockdown, ChIP-seq and dual-knockdown epistasis with xenografts

    PMID:26811378 PMID:26832794

    Open questions at the time
    • Whether placental and tumor programs share cofactors unknown
  11. 2018 High

    Established TFAP2C as a pioneer-like enhancer-opening factor for naive pluripotency and germ-cell identity, with a specific OCT4 enhancer required for hPGCLC specification.

    Evidence ATAC-seq, ChIP-seq, loss/gain-of-function in human ESCs, and CRISPR enhancer deletion

    PMID:29695788 PMID:30590035

    Open questions at the time
    • Whether TFAP2C acts as a true pioneer factor on nucleosomal DNA not directly shown
    • Recruited remodelers unidentified
  12. 2019 High

    Positioned TFAP2C as the initiating factor in a two-stage epidermal differentiation cascade, sufficient to launch surface-ectoderm fate and induce p63, and identified a non-developmental role in cell-collision guidance via RND3.

    Evidence ATAC-seq, ChIP-seq, RNA-seq and gain-of-function in human PSCs; live imaging and actomyosin assays for collision guidance

    PMID:30686763 PMID:31659294

    Open questions at the time
    • How TFAP2C primes chromatin ahead of p63 mechanistically unresolved
    • Direct vs indirect control of RND3 not fully separated
  13. 2021 High

    Placed TFAP2C within the germline specification hierarchy downstream of GATA factors and identified its physical association with the Sin3a corepressor component Arid4b, connecting its repressive activity to a defined corepressor complex.

    Evidence TF sufficiency and knockout epistasis for hPGCLC induction; endogenous co-IP and PLA for Arid4b interaction

    PMID:33608411 PMID:33907498

    Open questions at the time
    • Arid4b interaction confidence is Medium and functional link to repression inferred
    • Direct contacts within the Sin3a complex not mapped
  14. 2024 High

    Defined TFAP2C as a bipotency/bistability activator in totipotent embryos that paradoxically activates both ICM and TE specifiers and, with TEAD4 and Hippo signaling, resolves the first lineage decision.

    Evidence uliCUT&RUN-seq, embryo knockout, gain/loss-of-function and Hippo/apical-domain readouts; direct Sox2 promoter binding shown

    PMID:38243114 PMID:38574734 PMID:38789684 PMID:40600821

    Open questions at the time
    • How the same factor activates opposing fate programs at distinct loci mechanistically unclear
    • Cofactor switching between CDX2 and SOX2 partners not fully explained
  15. 2024 High

    Demonstrated TFAP2C is required cell-autonomously for invasive trophoblast function in hemochorial placentation in a strict gene-dosage manner, with biallelic loss prenatally lethal.

    Evidence CRISPR global editing and invasive-trophoblast-specific Cre-lox conditional knockout with histology and growth measurements in rat

    PMID:39554130 PMID:39625795

    Open questions at the time
    • Direct invasion-program targets not enumerated
    • Basis of dosage sensitivity unresolved
  16. 2024 Medium

    Identified an enhancer-suppressive mechanism in which TFAP2C recruits HDAC1 to chromatin to limit enhancer H3K27 acetylation, with SUMO machinery modulating its genome-wide occupancy.

    Evidence ChIP-seq under UBA2 and TFAP2C knockdown plus chromatin interactome proteomics (preprint)

    PMID:38645262

    Open questions at the time
    • Preprint status warrants caution
    • Mechanism by which UBA2/SUMO controls TFAP2C binding indirect and undefined
  17. 2025 Medium

    Extended the HDAC-recruitment model to direct promoter repression of KEAP1, linking TFAP2C to NRF2-dependent antioxidant defense and ferroptosis resistance, consolidating its role as a recurrent suppressor of ferroptosis across cancers.

    Evidence ChIP, luciferase, HDAC1/2 recruitment analysis, and ferroptosis/redox assays in ovarian cancer cells

    PMID:41703284

    Open questions at the time
    • Whether KEAP1 repression uses the same Sin3a/HDAC complex as enhancer suppression untested
    • Generality across the multiple reported ferroptosis-resistance targets not unified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single factor switches between activating and HDAC-mediated repressive outputs at different loci, and what cofactors and chromatin features dictate this choice, remains unresolved.
  • No structural model of TFAP2C cofactor complexes
  • Determinants directing activator vs repressor mode at a given target undefined
  • Pioneer activity on nucleosomal DNA not directly demonstrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 5 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005634 nucleus 4 GO:0000228 nuclear chromosome 3
Pathway
R-HSA-1266738 Developmental Biology 7 R-HSA-1474165 Reproduction 4 R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1640170 Cell Cycle 3
Partners
ARID4BCDX2HDAC1KDM5BKLF5MYCSOX17TEAD4
Complex memberships
Sin3a corepressor complex (via Arid4b)TFAP2C-Myc-KDM5B ternary complex

