Affinage

FOXA2

Hepatocyte nuclear factor 3-beta · UniProt Q9Y261

Length
457 aa
Mass
48.3 kDa
Annotated
2026-06-09
100 papers in source corpus 44 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/9 claims corpus-supported (89%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FOXA2 (HNF3B) is a winged-helix pioneer transcription factor that opens chromatin at developmental and metabolic enhancers and licenses other transcription factors for DNA binding, thereby controlling endoderm-derived lineage specification and tissue-specific gene programs (PMID:31291575, PMID:23260146). Its DNA-binding domain engages the forkhead consensus (GTAAACA) through helix H3 and wing 1 of the canonical winged-helix fold, with wing 2 required for optimal binding (PMID:28644006). As a pioneer factor it cooperates with the histone variant H2A.Z and Nap1l1-coupled SWI/SNF and INO80 remodelers to deplete nucleosomes at endodermal loci, and during human pancreatic specification it deposits H3K4me1 at enhancers and enables GATA6 recruitment; its binding-site selection is guided by epigenetic priming and TET1-dependent DNA demethylation, and accessibility gains require synergistic co-binding with partner endoderm factors (PMID:23260146, PMID:31291575, PMID:31350899, PMID:35798741). In the pancreas FOXA2 is required for beta-cell identity and glucose-stimulated insulin secretion, directly activating Kir6.2, SUR1, Hadhsc, and ChREBP and cooperating with Insm1, Neurod1, and Neurogenin3 (PMID:15314688, PMID:17908556, PMID:20534694, PMID:25828096, PMID:23471965). In the liver it acts as a chromatin-level co-activator that enables CREB and glucocorticoid-receptor recruitment to gluconeogenic promoters during fasting and drives fatty-acid oxidation and ketogenesis, cooperating with HNF4α and the bile-acid receptor FXR (PMID:16098831, PMID:19822575, PMID:29981427). In the brain it converts the Nurr1-CoREST-HDAC1 repressor complex into an activator complex to drive dopaminergic gene expression (PMID:24496614). FOXA2 nuclear activity and stability are tuned by an extensive set of post-translational modifications: insulin/PI3K/Akt phosphorylation at Thr156 drives cytoplasmic sequestration, glucagon-induced p300 acetylation at Lys259 activates it while SIRT1 deacetylation targets it for proteasomal degradation, SUMO-1 modification at Lys6 stabilizes it, IKKα phosphorylation at Ser107/Ser111 suppresses transactivation, and TRIM36-mediated K48-polyubiquitination drives its degradation (PMID:15616563, PMID:23416070, PMID:24875183, PMID:23118920, PMID:22196886, PMID:37875418). It also operates as a context-dependent tumor suppressor or lineage-reprogramming driver, synergizing epistatically with PI3K/PTEN signaling in endometrium and driving AR-independent adeno-to-neuroendocrine transitions in prostate cancer via JUN/LSD1-dependent enhancer reprogramming (PMID:35703180, PMID:36332622, PMID:38851846). A de novo p.S169P mutation in the DNA-binding domain causes congenital hyperinsulinism and hypopituitarism with endoderm-organ abnormalities (PMID:28973288).

Mechanistic history

Synthesis pass · year-by-year structured walk · 36 steps
  1. 2004 High

    Established that insulin signaling inactivates FOXA2 not by altering its expression but by spatial regulation, defining a phosphorylation-controlled nucleocytoplasmic switch over its metabolic program.

    Evidence Adenoviral Foxa2T156A phospho-mutant expression with nuclear/cytoplasmic fractionation in insulin-resistant mice

    PMID:15616563

    Open questions at the time
    • Identity of the precise Akt-FOXA2 cytoplasmic-retention machinery not resolved
    • Does not address PTM crosstalk with later-discovered acetylation/sumoylation
  2. 2004 High

    Showed FOXA2 is required for beta-cell secretory competence by directly controlling K-ATP channel subunits and a metabolic target, linking the factor to insulin-secretion physiology.

    Evidence Beta-cell-specific conditional Foxa2 knockout with islet functional assays, ChIP, and reporter assays on Hadhsc

    PMID:15314688

    Open questions at the time
    • Direct vs. indirect regulation of Kir6.2/SUR1 not fully separated
    • Pioneer-factor role at these loci not yet defined
  3. 2005 High

    Defined FOXA2 as a chromatin-level co-activator that integrates cAMP and glucocorticoid signals by enabling CREB and GR occupancy at gluconeogenic promoters during fasting.

    Evidence Hepatocyte conditional Foxa2 ablation with ChIP for CREB and GR at gluconeogenic promoters

    PMID:16098831

    Open questions at the time
    • Whether FOXA2 directly opens chromatin or recruits co-factors not mechanistically separated here
    • Stoichiometry of FOXA2/CREB/GR complex unknown
  4. 2005 Medium

    Demonstrated mutual recruitment between FOXA2 and the androgen receptor, an early indication that FOXA proteins direct nuclear-receptor cistromes.

    Evidence GST pull-down, EMSA, ChIP, and reporter assays; epididymis mE-RABP promoter

    PMID:16467259

    Open questions at the time
    • Structural basis of FOXA2-AR DBD interaction not resolved
    • Genome-wide generality not established in this study
  5. 2009 Medium

    Extended FOXA2 partnerships to hepatic master regulators, showing genome-wide co-occupancy with HNF4α at thousands of regulatory elements.

    Evidence ChIP-seq for FOXA2, HNF4α, GABP plus co-IP

    PMID:19822575

    Open questions at the time
    • Direct FOXA2-HNF4α physical interaction not demonstrated by reciprocal co-IP
    • Functional consequence of co-occupancy not tested by perturbation
  6. 2009 High

    Defined FOXA1/2 as developmental terminators of bile-duct expansion through enabling GR-mediated repression of IL-6.

    Evidence Liver-specific Foxa1/2 double conditional KO with GR ChIP at IL-6 promoter

    PMID:19436110

    Open questions at the time
    • Direct FOXA-GR interaction at IL-6 not biochemically shown
    • Redundancy between FOXA1 and FOXA2 not separated
  7. 2009 Medium

    Placed FOXA1/2 in midbrain dopaminergic specification as direct regulators of TH, Nkx2.2, and Shh-pathway feedforward loops.

    Evidence Conditional Foxa1/2 KO with ChIP for Foxa2 at Nkx2.2/TH and Gli2 loci

    PMID:19607821 PMID:21093585

    Open questions at the time
    • Direct vs. indirect repression of Gli2/Nkx2.2 not fully dissected
    • Co-factor requirements for repression unknown
  8. 2009 Medium

    Revealed FOXA2 controls endoderm epithelialization and polarity, linking the factor to morphogenesis beyond gene transcription.

    Evidence Foxa2 conditional KO with polarity/junction immunostaining and time-lapse imaging

    PMID:19234065

    Open questions at the time
    • Transcriptional targets driving polarity not identified
    • Cell-autonomy not fully resolved
  9. 2011 High

    Identified a kinase that suppresses FOXA2 transactivation, connecting inflammatory TNFα/IKKα signaling to the FOXA2/NUMB/NOTCH1 axis in liver cancer.