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 TFAP2C directly binds the ERα (ESR1) promoter to activate transcription and regulates multiple estrogen signaling pathways (ERα, GPR30, FoxM1) in breast cancer cells; knockdown of TFAP2C abrogates mitogenic response to estrogen and reduces hormone-responsive tumor growth in xenografts. Chromatin immunoprecipitation (ChIP), gene knockdown (siRNA), xenograft assays, expression analysis Cancer research High 17875680
2009 TFAP2C binding to the ERα promoter is blocked by CpG methylation and histone deacetylation; treatment with 5-aza-dC and trichostatin A restores chromatin accessibility, enabling TFAP2C and RNA Pol II binding and ERα re-expression in ERα-negative breast cancer cells. ChIP, DNA methylation analysis, chromatin accessibility assay, drug treatment (AZA/TSA) Clinical cancer research High 19458056
2010 Genome-wide ChIP-seq for TFAP2C in MCF-7 cells defined the consensus chromatin-binding sequence as SCCTSRGGS and identified 447 primary target genes including ESR1, FOXA1, GREB1, WWOX, MYC, RET, and members of the retinoic acid response pathway. ChIP-seq, expression microarray with TFAP2C knockdown Genes, chromosomes & cancer High 20629094
2012 TFAP2C forms a ternary complex with Myc and the H3K4me3 demethylase KDM5B at the CDKN1A (p21cip) proximal promoter; all three proteins collaborate to repress p21, requiring the AP-2 binding site at -111/-103 and KDM5B demethylase activity. The TFAP2C C-terminal 270 aa are required for Myc and KDM5B interaction. Overexpression forces S-phase entry and attenuates checkpoint activation. Co-immunoprecipitation, ChIP, luciferase reporter assay, siRNA knockdown, domain-mapping mutagenesis Molecular and cellular biology High 22371483
2012 TFAP2C directly regulates GPX1 expression by binding to an AP-2 regulatory region in the GPX1 promoter; CpG methylation of this region in certain breast cancer cell lines blocks TFAP2C binding and silences GPX1, which can be reversed by 5-aza-dC treatment. ChIP-seq, siRNA knockdown, luciferase reporter assay, methylation analysis, 5-aza-dC treatment Oncogene High 22964634
2012 TFAP2C directly regulates expression of the RET proto-oncogene through five AP-2 binding sites in the RET promoter (confirmed by ChIP-seq and gel-shift), independently of estrogen receptor expression. ChIP-seq, gel-shift (EMSA), siRNA knockdown, luciferase reporter assay Annals of surgical oncology High 22878616
2013 TFAP2C directly binds an AP-2 regulatory region in the ECM1 promoter (confirmed by ChIP-seq and EMSA) and regulates ECM1 expression in melanoma cells; knockdown or overexpression of TFAP2C correspondingly decreases or increases ECM1. ChIP-seq, EMSA (gel-shift), siRNA knockdown, adenoviral overexpression, luciferase reporter assay, 5' RACE PloS one Medium 24023917
2013 TFAP2C is required for murine fetal primordial germ cell (PGC) maintenance and directly binds regulatory regions of target genes including Sfrp1, Dmrt1, Nanos3, c-Kit, Cdk6, Cdkn1a, Fgf4, Klf4, Dnmt3b, and Dnmt3l (confirmed by ChIP); haploinsufficiency predisposes to teratomas on 129S2/Sv background. Global gene expression profiling (knockout mESCs and PGC-like cells), chromatin immunoprecipitation (ChIP), conditional knockout mouse model PloS one High 23967156
2014 Knockdown of TFAP2C in luminal breast carcinoma cells induces epithelial-mesenchymal transition (loss of luminal gene expression, gain of basal gene expression). Conditional knockout of Tcfap2c in mouse mammary epithelium (MMTV-Cre) reduces CD24hi/CD49fmid luminal cell population and increases CD24mid/CD49fhi basal cell population. siRNA knockdown, conditional knockout mouse model, FACS analysis of mammary cell populations, expression profiling Oncogene High 24469049
2016 TFAP2C promotes NSCLC cell cycle progression and tumorigenesis by transcriptionally inducing oncogenic miR-183 (which blocks AKAP12-mediated cyclin D1 inhibition) and simultaneously downregulating tumor-suppressive miR-33a (resulting in CDK6 activation); validated in xenograft mouse model. Overexpression/knockdown assays, microRNA expression analysis, xenograft mouse model, cell cycle analysis Oncogene Medium 27593936
2016 TFAP2C transcriptionally upregulates TGFBR1 in NSCLC cells, which activates PAK1 signaling to promote tumor cell proliferation, migration, and EMT; validated in xenograft model. Microarray analysis, overexpression/knockdown assays, xenograft model, expression analysis of patient tissue Experimental & molecular medicine Medium 27885255
2016 TFAP2C directly regulates EGFR expression in luminal breast cancer (ChIP-seq); co-knockdown of EGFR and TFAP2C target RET reduces proliferation more than either alone; vandetanib response depends on TFAP2C expression. ChIP-seq, siRNA knockdown, cell proliferation assays, xenograft assays Molecular cancer therapeutics High 26832794
2016 TFAP2C regulates trophoblast proliferation and placental development by repressing Cdkn1a (p21) and Dusp6 to maintain ERK1/2 and AKT activation; loss of TFAP2C in TPBPA+ progenitors causes junctional zone growth arrest and reduced glycogen synthesis. Conditional knockout (Cre-lox), Western blot analysis of signaling pathways, gene expression analysis, knockdown in human trophoblast cell line (JAr) Development (Cambridge, England) High 26811378
2018 TFAP2C is upregulated during primed-to-naive pluripotency reversion, binds naive-specific enhancers genome-wide, facilitates opening of enhancers proximal to pluripotency factors (including a naive-specific OCT4/POU5F1 enhancer), and is required to maintain naive pluripotency and repress neuroectodermal differentiation. ATAC-seq, ChIP-seq, loss-of-function (siRNA/shRNA), gain-of-function in human ESCs, reporter assays Nature cell biology High 29695788
2018 TFAP2C-bound naive enhancer at the OCT4 (POU5F1) locus is required for OCT4 expression and hPGCLC identity; CRISPR/Cas9 deletion of this enhancer impairs OCT4 expression and hPGCLC specification. ATAC-seq, CRISPR/Cas9 enhancer deletion, expression analysis in hPGCs and hPGCLCs Cell reports High 30590035
2018 TFAP2C promotes colorectal cancer stemness and chemoresistance to 5-FU by inhibiting Hippo signaling via transcriptional upregulation of ROCK1 and ROCK2. Western blot, luciferase reporter assay, ChIP, in vitro and in vivo functional assays Journal of experimental & clinical cancer research Medium 29439714
2019 TFAP2C acts as the first transcription factor in a two-stage chromatin-remodeling cascade during epidermal differentiation: TFAP2C initiates surface ectoderm chromatin landscape and induces p63 expression and binding sites, enabling p63 to then autoregulate and mature the keratinocyte program. TFAP2C alone (not p63) is sufficient to initiate surface ectoderm differentiation. ATAC-seq, ChIP-seq, RNA-seq, overexpression of TFAP2C in human PSCs, inference regulatory network analysis, functional keratinocyte differentiation assays Cell stem cell High 30686763
2019 TFAP2C regulates cell collision guidance (reorientation of fibroblasts upon collision) in part by controlling expression of RND3; RND3 localizes to cell-cell collision zones and downregulates actomyosin activity there, enabling anisotropic extracellular matrix generation. Loss of TFAP2C leads to failure of cell collision guidance and isotropic matrix. Transcription factor knockdown/overexpression, live cell imaging, Vicsek modeling, RND3 localization experiments, actomyosin activity assays Nature materials High 31659294
2019 TFAP2C directly regulates CA12 (carbonic anhydrase XII) expression in luminal breast cancer by binding its promoter region (ChIP-seq), and also indirectly through upregulation of ERα; CA12 is epigenetically silenced in basal breast cancer by histone deacetylation and CpG methylation. ChIP-seq, siRNA knockdown, methylation analysis, TSA/5-aza-dC treatment, expression analysis in primary tumors Oncogene Medium 31636386
2019 TFAP2C increases NSCLC cell proliferation by downregulating GADD45B and PMAIP1 at both mRNA and protein levels, promoting cell cycle progression and motility. Microarray analysis, overexpression/knockdown, cell proliferation and motility assays Biological research Low 31296259
2020 TFAP2C promotes mesenchymal-to-epithelial transition (MET) during somatic cell reprogramming by directly binding epithelial gene promoters (ChIP-qPCR) to activate their expression; knockdown of E-cadherin (Cdh1), a direct TFAP2C target, antagonizes TFAP2C-mediated reprogramming. TFAP2C also inhibits c-Myc-dependent apoptosis during reprogramming. RNA-seq, ChIP-qPCR, overexpression/knockdown during iPSC reprogramming, siRNA knockdown of downstream targets Cell death & disease Medium 32587258
2020 METTL3 m6A-methylates TFAP2C mRNA, and this modification is read by IGF2BP1; this enhances TFAP2C mRNA stability and promotes seminoma cell survival under cisplatin treatment by upregulating DNA repair-related genes. m6A sequencing, RNA immunoprecipitation (RIP), expression analysis, knockdown/overexpression Journal of cellular and molecular medicine Medium 32857912
2020 TFAP2C suppresses miR-23a-5p expression by directly binding the miR-23a promoter (ChIP assay); miR-23a-5p targets SFRP5, an inhibitor of Wnt5a; through this axis, TFAP2C inhibits autophagy to reduce cardiomyocyte H/R injury. ChIP assay, dual-luciferase reporter assay, RIP assay, overexpression/knockdown, cell viability assays FASEB journal Medium 37191968
2021 GATA3 or GATA2 combined with SOX17 and TFAP2C are sufficient to generate human PGCLCs from pluripotent cells; SOX17, TFAP2C, and BLIMP1 alone are insufficient. GATA3/GATA2 knockouts dose-dependently impair BMP-induced hPGCLC specification, while GATA3/GATA2 expression is unaffected by SOX17, TFAP2C, or BLIMP1 knockouts—placing GATA3/GATA2 upstream of or parallel to SOX17/TFAP2C in BMP signaling. Transcription factor overexpression in human PSCs, gene knockout (siRNA/shRNA), hPGCLC induction assays, xenogeneic ovary reconstitution Life science alliance High 33608411
2021 TFAP2C physically interacts with Arid4b (a Sin3a corepressor complex member) in mouse ESCs, identified by endogenous co-immunoprecipitation and proximity ligation assay; this interaction is linked to repression of a subset of Tfap2c-regulated genes during meso/endoderm differentiation. Co-immunoprecipitation (endogenous), proximity ligation assay (PLA), ChIP (H3K27Ac), differentiation assays Turkish journal of biology Medium 33907498