    Evidence IKKα-FOXA2 co-IP, phospho-Ser107/111 detection, transactivation reporters, knockdown and tumor analysis

    PMID:22196886

    Open questions at the time
    • Direct kinase-substrate phosphorylation in vitro not the sole readout
    • Effect on FOXA2 DNA binding vs. co-factor recruitment not separated
  10. 2012 High

    Defined the pioneer mechanism: FOXA2 with H2A.Z drives nucleosome depletion at endodermal loci via Nap1l1-coupled SWI/SNF and INO80, with DNA methylation opposing accessibility.

    Evidence MNase-seq, ChIP-seq, Foxa2 knockdown during ESC-to-endoderm differentiation, remodeler inhibition

    PMID:23260146

    Open questions at the time
    • Direct FOXA2-remodeler contacts not biochemically defined
    • Order of H2A.Z deposition vs. FOXA2 binding unresolved
  11. 2012 High

    Showed FOXA2 stability is positively controlled by SUMO-1 modification at Lys6, adding a degradation-protective PTM layer.

    Evidence K6R mutagenesis, SUMO-1 fusion rescue, UBC9 knockdown, PIAS1 co-IP, reporter assays across cell lines

    PMID:23118920

    Open questions at the time
    • Physiological signal driving sumoylation not identified
    • Crosstalk with ubiquitination machinery not mapped
  12. 2013 High

    Established glucagon-induced Lys259 acetylation as a positive activity switch with p300 as writer and SIRT1 as eraser, opposing the insulin-driven inhibition.

    Evidence K259Q/K259R mutagenesis, HDAC inhibition, p300/SirT1 co-IP, adenoviral in vivo expression

    PMID:23416070

    Open questions at the time
    • How acetylation alters FOXA2 chromatin engagement not resolved
    • Integration with Thr156 phosphorylation not mechanistically linked
  13. 2014 High

    Clarified SIRT1 as a nutrient-responsive regulator that deacetylates FOXA2 and targets it for proteasomal turnover, coupling fasting signals to FOXA2 stability.

    Evidence LC-MS/MS acetyl-site mapping, SIRT1-FOXA2 co-IP, reporter assays, murine starvation model

    PMID:24875183

    Open questions at the time
    • E3 ligase coupling SIRT1 deacetylation to degradation not identified here
    • Apparent context-dependence vs. SIRT1's positive role on Pdx1 unresolved
  14. 2013 Medium

    Showed SIRT1-FOXA2 cooperation can also be activating, forming a complex on the Pdx1 promoter required for islet development.

    Evidence Co-IP, ChIP on Pdx1 promoter, pancreas-specific Sirt1 KO mice

    PMID:24163589

    Open questions at the time
    • Reconciliation with SIRT1-driven FOXA2 degradation elsewhere not addressed
    • Direct vs. indirect Pdx1 effect not fully separated
  15. 2017 High

    Provided the structural basis of FOXA2 DNA recognition, localizing specificity to helix H3 and wing 1 and showing wing 2 contributes to affinity.

    Evidence 2.8 Å co-crystal of FOXA2 DBD with consensus DNA and ITC for wing 2 deletion

    PMID:28644006

    Open questions at the time
    • Structure of full-length factor or nucleosome-bound complex not solved
    • Basis of pioneer activity not captured by naked-DNA structure
  16. 2017 Medium

    Linked FOXA2 directly to human Mendelian disease through a DNA-binding-domain mutation impairing transactivation and protein stability.

    Evidence Whole-exome sequencing of patients; WT vs. p.S169P reporter and western blot in HEK293T

    PMID:28973288

    Open questions at the time
    • Functional validation limited to transient transfection reporters
    • In vivo recapitulation of patient phenotype not shown
  17. 2019 High

    Demonstrated FOXA2 is the pioneer factor priming pancreatic enhancers (H3K4me1) and enabling GATA6 recruitment during human pancreatic specification.

    Evidence CRISPR FOXA2 KO in hPSCs with ATAC-seq, H3K4me1/GATA6 ChIP-seq, directed differentiation

    PMID:31291575

    Open questions at the time
    • Direct FOXA2-GATA6 interaction not biochemically tested
    • Mechanism of H3K4me1 deposition (which methyltransferase) unresolved
  18. 2019 High

    Refined the pioneer model: epigenetic priming directs FOXA2 site selection and binding alone is insufficient for opening, which requires synergistic co-binding factors.

    Evidence ATAC-seq, ChIP-seq for active marks, ectopic Foxa2 expression in ESCs with genome-wide binding

    PMID:31350899

    Open questions at the time
    • Identity of all required co-binding partners not enumerated
    • Quantitative threshold for productive opening not defined
  19. 2022 High

    Connected DNA demethylation to FOXA2 pioneering, showing TET1 physically interacts with FOXA2 and is required for its binding at pancreatic enhancers.

    Evidence TET triple-KO hESCs, WGBS, ATAC-seq, ChIP-seq, TET1-FOXA2 co-IP, beta-cell differentiation

    PMID:35798741

    Open questions at the time
    • Whether FOXA2 recruits TET1 or vice versa not resolved
    • Direct demethylation at FOXA2 sites vs. global effects not separated
  20. 2007 High

    Revealed a repressive FOXA2 role in mature beta cells, where its loss enlarges the docked granule pool and enhances first-phase secretion via trafficking genes.

    Evidence Inducible Pdx1-CreERT2 Foxa2 ablation with EM, Ca2+/cAMP measurement, expression profiling

    PMID:17908556

    Open questions at the time
    • Direct trafficking-gene targets not all mapped
    • Reconciliation with FOXA2's earlier activating role not addressed
  21. 2010 High

    Showed FOXA1/FOXA2 redundancy and a direct ChREBP target underlying beta-cell glucose homeostasis.

    Evidence Inducible double conditional KO, islet secretion and Ca2+ assays, ChIP at ChREBP promoter

    PMID:20534694

    Open questions at the time
    • Degree of FOXA1/2 functional non-equivalence not quantified
    • Downstream metabolic consequences of ChREBP loss not fully traced
  22. 2014 Medium

    Identified FOXA1/2 control of glucagon-gene expression and an alpha-cell-specific FOXA2 target set, extending its role across both islet endocrine lineages.

    Evidence siRNA knockdown in alpha cells, ChIP at multiple promoters, glucagon secretion assays

    PMID:25057789

    Open questions at the time
    • Mechanism of FOXA2-specific (vs FOXA1) target selectivity unknown
    • In vivo alpha-cell phenotype not tested
  23. 2014 Medium

    Placed FOXA2 within a TXNIP/miR-124a regulatory cascade controlling IAPP transcription in beta cells.

    Evidence ChIP at IAPP promoter, luciferase assays, miR-124a manipulation, beta-cell Txnip KO mice

    PMID:24627476

    Open questions at the time
    • Direct FOXA2 regulation by miR-124a vs. indirect not fully separated
    • Relevance to amyloid pathology not established
  24. 2014 High

    Defined a neuronal co-activator mechanism: FOXA2 converts the Nurr1-CoREST-HDAC1 repressor into an activator complex, opening dopaminergic gene chromatin.

    Evidence Nurr1/CoREST/Foxa2 co-IP, ChIP for CoREST/Hdac1/H3Ac, reporters, neural precursor differentiation

    PMID:24496614

    Open questions at the time
    • Structural basis of complex switching not resolved
    • Generality beyond dopaminergic promoters not tested
  25. 2015 High

    Identified combinatorial maturation circuitry in beta cells, with Insm1, Neurod1, and FOXA2 physically interacting and co-occupying maturity genes.