2022 TFAP2C transcriptionally activates PCAT1 lncRNA expression in prostate cancer cells; PCAT1 then inhibits ferroptosis through c-Myc/miR-25-3p/SLC7A11 signaling to promote docetaxel resistance. ChIP assay, luciferase reporter assay, RNA sequencing, overexpression/knockdown, ferroptosis assays Frontiers in oncology Medium 35402284
2023 TFAP2C targets the pri-miRNA-132 gene in dorsal root ganglion neurons and represses miR-132-5p expression; exosomal TFAP2C (from fibroblasts) is transferred into axons where it promotes axon regeneration via the miR-132-5p/CAMKK1 axis. ChIP assay (TFAP2C binding to pri-miRNA-132), exosome isolation and proteomic identification, miRNA expression analysis, axon regeneration assays in vitro and in vivo (rat sciatic nerve model) Bioactive materials Medium 36936807
2024 In totipotent mouse embryos, TFAP2C acts as a 'bipotency activator' by binding and activating both early TE and ICM lineage genes at the 2–8-cell stages; upon trophoblast commitment, TFAP2C leaves ICM gene loci and co-occupies late TE genes with CDX2, then extra-embryonic ectoderm genes with SOX2. Tfap2c deficiency downregulates both early ICM genes (Nanog, Nr5a2, Tdgf1) and early TE genes (Tfeb, Itgb5), and increases ICM apoptosis. uliCUT&RUN-seq (in vivo TF binding), embryo Tfap2c knockout, expression analysis at multiple developmental stages Nature structural & molecular biology High 38243114
2024 TFAP2C and TEAD4 together accelerate loss of totipotency and promote lineage diversification by establishing a bistable switch; they paradoxically activate both TE specifiers and ICM specifiers in bipotent cells, with asymmetric apical domain segregation resolving this into Hippo-OFF (TE) or Hippo-ON (ICM) fates. TFAP2C activates specifiers of both ICM and TE fate. Overexpression and loss-of-function of TFAP2C and TEAD4 in mouse embryos, Hippo signaling readouts, live imaging of apical domain, lineage marker analysis Nature structural & molecular biology High 38789684
2024 TFAP2C binds to the Sox2 proximal promoter in mouse preimplantation embryos to activate Sox2 transcription; TFAP2C and Hippo signaling cooperatively regulate Sox2 expression. ChIP/CUT&RUN in embryos, loss-of-function via TFAP2C knockdown/knockout, cis-regulatory element deletion, Sox2 expression analysis Development (Cambridge, England) Medium 40600821
2024 TFAP2C defines a regulatory network in murine peri-implantation embryos involving TEAD4 and KLF5; maternal retinoic acid metabolism regulates TFAP2C expression and function via active demethylation of SINEs (RARG-TFAP2C-TEAD4/KLF5 axis); both genomic imprinting and SNPs influence TF positioning through TFAP2C. uliCUT&RUN-seq (genome-wide TF binding), TFAP2C loss-of-function, retinoic acid pathway manipulation, promoter-enhancer interaction analysis Developmental cell Medium 38574734
2024 TFAP2C transcriptionally activates CST1 (cystatin SN) expression by binding its promoter (dual-luciferase and ChIP assay); TFAP2C/CST1 axis promotes breast cancer cell proliferation and suppresses ferroptosis (GPX4-dependent). Dual-luciferase reporter assay, ChIP, siRNA knockdown, overexpression, cell cycle/apoptosis/ferroptosis assays, xenograft model Biochemical genetics Medium 38243003
2024 TFAP2C transcriptionally activates DDR1 in palbociclib-resistant breast cancer cells; inhibition of TFAP2C re-sensitizes resistant cells to palbociclib. TFAP2C-DDR1 gene signatures are enriched in patients after palbociclib treatment. Quantitative high-throughput combination screening, genomics/proteomics, siRNA knockdown, xenograft model, GSEA of clinical data Cancer letters Medium 39603379
2024 TFAP2C transcriptionally activates FLT3 expression (confirmed by dual-luciferase and ChIP); the TFAP2C/FLT3 axis inhibits ferroptosis in breast cancer by suppressing mitochondrial autophagy. Dual-luciferase reporter assay, ChIP, knockdown/overexpression, autophagy and ferroptosis assays The international journal of biochemistry & cell biology Medium 39536858
2024 TFAP2C directly binds the YAP promoter to activate its transcription (dual-luciferase and ChIP); TFAP2C promotes cisplatin resistance in bladder cancer through YAP upregulation and downstream β-catenin pathway activation. Dual-luciferase reporter assay, ChIP, siRNA knockdown, xenograft model The Journal of biological chemistry Medium 40541807
2024 Knockdown of UBA2 (SUMO activating enzyme) increases TFAP2C binding to enhancers genome-wide (not due to TFAP2C SUMOylation itself); TFAP2C recruits HDAC1 to chromatin, and TFAP2C knockdown reduces HDAC1 binding and increases H3K27Ac at enhancers, indicating TFAP2C is required for HDAC machinery recruitment to suppress enhancer activity. ChIP-seq (UBA2 KD and TFAP2C KD), proteomics of TFAP2C interactome on chromatin, molecular biology (ChIP for HDAC1), SUMOylation inhibitor Research square (preprint)preprint Medium 38645262