    Evidence Co-IP, ChIP-seq for all three factors, Insm1 conditional KO, expression profiling

    PMID:25828096

    Open questions at the time
    • Order of complex assembly on chromatin not resolved
    • Pairwise vs. ternary binding requirements not dissected
  26. 2015 Medium

    Placed FOXA2 in an anterior-mesendoderm developmental complex with Lhx1, Otx2, and the chromatin-looper Ldb1.

    Evidence Proteomic co-IP and ChIP-seq for Lhx1/Otx2/Foxa2, conditional Lhx1 inactivation

    PMID:26494787

    Open questions at the time
    • Direct binary FOXA2 contacts within the complex not mapped
    • Functional requirement of FOXA2 within Ldb1 looping not isolated
  27. 2018 Medium

    Added a non-genomic arm of hepatic gluconeogenic control, with glucagon-activated FOXA2 physically inhibiting FXR-mediated SHP induction.

    Evidence Pull-down, ChIP-seq, Foxa2 knockdown in primary hepatocytes, transactivation assays, FXR mutagenesis

    PMID:29981427

    Open questions at the time
    • Interaction surface on FOXA2 not mapped
    • In vivo contribution to fasting glycemia not quantified
  28. 2022 High

    Established FOXA2 as a tumor suppressor that synergizes epistatically with PI3K/PTEN, acting through enhancer modification in endometrial epithelium.

    Evidence Conditional Foxa2/Pten single and double KO mice, RNA-seq, ChIP-seq, organoids, cell assays

    PMID:35703180

    Open questions at the time
    • Mechanistic link between FOXA2 loss and PI3K hyperactivation not fully defined
    • Key suppressed enhancer targets not pinpointed
  29. 2019 High

    Showed FOXA2 cistrome and regulated programs are grade-specific in pancreatic cancer, set by differential co-binding partners despite constant expression.

    Evidence ChIP-seq and ATAC-seq across PDAC lines with knockdown validation

    PMID:31531882

    Open questions at the time
    • Identity of grade-specific partner factors not fully resolved
    • Drivers of differential FOXA2 recruitment unknown
  30. 2020 Medium

    Identified upstream epigenetic activation of FOXA2 by PHF8 in neuroendocrine prostate cancer.

    Evidence PHF8 KO in TRAMP mice, ChIP for repressive marks at FOXA2 promoter, xenografts

    PMID:33009820

    Open questions at the time
    • Direct PHF8 demethylation at FOXA2 promoter vs. indirect not separated
    • Generality across NEPC models not tested
  31. 2022 High

    Established FOXA2 as a driver of prostate adeno-to-neuroendocrine lineage transition induced by androgen deprivation, acting through the KIT pathway.

    Evidence Single-cell multiomics in GEMMs, FOXA2 knockdown rescue, KIT inhibition, human NEPC analysis

    PMID:36332622

    Open questions at the time
    • Direct vs. indirect KIT regulation not fully separated
    • Initiating trigger of FOXA2 induction not defined
  32. 2024 High

    Defined the mechanism of FOXA2 lineage reprogramming in AR-independent prostate cancer through LSD1-dependent enhancer binding and JUN/AP-1 collaboration.

    Evidence FOXA2/JUN ChIP-seq, ATAC-seq, LSD1 inhibition, FOXA2 overexpression in PCa lines

    PMID:38851846

    Open questions at the time
    • Direct FOXA2-LSD1 and FOXA2-JUN physical contacts not biochemically mapped
    • Reversibility of reprogrammed states not tested
  33. 2023 Medium

    Added a degradation pathway: the E3 ligase TRIM36 drives K48-polyubiquitination and proteasomal turnover of FOXA2, linking FOXA2 levels to ferroptosis control via NRF2/GPX4.

    Evidence TRIM36-FOXA2 co-IP, K48 ubiquitination assays, FOXA2 depletion, NRF2/GPX4 analysis in colorectal cells

    PMID:37875418

    Open questions at the time
    • Ubiquitination acceptor lysines on FOXA2 not mapped
    • Direct vs. indirect NRF2/GPX4 regulation not separated
  34. 2021 Medium

    Identified a cardioprotective transcriptional-repressor role, with FOXA2 directly silencing RIPK3 to limit necroptosis via the CNEACR/HDAC7/Foxa2 axis.

    Evidence ChIP at RIPK3 promoter, FOXA2 OE/KD in cardiomyocytes, H/R injury model, HDAC7 fractionation

    PMID:34588633

    Open questions at the time
    • Direct repression mechanism (co-repressor recruitment) not defined
    • Generality to in vivo ischemia not fully established
  35. 2010 Medium

    Linked FOXA2 to immune homeostasis, showing respiratory-epithelial FOXA2 suppresses Th2 inflammation via a defined cytokine/chemokine program.

    Evidence Respiratory-epithelium Foxa2 conditional KO with cytokine profiling, flow cytometry, anti-IL-4Rα rescue

    PMID:20483781

    Open questions at the time
    • Direct FOXA2 cytokine-gene targets not all defined
    • Whether repression is direct or indirect unresolved
  36. 2013 Medium

    Showed FOXA2 stability is regulated by Hippo kinases Mst1/2 in lung, required for pneumocyte differentiation and surfactant expression, independent of YAP.

    Evidence Mst1/2 conditional KO mice, Foxa2 phosphorylation/co-IP assays, surfactant gene analysis

    PMID:23620511

    Open questions at the time
    • Phosphosite(s) mediating Mst1/2 stabilization not mapped
    • Mechanism of stabilization (degradation block) unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the diverse PTM inputs (Thr156 phosphorylation, Lys259 acetylation, Lys6 sumoylation, Ser107/111 phosphorylation, K48 ubiquitination) are integrated into a single quantitative control of FOXA2 activity, and what structural basis allows the same factor to act as activator, repressor, tumor suppressor, and lineage-reprogramming oncogenic driver across tissues.
  • No structure of FOXA2 engaging a nucleosome to explain pioneer activity
  • No unified model reconciling context-dependent activating vs. repressive and tumor-suppressive vs. oncogenic roles
  • Direct physical contacts to most named co-factors not biochemically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 3 GO:0140097 catalytic activity, acting on DNA 2
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1430728 Metabolism 4 R-HSA-1643685 Disease 4 R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 3
Partners
FXRGATA6HNF4AINSM1JUNNURR1SIRT1TET1
Complex memberships
Insm1-Neurod1-FOXA2 beta-cell maturity complexLhx1-Otx2-FOXA2-Ldb1 anterior mesendoderm complexNurr1-FOXA2 dopaminergic activator complex

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Insulin signaling causes nuclear exclusion of Foxa2 (phosphorylation-dependent cytoplasmic localization), inactivating its transcriptional program; a constitutively nuclear Foxa2T156A mutant (cannot be phosphorylated by insulin/PI3K/Akt) activates lipid oxidation, ketogenesis, and glycolysis gene programs in the liver, demonstrating that insulin inhibits Foxa2 by nuclear exclusion. Adenoviral expression of Foxa2T156A in insulin-resistant mice; nuclear/cytoplasmic fractionation; gene expression analysis Nature High 15616563
2005 Foxa2 is required in hepatocytes for activation of gluconeogenic gene programs during fasting; it acts as a chromatin-level co-activator enabling recruitment of CREB and glucocorticoid receptor (GR) to their target sites, integrating cAMP and glucocorticoid hormone signals. Cell-type-specific Foxa2 gene ablation; chromatin immunoprecipitation (ChIP) for CREB and GR occupancy at gluconeogenic promoters Cell metabolism High 16098831
2013 Glucagon induces acetylation of Foxa2 at the conserved residue Lys259; the co-activator p300 acetylates Foxa2 and SirT1 deacetylates it; acetylation-mimicking mutation K259Q increases Foxa2 transcriptional activity on fatty acid oxidation and ketogenesis genes, while K259R reduces it, establishing glucagon-induced acetylation as a positive regulatory PTM. Site-directed mutagenesis (K259Q/K259R); HDAC inhibitor treatment; co-immunoprecipitation of p300 and SirT1 with Foxa2; adenoviral expression in mice; gene expression analysis Cell metabolism High 23416070
2014 SIRT1 physically interacts with FOXA2, deacetylates it in a nutrient-dependent manner, and targets it for proteasomal degradation; during starvation, the SIRT1-FOXA2 interaction is reduced, FOXA2 acetylation increases, and FOXA2 is stabilized, enabling its transcriptional program (G6pase, CPT1a) in liver. LC-MS/MS identification of five acetylated FOXA2 residues; co-IP of SIRT1 with FOXA2; siRNA knockdown of UBC9; promoter-reporter assays; murine starvation model PloS one High 24875183
2013 SIRT1 forms a protein complex with FOXA2 on the Pdx1 gene promoter; SIRT1 deacetylates FOXA2 and positively regulates Pdx1 transcription in pancreatic beta cells; pancreas-specific SIRT1 disruption diminishes PDX1 expression and impairs islet development. Co-immunoprecipitation; ChIP on Pdx1 promoter; pancreas-specific Sirt1 knockout mice International journal of biological sciences Medium 24163589
2011 IKKα (downstream of TNFα) phosphorylates FOXA2 at Ser107/Ser111, suppressing FOXA2 transactivation activity, reducing NUMB expression, and consequently activating NOTCH1 signaling to promote hepatocellular carcinoma cell proliferation; this defines a TNFα/IKKα/FOXA2/NUMB/NOTCH1 pathway. Co-immunoprecipitation of IKKα with FOXA2; phospho-specific antibody staining; transactivation reporter assays; knockdown experiments in cell lines and tumor tissue analysis Molecular cell High 22196886
2012 FOXA2 is sumoylated at Lys6 by SUMO-1; preventing sumoylation (K6R mutation) destabilizes FOXA2 protein (promotes proteasomal degradation) without affecting nuclear localization; PIAS1 SUMO ligase increases FOXA2 levels and transcriptional activity on Pdx-1 enhancer; UBC9 knockdown reduces FOXA2 protein levels. Site-directed mutagenesis (K6R); SUMO-1 in-frame fusion rescue; siRNA knockdown of UBC9; co-immunoprecipitation with PIAS1; promoter-reporter assays in INS-1E, HepG2, and other cell lines PloS one High 23118920
2004 Foxa2 is required in pancreatic beta cells for expression of both Kir6.2 and SUR1 (ATP-sensitive K+ channel subunits) and Hadhsc; Foxa2 directly binds and activates the Hadhsc promoter; loss of Foxa2 causes excessive insulin release to amino acids and complete loss of glucose-stimulated insulin secretion. Conditional beta-cell-specific Foxa2 deletion; isolated islet functional assays; RNA in situ hybridization; chromatin immunoprecipitation; cotransfection reporter assays The Journal of clinical investigation High 15314688
2007 Inducible deletion of Foxa2 in mature beta cells increases the docked insulin granule pool and first-phase glucose-stimulated insulin secretion; Foxa2 regulates expression of multiple genes in vesicular trafficking and membrane targeting, and its loss alters intracellular Ca2+ oscillations and elevates cAMP. Inducible Foxa2 gene ablation (Pdx1-CreERT2); electron microscopy of granule pools; Ca2+ oscillation measurements; cAMP measurement; expression profiling Cell metabolism High 17908556
2010 Simultaneous inducible ablation of Foxa1 and Foxa2 in mature beta cells impairs glucose homeostasis and insulin secretion more severely than loss of Foxa2 alone; both factors directly regulate ChREBP (Mlxipl) expression in fetal endocrine pancreas and adult islets. Inducible double conditional KO; isolated islet secretion assays; Ca2+ oscillation measurements; ChIP for Foxa1/Foxa2 at ChREBP promoter; expression profiling Molecular endocrinology High 20534694
2015 Insm1, Neurod1, and Foxa2 physically interact and co-occupy regulatory sequences in mature pancreatic beta-cell genomes; combinatorial binding of all three factors explains a significant fraction of gene expression changes needed to maintain beta-cell maturity. Co-immunoprecipitation of Insm1 with Neurod1 and Foxa2; ChIP-seq for all three factors; Insm1 beta-cell-specific ablation; gene expression profiling The EMBO journal High 25828096
2017 Crystal structure (2.8 Å) of the FOXA2 DNA-binding domain bound to the forkhead consensus site (GTAAACA) shows helix H3 and wing 1 mediate DNA recognition via the canonical winged-helix fold, with more major-groove and fewer minor-groove contacts than FOXA3; wing 2 is required for optimal binding (ITC). X-ray crystallography (2.8 Å co-crystal); isothermal titration calorimetry (ITC) for wing 2 deletion Biochemistry High 28644006
2012 Foxa2 and the histone variant H2A.Z cooperate to mediate nucleosome depletion at endodermal gene loci during ES cell differentiation into endoderm; nucleosome depletion is dependent on Nap1l1-coupled SWI/SNF and INO80 chromatin remodeling complexes; DNA methylation promotes nucleosome occupation and suppresses gene expression. MNase-seq for nucleosome occupancy; Foxa2 knockdown during ES differentiation; ChIP-seq; pharmacological inhibition of SWI/SNF and INO80 Cell High 23260146
2019 FOXA2 is required as a pioneer factor for chromatin opening and H3K4me1 deposition (enhancer priming) during human pancreatic specification; FOXA2 KO in hPSCs reduces pancreatic progenitor numbers and impairs GATA6 recruitment to pancreatic enhancers. CRISPR/Cas9 FOXA2 knockout in hPSCs; ATAC-seq; ChIP-seq for H3K4me1 and GATA6; directed pancreatic differentiation Cell reports High 31291575
2019 Pioneer factor Foxa2 binding site selection is directed by epigenetic priming (low levels of active chromatin marks in ESCs); Foxa2 binding alone is not sufficient for chromatin opening—increased accessibility requires synergistic co-binding with other endoderm transcription factors. ATAC-seq; ChIP-seq for active chromatin marks; ectopic Foxa2 expression in ESCs followed by genome-wide binding analysis Nucleic acids research High 31350899