2024 TFAP2C is required for invasive trophoblast cell-specific functions in rat hemochorial placentation; conditional (Cre-lox) invasive trophoblast-specific disruption of Tfap2c inhibits intrauterine trophoblast invasion and causes intrauterine and postnatal growth restriction. Homozygous global disruption is prenatally lethal. Monoallelic conditional disruption does not impair invasion, indicating gene dosage dependence. CRISPR/Cas9 global genome editing, Cre-lox conditional mutagenesis, histological analysis of placentation site, growth measurements JCI insight High 39554130 39625795
2024 TFAP2C directly binds the STEAP3 promoter and positively regulates its expression (ChIP and luciferase); TFAP2C/STEAP3 axis activates β-catenin signaling to promote lung squamous cell carcinoma progression. ChIP assay, luciferase reporter assay, siRNA knockdown, overexpression, in vivo xenograft model Biology direct Medium 39716275
2025 TFAP2C binds to the KEAP1 promoter and recruits HDAC1/2, leading to H3K27 deacetylation and transcriptional repression of KEAP1; reduced KEAP1 stabilizes NRF2 protein, activating NRF2-dependent antioxidant transcription and conferring ferroptosis resistance in ovarian cancer. ChIP assay, dual-luciferase reporter assay, knockdown/overexpression, ROS/Fe2+/lipid peroxidation assays, mitochondrial membrane potential assay, rescue experiments Oncogene Medium 41703284
2025 E2F1 activates TFAP2C transcription by binding to its promoter, and the resulting E2F1-TFAP2C-SOX17 positive-feedback loop controls human germline stem cell fate (hPGCLC identity) in organoids from Turner syndrome iPSCs; E2F1 knockout impairs hPGCLC specification. Single-cell transcriptomics, organoid differentiation system, ChIP (E2F1 binding to TFAP2C promoter), E2F1 knockout, expression analysis Cell & bioscience Medium 41035077
2025 TFAP2C deletion is synthetic viable with HNRNPK depletion in glioma cells; HNRNPK depletion inhibits mTORC1 and increases prion propagation; TFAP2C overexpression enhances mTORC1 downstream functions. Co-deletion of TFAP2C with HNRNPK restores mTORC1 activity and reverses prion elevation, establishing epistatic interaction between TFAP2C, HNRNPK, and mTORC1 in metabolic and prion regulation. Synthetic-viability CRISPR screen, mTOR signaling assays, metabolic assays (ATP, autophagy), prion propagation assays, genetic epistasis PLoS pathogens Medium 42008486
2025 TFAP2C directly binds the TFAP2C promoter region and activates TFAP2C transcription in response to PART1/miR-302a-3p signaling; TFAP2C directly binds the DUSP5 promoter to activate DUSP5 expression, thereby suppressing autophagy and apoptosis in H/R-injured cardiomyocytes. Dual-luciferase reporter assay, ChIP assay, siRNA knockdown, flow cytometry, TUNEL, MIRI mouse model Korean circulation journal Medium 38654453
2025 TFAP2C directly binds to the PI3K promoter and activates its transcription (confirmed by ChIP and luciferase); through this mechanism TFAP2C activates the PI3K/AKT/mTOR pathway to promote EMT and proliferation in glioblastoma. ChIP assay, dual-luciferase reporter assay, siRNA knockdown, co-overexpression rescue, xenograft model Cell biology international Medium 40667743
2026 TFAP2C directly binds the VEGFA promoter to transcriptionally activate VEGFA expression in endothelial cells, facilitating VEGFA/VEGFR2-dependent angiogenesis; propofol suppresses this by activating ER stress (PERK/eIF2α phosphorylation) to reduce TFAP2C translation. ChIP assay, luciferase reporter assay, propofol treatment with ER stress pathway analysis, in vitro angiogenesis assays, in vivo angiogenesis model Apoptosis Medium 41524974
2006 In zebrafish, tfap2c (encoding AP-2 gamma) is expressed transiently in neural crest and non-neural ectoderm; simultaneous morpholino-knockdown of tfap2a and tfap2c completely prevents neural crest induction (epistasis showing redundancy), and reduces cranial placode derivatives. Single tfap2c knockdown alone shows no visible developmental defect. Antisense morpholino knockdown (single and double), transplant studies (cell autonomy), in situ hybridization, neural crest marker analysis in zebrafish embryos Developmental biology High 17258188
2006 AP-2 gamma (TFAP2C ortholog) binds a specific enhancer element (FP2 DNase I-protected region) in the rat placental lactogen II (rPLII) gene 5' flanking region in trophoblast cells; this binding was confirmed by gel-shift assay with AP-2 gamma-specific antiserum and chromatin immunoprecipitation in Rcho giant cells; AP-2 gamma transactivates the enhancer in cotransfection assays. Protein purification by DNA affinity, HPLC-MALDI-TOF mass spectrometry identification, gel-shift assay (EMSA), ChIP, cotransfection luciferase assay Endocrinology High 16794002
2025 TFAP2C directly binds the TFAP2C (proximal) promoter region and activates PTGES transcription in lung adenocarcinoma cells (confirmed by ChIP and dual-luciferase); PTGES promotes gefitinib resistance through NOTCH3 signaling, and TFAP2C knockdown-mediated loss of PTGES is reversed by PTGES overexpression. ChIP assay, dual-luciferase reporter assay, GSEA, knockdown/overexpression in PC-9/GR cells, NOTCH3 inhibitor rescue Journal of clinical biochemistry and nutrition Medium 40777819