2022 TET1 dioxygenase physically interacts with FOXA2 in endodermal lineage intermediates; TET depletion reduces FOXA2 binding at pancreatic progenitor enhancers; TET1-dependent DNA demethylation is required for FOXA2-associated chromatin remodeling during beta-cell differentiation. TET1/2/3 triple knockout hESCs; WGBS; ATAC-seq; ChIP-seq; co-immunoprecipitation of TET1 with FOXA2; directed beta-cell differentiation Nature communications High 35798741
2005 Foxa1 and Foxa2 physically interact with the DNA-binding domain of the androgen receptor (AR); both Foxa proteins can be recruited to AR binding sites in the absence of Foxa consensus sequences, and AR is recruited to Foxa binding sites in the absence of an AR binding site, indicating mutual recruitment; Foxa2 (but not Foxa1) is expressed in the epididymis and binds the mE-RABP promoter. GST pull-down assay; gel-shift (EMSA); chromatin immunoprecipitation (ChIP); co-transfection reporter assays Annals of the New York Academy of Sciences Medium 16467259
2009 Foxa1 and Foxa2 are required for normal bile duct development; in their absence, glucocorticoid receptor fails to bind the IL-6 promoter, causing enhanced IL-6 expression and cholangiocyte hyperproliferation; Foxa1/2 thus function as terminators of bile duct expansion by enabling GR-mediated repression of IL-6. Conditional double Foxa1/2 liver-specific knockout; ChIP for glucocorticoid receptor at IL-6 promoter; gene expression analysis The Journal of clinical investigation High 19436110
2009 Foxa1/2 chromatin immunoprecipitation indicates that Nkx2.2 and tyrosine hydroxylase (TH) genes are direct targets in mesodiencephalic dopaminergic cells; Foxa1 and Foxa2 positively regulate Lmx1a and Lmx1b and inhibit Nkx2.2, and function cooperatively with Lmx1a/Lmx1b in a feedforward loop for DA neuron differentiation. Conditional Foxa1/2 knockout mice; chromatin immunoprecipitation for Foxa2 at Nkx2.2 and TH loci; gene expression analysis Developmental biology Medium 19607821
2010 Foxa2 directly binds Gli2 genomic regions (ChIP) and represses Gli2 transcription, thereby attenuating Shh signaling in ventral midbrain progenitors; Foxa1 and Foxa2 both positively and negatively regulate Shh pathway components to specify ventral midbrain progenitor identity. Conditional Foxa2 knockout in midbrain (Wnt1-Cre); gain-of-function studies; ChIP for Foxa2 at Gli2 locus; gene expression analysis Mechanisms of development Medium 21093585
2014 Foxa2 acts as a co-activator of Nurr1-induced dopaminergic (DA) gene expression by displacing the Nurr1-CoREST repressor complex; in the presence of Foxa2, Nurr1 forms an activator complex with Foxa2 instead, reducing CoREST/Hdac1 enrichment at DA gene promoters and increasing H3 acetylation (open chromatin) at those promoters. Co-immunoprecipitation of Nurr1 with CoREST and Foxa2; ChIP for CoREST, Hdac1 and H3Ac at DA gene promoters; reporter assays; neural precursor cell differentiation Development High 24496614
2009 FOXA2 and HNF4α co-occupy thousands of genomic regulatory elements in hepatocytes; co-immunoprecipitation confirmed a physical interaction between HNF4α and GABP at transcription start sites, and HNF4α/FOXA2 frequently co-occupy distal elements together with USF2. ChIP-seq for FOXA2, HNF4α, and GABP; co-immunoprecipitation of HNF4α and GABP Nucleic acids research Medium 19822575
2009 Foxa2 regulates polarity and epithelialization of endoderm cells; Foxa2-mutant endodermal cells fail to maintain apical-basal polarity and cannot establish proper cellular junctions, preventing integration into the endoderm epithelium, indicating Foxa2 promotes an epithelial fate and suppresses a mesenchymal fate. Foxa2 conditional knockout; immunohistochemistry for polarity/junction markers; time-lapse confocal imaging Development Medium 19234065
2012 Foxa1/2 deficiency in the liver abolishes the sexual dimorphism of hepatocellular carcinoma; Foxa1/2 are required for co-regulation of target genes by either ERα (in females) or the androgen receptor (AR) (in males) during hepatocarcinogenesis; FOXA2 binding site SNPs reduce co-occupancy of FOXA2 and ERα in human liver. Conditional double Foxa1/2 knockout after DEN-induced hepatocarcinogenesis; ChIP-seq for Foxa1/2, ERα, and AR; SNP analysis of FOXA2 binding sites Cell High 22265403
2018 FOXA2 physically interacts with FXR (farnesoid X receptor/bile acid receptor) in hepatocytes; glucagon-activated FOXA2 inhibits FXR's ability to induce SHP (an anti-gluconeogenic nuclear receptor) through this protein-protein interaction; this represents a second arm of FXR regulation in fasting hepatic gluconeogenesis. In vitro protein-protein interaction assays (pull-down); cistromic (ChIP-seq) analysis; Foxa2 knockdown in primary hepatocytes; transactivation assays; site-directed mutagenesis of FXR Journal of hepatology Medium 29981427
2013 Neurogenin3 (Neurog3) can autoactivate its own expression; Foxa2 cooperates synergistically with Neurogenin3 to amplify this autoregulation in vitro; Foxa2 colocalizes with Neurogenin3 in pancreatic progenitors in vivo; Foxa2 RNAi attenuates Neurogenin3-dependent activation of the endocrine developmental program. ChIP for Neurogenin3 at its own upstream region; reporter assays with Foxa2 co-expression; RNA interference of Foxa2 in mPAC cells; immunofluorescence co-localization in embryonic pancreas The Journal of biological chemistry Medium 23471965
2009 Foxa2 regulates hepatic gene networks in a physiological-state-dependent manner by interacting with different transcription factor partners depending on the presence or absence of cholic acid; distinct feedforward regulatory loops control Foxa2-dependent targets under different physiological conditions. Foxa2 liver-specific knockout; functional genomics (expression profiling under cholic acid diet); co-immunoprecipitation with partner transcription factors Physiological genomics Medium 19417011
2012 β-catenin signaling directly regulates Foxa2 expression in uterine epithelia; Foxa2 knockdown in uterine epithelial cells causes defects in cell cycle regulation, suggesting a role for Foxa2 in controlling cell proliferation downstream of β-catenin. Conditional β-catenin ablation/activation in uterus; ChIP for β-catenin at Foxa2 locus; siRNA knockdown of Foxa2; cell cycle analysis Oncogene Medium 22945641
2012 GATA6 and FOXA2 directly bind the Wnt6 promoter and cooperate to activate Wnt6 gene expression during extraembryonic endoderm formation, thereby activating the canonical WNT-β-catenin pathway. Chromatin immunoprecipitation; reporter assay with GATA6/FOXA2 overexpression; F9 teratocarcinoma cell differentiation model Stem cells and development Medium 22607194
2019 FOXA2 controls distinct cis-regulatory networks in well- vs. poorly-differentiated pancreatic ductal adenocarcinoma cells via grade-specific partnerships with different co-binding transcription factors, despite being expressed in both cell types; FOXA2 genomic distribution and regulated gene programs differ extensively by differentiation grade. ChIP-seq for FOXA2 in multiple PDAC cell lines; ATAC-seq; transcriptome analysis; FOXA2 knockdown The EMBO journal High 31531882
2020 PHF8 histone demethylase transcriptionally upregulates FOXA2 by demethylating repressive histone marks on the FOXA2 promoter; PHF8 is required for neuroendocrine prostate cancer (NEPC) development and acts upstream of FOXA2 in the NEPC transcriptional program. PHF8 knockout in TRAMP mice; ChIP for repressive histone marks at FOXA2 promoter; gene expression analysis; xenograft models The Journal of pathology Medium 33009820
2022 FOXA2 drives prostate cancer adeno-to-neuroendocrine lineage transition; FOXA2 expression is induced by androgen deprivation; FOXA2 knockdown reverses the transition; FOXA2 directly regulates the KIT pathway, which is specifically activated in neuroendocrine prostate cancer. Single-cell multiomics (scRNA-seq + ATAC-seq) in genetically engineered mouse models; FOXA2 knockdown; KIT pathway inhibition experiments; human NEPC tumor analysis Cancer cell High 36332622
2024 FOXA2 acts as a pioneer factor that binds distinct classes of developmental enhancers in AR-independent prostate cancer subtypes in an LSD1-dependent manner; FOXA2 collaborates with JUN at chromatin to reprogram AP-1 transcriptional activity, driving cell state transitions to multiple cancer lineages. ChIP-seq for FOXA2 and JUN; ATAC-seq; LSD1 inhibition; FOXA2 overexpression in multiple PCa cell lines Nature communications High 38851846
2021 In cardiomyocytes, FOXA2 directly represses RIPK3 gene transcription by binding its promoter region; loss of FOXA2 (through HDAC7-dependent suppression) increases RIPK3-dependent necroptosis; this pathway is governed by the CNEACR/HDAC7/Foxa2/RIPK3 axis. ChIP showing FOXA2 occupancy at RIPK3 promoter; FOXA2 overexpression/knockdown in cardiomyocytes; H/R injury model; HDAC7 nuclear/cytoplasmic fractionation Cell death and differentiation Medium 34588633
2014 TXNIP increases FoxA2 expression, which then binds the proximal FoxA2 site in the IAPP promoter to activate IAPP transcription; TXNIP also downregulates miR-124a, relieving miR-124a-mediated suppression of FoxA2; thus TXNIP controls IAPP expression via a TXNIP/miR-124a/FoxA2/IAPP cascade. Chromatin immunoprecipitation of FoxA2 at IAPP promoter; luciferase reporter assays; miR-124a overexpression/knockdown; beta-cell-specific Txnip knockout mice The Journal of biological chemistry Medium 24627476
2011 Foxa2 binds specific DNA sequences in the cIAP1 promoter and activates cIAP1 transcription; Foxa2 overexpression decreases hepatocyte apoptosis while siRNA silencing increases it, suggesting Foxa2 modulates hepatic apoptosis through the cIAP1 pathway. EMSA and gel supershift assay; ChIP for Foxa2 at cIAP1 promoter; deletion reporter assays; siRNA knockdown; Foxa2 overexpression in HepG2 cells Cellular signalling Medium 23275033
2013 Hippo kinases Mst1/2 stabilize and phosphorylate Foxa2 in respiratory epithelial cells; Mst1/2 conditional knockout mice develop perinatal respiratory failure with defects in pneumocyte differentiation and surfactant protein expression attributed to reduced/destabilized Foxa2, independently of YAP. Mst1/2 conditional knockout mice; co-immunoprecipitation/phosphorylation assay of Foxa2 by Mst1/2; histological and molecular analysis of surfactant gene expression Proceedings of the National Academy of Sciences of the United States of America Medium 23620511
2022 FOXA2 broadly controls gene expression programs in endometrial epithelial cells through modification of enhancer activity (not only direct promoter binding); simultaneous conditional inactivation of Foxa2 and Pten in endometrial epithelium causes lethal endometrial cancers with complete penetrance, establishing epistatic synergism between Foxa2 tumor suppressor and PI3K signaling. Conditional Foxa2 and Pten single/double knockout mice; RNA-seq; ChIP-seq (cistrome); organoid models; cell line functional assays The Journal of clinical investigation High 35703180
2017 A de novo FOXA2 mutation (p.S169P) within the DNA-binding domain impairs FOXA2 transcriptional reporter activity and reduces protein levels, causing congenital hyperinsulinism and hypopituitarism with endoderm-derived organ abnormalities in humans. Whole-exome sequencing; transient transfection reporter assays in HEK293T cells with WT vs. mutant FOXA2; western blot for protein levels Human molecular genetics Medium 28973288
2010 Foxa2 expression in respiratory epithelial cells suppresses Th2 cell-mediated pulmonary inflammation; deletion of Foxa2 induces expression of IL-13, IL-4, eotaxins, Il33, and Ccl20, recruiting myeloid dendritic cells and Th2 cells; pulmonary inflammation was abrogated by anti-IL-4Rα antibody treatment. Respiratory epithelial cell-specific Foxa2 conditional knockout; cytokine/chemokine gene expression; flow cytometry for immune cell infiltrates; anti-IL-4Rα antibody rescue Journal of immunology Medium 20483781
2015 Lhx1, Otx2, and Foxa2 form a protein complex with the chromatin-looping protein Ldb1 in anterior mesendoderm; this complex was characterized by proteomic co-immunoprecipitation and co-regulates development of anterior mesendoderm, node, and midline populations. Co-immunoprecipitation/proteomics; ChIP-seq for Lhx1, Otx2, Foxa2; conditional Lhx1 inactivation Genes & development Medium 26494787
2023 TRIM36, an E3 ubiquitin ligase, directly interacts with FOXA2 and induces its K48-linked polyubiquitination, leading to FOXA2 proteasomal degradation; FOXA2 positively regulates NRF2 pathway activation and GPX4 levels in colorectal cancer cells to suppress ferroptosis. Co-immunoprecipitation of TRIM36 with FOXA2; ubiquitination assays (K48-linkage); FOXA2 depletion by siRNA/CRISPR; NRF2/GPX4 expression analysis Advanced science Medium 37875418
2010 The Siah2 ubiquitin ligase controls HIF-1α availability; HIF-1α forms a transcriptional complex with FoxA2, and this complex drives expression of neuroendocrine prostate cancer target genes (Hes6, Sox9, Jmjd1a); this Siah2-HIF-1α/FoxA2 axis regulates neuroendocrine tumor formation. Co-immunoprecipitation of HIF-1α with FoxA2; gene expression analysis; Siah2 inhibition experiments (review/perspective summarizing experimental findings from cited primary work) Oncotarget Low 21037926
2014 Foxa1 and Foxa2 control glucagon gene expression through the G2 element in pancreatic alpha cells; Foxa2 (but not Foxa1) regulates MafB, Pou3f4, Pcsk2, Nkx2.2, Kir6.2, and Sur1 gene expression; combined Foxa1/Foxa2 loss affects glucagon secretion; Foxa2 directly binds the promoters of Nkx2.2, Kir6.2, Sur1, Gipr, Isl1, and Pou3f4 genes. siRNA knockdown of Foxa1/Foxa2 in primary rat alpha cells and alpha-cell lines; ChIP for Foxa2 at target gene promoters; glucagon secretion assays Endocrinology Medium 25057789