Source papers

Stage 0 corpus · 77 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 microRNA-214 contributes to melanoma tumour progression through suppression of TFAP2C. The EMBO journal 216 21468029
2018 TFAP2C regulates transcription in human naive pluripotency by opening enhancers. Nature cell biology 147 29695788
2006 Redundant activities of Tfap2a and Tfap2c are required for neural crest induction and development of other non-neural ectoderm derivatives in zebrafish embryos. Developmental biology 121 17258188
2018 TFAP2C promotes stemness and chemotherapeutic resistance in colorectal cancer via inactivating hippo signaling pathway. Journal of experimental & clinical cancer research : CR 90 29439714
2022 TFAP2C-Mediated lncRNA PCAT1 Inhibits Ferroptosis in Docetaxel-Resistant Prostate Cancer Through c-Myc/miR-25-3p/SLC7A11 Signaling. Frontiers in oncology 89 35402284
2019 TFAP2C- and p63-Dependent Networks Sequentially Rearrange Chromatin Landscapes to Drive Human Epidermal Lineage Commitment. Cell stem cell 85 30686763
2019 Extracellular matrix anisotropy is determined by TFAP2C-dependent regulation of cell collisions. Nature materials 84 31659294
2007 TFAP2C controls hormone response in breast cancer cells through multiple pathways of estrogen signaling. Cancer research 71 17875680
2010 Identification of primary gene targets of TFAP2C in hormone responsive breast carcinoma cells. Genes, chromosomes & cancer 70 20629094
2018 The TFAP2C-Regulated OCT4 Naive Enhancer Is Involved in Human Germline Formation. Cell reports 68 30590035
2012 Histone demethylase KDM5B collaborates with TFAP2C and Myc to repress the cell cycle inhibitor p21(cip) (CDKN1A). Molecular and cellular biology 68 22371483
2018 MiR-10a-5p targets TFAP2C to promote gemcitabine resistance in pancreatic ductal adenocarcinoma. Journal of experimental & clinical cancer research : CR 62 29615098
2012 The role of transcription factor Tcfap2c/TFAP2C in trophectoderm development. Reproductive biomedicine online 62 22560121
2014 TFAP2C governs the luminal epithelial phenotype in mammary development and carcinogenesis. Oncogene 60 24469049
2019 TFAP2C-Activated MALAT1 Modulates the Chemoresistance of Docetaxel-Resistant Lung Adenocarcinoma Cells. Molecular therapy. Nucleic acids 57 30771618
2020 METTL3 potentiates resistance to cisplatin through m6 A modification of TFAP2C in seminoma. Journal of cellular and molecular medicine 56 32857912
2016 TFAP2C promotes lung tumorigenesis and aggressiveness through miR-183- and miR-33a-mediated cell cycle regulation. Oncogene 55 27593936
2009 Overexpression of TFAP2C in invasive breast cancer correlates with a poorer response to anti-hormone therapy and reduced patient survival. The Journal of pathology 53 18825690
2016 TFAP2C-mediated upregulation of TGFBR1 promotes lung tumorigenesis and epithelial-mesenchymal transition. Experimental & molecular medicine 52 27885255
2021 GATA transcription factors, SOX17 and TFAP2C, drive the human germ-cell specification program. Life science alliance 51 33608411
2017 Upregulation of microRNA-137 expression by Slug promotes tumor invasion and metastasis of non-small cell lung cancer cells through suppression of TFAP2C. Cancer letters 51 28610956
2015 A discrete transition zone organizes the topological and regulatory autonomy of the adjacent tfap2c and bmp7 genes. PLoS genetics 49 25569170
2012 Transcriptional regulation of the GPX1 gene by TFAP2C and aberrant CpG methylation in human breast cancer. Oncogene 48 22964634
2019 TFAP2C increases cell proliferation by downregulating GADD45B and PMAIP1 in non-small cell lung cancer cells. Biological research 47 31296259
2013 Transcription factor TFAP2C regulates major programs required for murine fetal germ cell maintenance and haploinsufficiency predisposes to teratomas in male mice. PloS one 41 23967156
2020 TFAP2C facilitates somatic cell reprogramming by inhibiting c-Myc-dependent apoptosis and promoting mesenchymal-to-epithelial transition. Cell death & disease 36 32587258
2024 Lineage regulators TFAP2C and NR5A2 function as bipotency activators in totipotent embryos. Nature structural & molecular biology 35 38243114
2009 Interaction of TFAP2C with the estrogen receptor-alpha promoter is controlled by chromatin structure. Clinical cancer research : an official journal of the American Association for Cancer Research 34 19458056
2016 EGFR Is Regulated by TFAP2C in Luminal Breast Cancer and Is a Target for Vandetanib. Molecular cancer therapeutics 33 26832794
2020 TFAP2C-mediated LINC00922 signaling underpins doxorubicin-resistant osteosarcoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 32 32563982
2016 Tpbpa-Cre-mediated deletion of TFAP2C leads to deregulation of Cdkn1a, Akt1 and the ERK pathway, causing placental growth arrest. Development (Cambridge, England) 31 26811378
2023 Fibroblast exosomal TFAP2C induced by chitosan oligosaccharides promotes peripheral axon regeneration via the miR-132-5p/CAMKK1 axis. Bioactive materials 26 36936807
2019 TFAP2C regulates carbonic anhydrase XII in human breast cancer. Oncogene 26 31636386
2012 Expression of the RET proto-oncogene is regulated by TFAP2C in breast cancer independent of the estrogen receptor. Annals of surgical oncology 24 22878616
2015 Reduced Gene Dosage of Tfap2c Impairs Trophoblast Lineage Differentiation and Alters Maternal Blood Spaces in the Mouse Placenta. Biology of reproduction 22 26063869
2011 The role of BLIMP1 and its putative downstream target TFAP2C in germ cell development and germ cell tumours. International journal of andrology 21 21564135
2022 TFAP2C Knockdown Sensitizes Bladder Cancer Cells to Cisplatin Treatment via Regulation of EGFR and NF-κB. Cancers 20 36230734
2013 Human Melanoma cells over-express extracellular matrix 1 (ECM1) which is regulated by TFAP2C. PloS one 20 24023917
2006 Proteomic identification of AP2 gamma as a rat placental lactogen II trophoblast cell-specific enhancer binding protein. Endocrinology 18 16794002
2019 A TFAP2C Gene Signature Is Predictive of Outcome in HER2-Positive Breast Cancer. Molecular cancer research : MCR 17 31619506
2024 Tead4 and Tfap2c generate bipotency and a bistable switch in totipotent embryos to promote robust lineage diversification. Nature structural & molecular biology 16 38789684
2021 Anlotinib inhibits the proliferation, migration and invasion, and induces apoptosis of breast cancer cells by downregulating TFAP2C. Oncology letters 15 34976158
2024 Defining a TFAP2C-centered transcription factor network during murine peri-implantation. Developmental cell 14 38574734
2024 TFAP2C Activates CST1 Transcription to Facilitate Breast Cancer Progression and Suppress Ferroptosis. Biochemical genetics 12 38243003
2023 KLF14/miR-1283/TFAP2C axis inhibits HER2-positive breast cancer progression via declining tumor cell proliferation. Molecular carcinogenesis 10 36752341
2022 Oncogenic LINC00857 recruits TFAP2C to elevate FAT1 expression in gastric cancer. Cancer science 10 35524544
2021 Fragile Gene WWOX Guides TFAP2A/TFAP2C-Dependent Actions Against Tumor Progression in Grade II Bladder Cancer. Frontiers in oncology 10 33718178
2010 Loss of transcription factor AP-2gamma/TFAP2C impairs branching morphogenesis of the murine mammary gland. Developmental dynamics : an official publication of the American Association of Anatomists 10 20131354
2020 MiR-29b-3p cooperates with miR-29c-3p to affect the malignant biological behaviors in T-cell acute lymphoblastic leukemia via TFAP2C/GPX1 axis. Biochemical and biophysical research communications 9 32423796
2024 TFAP2C/FLT3 axis reduces ferroptosis in breast cancer cells by inhibiting mitochondrial autophagy. The international journal of biochemistry & cell biology 8 39536858
2023 TFAP2C inhibits cell autophagy to alleviate myocardial ischemia/reperfusion injury by regulating miR-23a-5p/SFRP5/Wnt5a axis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 8 37191968
2020 CRISPR-on for activation of endogenous SMARCA4 and TFAP2C expression in bovine embryos. Reproduction (Cambridge, England) 8 32240977