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes. Nature 338 15616563
2012 Foxa1 and Foxa2 are essential for sexual dimorphism in liver cancer. Cell 325 22265403
2007 MicroRNA-124a regulates Foxa2 expression and intracellular signaling in pancreatic beta-cell lines. The Journal of biological chemistry 275 17462994
2007 Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner. Development (Cambridge, England) 236 17596284
2004 Foxa2 regulates alveolarization and goblet cell hyperplasia. Development (Cambridge, England) 227 14757645
2005 Compensatory roles of Foxa1 and Foxa2 during lung morphogenesis. The Journal of biological chemistry 224 15668254
2010 Foxa2 is essential for mouse endometrial gland development and fertility. Biology of reproduction 186 20484741
2004 Immunohistochemical localization of Foxa1 and Foxa2 in mouse embryos and adult tissues. Gene expression patterns : GEP 186 15567715
2012 Foxa2 and H2A.Z mediate nucleosome depletion during embryonic stem cell differentiation. Cell 169 23260146
2009 Foxa2 regulates polarity and epithelialization in the endoderm germ layer of the mouse embryo. Development (Cambridge, England) 167 19234065
2005 Foxa2 integrates the transcriptional response of the hepatocyte to fasting. Cell metabolism 152 16098831
2017 Forkhead box a2 (FOXA2) is essential for uterine function and fertility. Proceedings of the National Academy of Sciences of the United States of America 147 28049832
2004 Foxa2 regulates multiple pathways of insulin secretion. The Journal of clinical investigation 145 15314688
2009 Foxa1 and Foxa2 control the differentiation of goblet and enteroendocrine L- and D-cells in mice. Gastroenterology 131 19737569
2022 FOXA2 drives lineage plasticity and KIT pathway activation in neuroendocrine prostate cancer. Cancer cell 129 36332622
2019 FOXA2 Is Required for Enhancer Priming during Pancreatic Differentiation. Cell reports 121 31291575
2009 Foxa1 and Foxa2 function both upstream of and cooperatively with Lmx1a and Lmx1b in a feedforward loop promoting mesodiencephalic dopaminergic neuron development. Developmental biology 116 19607821
2009 Foxa1 and Foxa2 regulate bile duct development in mice. The Journal of clinical investigation 114 19436110
2004 Foxa2 is required for transition to air breathing at birth. Proceedings of the National Academy of Sciences of the United States of America 108 15452354
2010 Foxa1 and Foxa2 maintain the metabolic and secretory features of the mature beta-cell. Molecular endocrinology (Baltimore, Md.) 98 20534694
2014 Hippo signaling influences HNF4A and FOXA2 enhancer switching during hepatocyte differentiation. Cell reports 94 25263553
2013 Glucagon-induced acetylation of Foxa2 regulates hepatic lipid metabolism. Cell metabolism 93 23416070
2017 FOXA2 is a sensitive and specific marker for small cell neuroendocrine carcinoma of the prostate. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 91 28621319
2015 Foxa2 and Cdx2 cooperate with Nkx2-1 to inhibit lung adenocarcinoma metastasis. Genes & development 85 26341558
2015 Lhx1 functions together with Otx2, Foxa2, and Ldb1 to govern anterior mesendoderm, node, and midline development. Genes & development 84 26494787
2018 miR-590-3p Promotes Ovarian Cancer Growth and Metastasis via a Novel FOXA2-Versican Pathway. Cancer research 80 29748371
2011 IKKα activation of NOTCH links tumorigenesis via FOXA2 suppression. Molecular cell 80 22196886
2010 Foxa2 and Nurr1 synergistically yield A9 nigral dopamine neurons exhibiting improved differentiation, function, and cell survival. Stem cells (Dayton, Ohio) 80 20049900
2005 Foxa1 and Foxa2 interact with the androgen receptor to regulate prostate and epididymal genes differentially. Annals of the New York Academy of Sciences 80 16467259
2015 Combined Nurr1 and Foxa2 roles in the therapy of Parkinson's disease. EMBO molecular medicine 79 25759364
2015 Insm1 cooperates with Neurod1 and Foxa2 to maintain mature pancreatic β-cell function. The EMBO journal 79 25828096
2022 Ginger nanoparticles mediated induction of Foxa2 prevents high-fat diet-induced insulin resistance. Theranostics 78 35154496
2014 Hedgehog signaling regulates FOXA2 in esophageal embryogenesis and Barrett's metaplasia. The Journal of clinical investigation 77 25083987
2010 Foxa2 programs Th2 cell-mediated innate immunity in the developing lung. Journal of immunology (Baltimore, Md. : 1950) 77 20483781
2007 Foxa2 controls vesicle docking and insulin secretion in mature Beta cells. Cell metabolism 75 17908556
2017 Foxa2 identifies a cardiac progenitor population with ventricular differentiation potential. Nature communications 73 28195173
2009 Distinct roles of FOXA2 and FOXA3 in allergic airway disease and asthma. American journal of respiratory and critical care medicine 72 19628779
2014 Transcription factors Foxa1 and Foxa2 are required for adult dopamine neurons maintenance. Frontiers in cellular neuroscience 71 25249938
2021 The circRNA CNEACR regulates necroptosis of cardiomyocytes through Foxa2 suppression. Cell death and differentiation 70 34588633
2017 Foxa2 and Pdx1 cooperatively regulate postnatal maturation of pancreatic β-cells. Molecular metabolism 69 28580283
2019 Pre-marked chromatin and transcription factor co-binding shape the pioneering activity of Foxa2. Nucleic acids research 68 31350899
2018 FoxA1 and FoxA2 drive gastric differentiation and suppress squamous identity in NKX2-1-negative lung cancer. eLife 66 30475207
2005 Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphé neurones and cranial motoneurones. Development (Cambridge, England) 66 15677724
2013 Hippo-Foxa2 signaling pathway plays a role in peripheral lung maturation and surfactant homeostasis. Proceedings of the National Academy of Sciences of the United States of America 65 23620511
2023 FOXA2 Suppression by TRIM36 Exerts Anti-Tumor Role in Colorectal Cancer Via Inducing NRF2/GPX4-Regulated Ferroptosis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 62 37875418
2017 Novel FOXA2 mutation causes Hyperinsulinism, Hypopituitarism with Craniofacial and Endoderm-derived organ abnormalities. Human molecular genetics 60 28973288
2009 Molecular interactions between HNF4a, FOXA2 and GABP identified at regulatory DNA elements through ChIP-sequencing. Nucleic acids research 58 19822575
2014 Thioredoxin-interacting protein promotes islet amyloid polypeptide expression through miR-124a and FoxA2. The Journal of biological chemistry 57 24627476
2024 FOXA1 and FOXA2: the regulatory mechanisms and therapeutic implications in cancer. Cell death discovery 55 38605023
2020 Histone demethylase PHF8 drives neuroendocrine prostate cancer progression by epigenetically upregulating FOXA2. The Journal of pathology 52 33009820
2010 Foxa1 and Foxa2 positively and negatively regulate Shh signalling to specify ventral midbrain progenitor identity. Mechanisms of development 52 21093585
2018 The nuclear bile acid receptor FXR is a PKA- and FOXA2-sensitive activator of fasting hepatic gluconeogenesis. Journal of hepatology 51 29981427
2022 A FoxA2+ long-term stem cell population is necessary for growth plate cartilage regeneration after injury. Nature communications 48 35523895
2020 Selective inhibition of stemness through EGFR/FOXA2/SOX9 axis reduces pancreatic cancer metastasis. Oncogene 48 33288882
2016 Transcriptomic and CRISPR/Cas9 technologies reveal FOXA2 as a tumor suppressor gene in pancreatic cancer. American journal of physiology. Gastrointestinal and liver physiology 48 27151939
2014 Foxa1 and Foxa2 regulate α-cell differentiation, glucagon biosynthesis, and secretion. Endocrinology 48 25057789
2012 β-Catenin signaling regulates Foxa2 expression during endometrial hyperplasia formation. Oncogene 45 22945641
2022 FoxA1 and FoxA2 control growth and cellular identity in NKX2-1-positive lung adenocarcinoma. Developmental cell 43 35835117
2019 The Club Cell Marker SCGB1A1 Downstream of FOXA2 is Reduced in Asthma. American journal of respiratory cell and molecular biology 42 30576223
2014 Foxa2 acts as a co-activator potentiating expression of the Nurr1-induced DA phenotype via epigenetic regulation. Development (Cambridge, England) 42 24496614
2013 SIRT1 deacetylates FOXA2 and is critical for Pdx1 transcription and β-cell formation. International journal of biological sciences 42 24163589
2019 FOXA2 controls the cis-regulatory networks of pancreatic cancer cells in a differentiation grade-specific manner. The EMBO journal 41 31531882
2017 Structure of the Forkhead Domain of FOXA2 Bound to a Complete DNA Consensus Site. Biochemistry 39 28644006
2020 LncRNA FTX activates FOXA2 expression to inhibit non-small-cell lung cancer proliferation and metastasis. Journal of cellular and molecular medicine 38 32176463
2018 FOXA2 promotes the proliferation, migration and invasion, and epithelial mesenchymal transition in colon cancer. Experimental and therapeutic medicine 38 29896233
2017 Aberrant DNA methylation and expression of SPDEF and FOXA2 in airway epithelium of patients with COPD. Clinical epigenetics 38 28450970
2017 FOXA2 alleviates CCl4-induced liver fibrosis by protecting hepatocytes in mice. Scientific reports 38 29138513
2020 Embryonic liver developmental trajectory revealed by single-cell RNA sequencing in the Foxa2eGFP mouse. Communications biology 37 33144666
2016 MicroRNA-1291 targets the FOXA2-AGR2 pathway to suppress pancreatic cancer cell proliferation and tumorigenesis. Oncotarget 37 27322206
2021 The pioneer and differentiation factor FOXA2 is a key driver of yolk-sac tumour formation and a new biomarker for paediatric and adult yolk-sac tumours. Journal of cellular and molecular medicine 36 33448076
2015 Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord. PLoS genetics 36 26684323
2020 Inactivation of FOXA2 by Respiratory Bacterial Pathogens and Dysregulation of Pulmonary Mucus Homeostasis. Frontiers in immunology 34 32269574
2013 Neurogenin3 cooperates with Foxa2 to autoactivate its own expression. The Journal of biological chemistry 34 23471965
2024 FOXA2 rewires AP-1 for transcriptional reprogramming and lineage plasticity in prostate cancer. Nature communications 32 38851846
2018 Congenital Hyperinsulinism and Hypopituitarism Attributable to a Mutation in FOXA2. The Journal of clinical endocrinology and metabolism 31 29329447
2010 The Siah2-HIF-FoxA2 axis in prostate cancer – new markers and therapeutic opportunities. Oncotarget 30 21037926
2017 MicroRNA-200a inhibits cell growth and metastasis by targeting Foxa2 in hepatocellular carcinoma. Journal of Cancer 29 28367241
2022 CD44 Promotes Breast Cancer Metastasis through AKT-Mediated Downregulation of Nuclear FOXA2. Biomedicines 28 36289750
2020 Exendin-4 restores airway mucus homeostasis through the GLP1R-PKA-PPARγ-FOXA2-phosphatase signaling. Mucosal immunology 28 32034274
2020 FoxA2 inhibits the proliferation of hepatic progenitor cells by reducing PI3K/Akt/HK2-mediated glycolysis. Journal of cellular physiology 28 32495363
2019 The long noncoding RNA Falcor regulates Foxa2 expression to maintain lung epithelial homeostasis and promote regeneration. Genes & development 28 30923168
2017 The FOXA2 transcription factor is frequently somatically mutated in uterine carcinosarcomas and carcinomas. Cancer 28 28940304
2011 Dynamic regulation of PDX-1 and FoxO1 expression by FoxA2 in dexamethasone-induced pancreatic β-cells dysfunction. Endocrinology 28 21385937
2009 Foxa2-dependent hepatic gene regulatory networks depend on physiological state. Physiological genomics 27 19417011
2012 GATA6 and FOXA2 regulate Wnt6 expression during extraembryonic endoderm formation. Stem cells and development 26 22607194
2023 Gambogenic acid inhibits proliferation and ferroptosis by targeting the miR-1291/FOXA2 and AMPKα/SLC7A11/GPX4 axis in colorectal cancer. Cell biology international 25 37471707
2021 MRE11 promotes oral cancer progression through RUNX2/CXCR4/AKT/FOXA2 signaling in a nuclease-independent manner. Oncogene 25 33927349
2017 MicroRNA-187 promotes growth and metastasis of gastric cancer by inhibiting FOXA2. Oncology reports 25 28098868
2014 Developmental lung expression and transcriptional regulation of claudin-6 by TTF-1, Gata-6, and FoxA2. Respiratory research 25 24970044
2022 FOXA2 suppresses endometrial carcinogenesis and epithelial-mesenchymal transition by regulating enhancer activity. The Journal of clinical investigation 24 35703180
2014 SIRT1 mediates FOXA2 breakdown by deacetylation in a nutrient-dependent manner. PloS one 24 24875183
2015 Expression and Regulation of Transcription Factor FoxA2 in Chronic Rhinosinusitis With and Without Nasal Polyps. Allergy, asthma & immunology research 23 25749777
2012 Foxa2 may modulate hepatic apoptosis through the cIAP1 pathway. Cellular signalling 23 23275033
2023 Yap controls notochord formation and neural tube patterning by integrating mechanotransduction with FoxA2 and Shh expression. Science advances 22 37315133
2023 FoxA2 is a reliable marker for the diagnosis of yolk sac tumour postpubertal-type. Histopathology 22 37317674
2022 TET1 dioxygenase is required for FOXA2-associated chromatin remodeling in pancreatic beta-cell differentiation. Nature communications 22 35798741
2021 Aberrant development of pancreatic beta cells derived from human iPSCs with FOXA2 deficiency. Cell death & disease 21 33473118
2019 MiR-942 regulates the function of breast cancer cell by targeting FOXA2. Bioscience reports 21 31701999
2016 Meta-Analysis of Transcriptome Data Related to Hippocampus Biopsies and iPSC-Derived Neuronal Cells from Alzheimer's Disease Patients Reveals an Association with FOXA1 and FOXA2 Gene Regulatory Networks. Journal of Alzheimer's disease : JAD 21 26890743
2012 Forkhead box protein A2 (FOXA2) protein stability and activity are regulated by sumoylation. PloS one 21 23118920

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