2013 High TFAP2C/low CD44 expression is associated with an increased rate of pathologic complete response following neoadjuvant chemotherapy in breast cancer. The Journal of surgical research 8 23764310
2023 TFAP2C exacerbates psoriasis-like inflammation by promoting Th17 and Th1 cells activation through regulating TEAD4 transcription. Allergologia et immunopathologia 7 37169570
2020 LncRNA RP11-84E24.3 drives tumorigenesis and epithelial-to-mesenchymal transition of glioma cells by promoting TFAP2C-mediated activation of SNAI1. Journal of neuro-oncology 7 33128099
2025 Combining decitabine with radiotherapy to enhance nasopharyngeal carcinoma radiosensitivity via the TFAP2C-OTUD1-SLC25A11 axis. Cell death & disease 4 40664662
2024 LncRNA PART1 Attenuates Myocardial Ischemia-Reperfusion Injury by Regulating TFAP2C/DUSP5 Axis via miR-302a-3p. Korean circulation journal 4 38654453
2021 Arid4b physically interacts with Tfap2c in mouse embryonic stem cells. Turkish journal of biology = Turk biyoloji dergisi 4 33907498
2021 Corrigendum: Fragile Gene WWOX Guides TFAP2A/TFAP2C-Dependent Actions Against Tumor Progression in Grade II Bladder Cancer. Frontiers in oncology 4 34513711
2025 Menin facilitates the cell proliferation of bladder cancer via modulating the TFAP2C/β-catenin axis. Genes & diseases 3 40837414
2024 Does TFAP2C govern conflicting cell fates in mouse preimplantation embryos? Reproduction (Cambridge, England) 3 38165360
2024 TFAP2C is a key regulator of intrauterine trophoblast cell invasion and deep hemochorial placentation. JCI insight 3 39625795
2022 Generation of Tfap2c-T2A-tdTomato knock-in reporter rats via adeno-associated virus-mediated efficient gene targeting. Molecular reproduction and development 3 35170139
2024 TFAP2C-DDR1 axis regulates resistance to CDK4/6 inhibitor in breast cancer. Cancer letters 2 39603379
2024 TFAP2C-mediated transcriptional activation of STEAP3 promotes lung squamous cell carcinoma progression by regulating the β-catenin pathway. Biology direct 2 39716275
2026 Propofol attenuates angiogenesis by activating endoplasmic reticulum stress to suppress TFAP2C-driven VEGFA transcription. Apoptosis : an international journal on programmed cell death 1 41524974
2025 TFAP2C drives cisplatin resistance in bladder cancer by upregulating YAP and activating β-catenin signaling. The Journal of biological chemistry 1 40541807
2024 Transcriptional mechanism of E2F1/TFAP2C/NRF1 in regulating KANK2 gene in nephrotic syndrome. Experimental cell research 1 38253280
2024 TFAP2C is a key regulator of intrauterine trophoblast cell invasion and deep hemochorial placentation. bioRxiv : the preprint server for biology 1 39554130
2026 Simultaneous CRISPR-on activation of TFAP2C and SMARCA4 promotes development of trophoblast-fate cells in bovine embryos†. Biology of reproduction 0 41700779
2026 TFAP2C protects against ferroptosis in ovarian cancer through the KEAP1-NRF2 axis by recruiting HDAC1/2. Oncogene 0 41703284
2026 Prion propagation is controlled by a hierarchical network involving the nuclear Tfap2c and hnRNP K factors and the cytosolic mTORC1 complex. PLoS pathogens 0 42008486
2025 Deciphering the role of cis-regulatory elements and TFAP2C in the activation of zygotic Sox2 expression in mouse preimplantation embryos. Development (Cambridge, England) 0 40600821
2025 TFAP2C Affects PI3K/AKT/mTOR Pathway-Mediated EMT for Glioblastoma Development Through Transcriptional Regulation. Cell biology international 0 40667743
2025 TFAP2C activates PTGES through the NOTCH3 signaling pathway to affect gefitinib resistance in lung adenocarcinoma. Journal of clinical biochemistry and nutrition 0 40777819
2025 Single-cell transcriptomics of organoids reveals transcriptional control of germline stem cell fate by an E2F1-TFAP2C-SOX17 positive-feedback loop in Turner syndrome. Cell & bioscience 0 41035077
2024 Regulation of Enhancers by SUMOylation Through TFAP2C Binding and Recruitment of HDAC Complex to the Chromatin. Research square 0 38645262

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