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Showing ZFPM2 — FOG2 is a alias.

ZFPM2

Zinc finger protein ZFPM2 · UniProt Q8WW38

Length
1151 aa
Mass
128.2 kDa
Annotated
2026-06-11
100 papers in source corpus 33 papers cited in narrative 31 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

ZFPM2/FOG-2 is a multi-zinc-finger nuclear transcriptional co-regulator that controls organ development and adult tissue homeostasis primarily by binding GATA transcription factors and modulating their activity in a promoter- and cell-type-dependent manner (PMID:9927675, PMID:10330188, PMID:9927674, PMID:10801815, PMID:14613857). It associates through zinc fingers 1 and 6 with conserved motifs in the N-terminal zinc finger of GATA-4, with an N-terminal domain (aa 1–247) both necessary and sufficient for repression and a defined nuclear localization signal directing nuclear targeting (PMID:10801815). FOG-2 represses GATA-dependent transcription by recruiting co-repressor machinery — CtBP via a conserved PIDLS motif (required in some lineages but dispensable for cardiac GATA4 repression) and the NuRD nucleosome remodeling/deacetylase complex, the latter being required in cardiomyocytes for proliferation through repression of the cell-cycle inhibitor Cdkn1a/p21 (PMID:10438528, PMID:10801815, PMID:11404479, PMID:25196150); it can also antagonize GATA4 coactivation by competing with p300 (PMID:15220332). Its repressive output is tuned by SUMOylation, which attenuates GATA-4 interaction and repression, and its abundance is set post-transcriptionally by 3′UTR-targeting microRNAs including miR-130a and the miR-17-92 cluster (PMID:23226341, PMID:19582148, PMID:22267003). In the heart, FOG-2 function in myocardium is required for ventricular development, cardiac septation/looping, and coronary vessel formation, and in the adult it antagonizes a TBX5/GATA4 atrial gene regulatory network — including at a SERCA2/Atp2a2 enhancer — to maintain normal atrial rhythm (PMID:10892744, PMID:10888889, PMID:19411759, PMID:38189150). In gonadal somatic cells the GATA4–FOG2 interaction is required for Sry induction and male sex determination, with human FOG2 coding mutations that disrupt GATA4 binding causing 46,XY gonadal dysgenesis, and FOG-2 is also required for normal diaphragm and lung development, with a human loss-of-function allele linked to pulmonary hypoplasia (PMID:12223418, PMID:24549039, PMID:16103912). Beyond transcription, FOG-2 directly inhibits PI3K by binding the p85α regulatory subunit, a conserved mechanism that restrains cell growth and influences hepatic insulin sensitivity via PPARα (PMID:20005803, PMID:23788640, PMID:27207553).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1999 High

    Established the founding molecular activity — that ZFPM2 is a nuclear zinc-finger protein that physically engages GATA-4 and represses GATA-dependent cardiac transcription, defining it as a GATA co-regulator.

    Evidence Co-IP, GST pulldown and reporter assays in cardiomyocytes, replicated across three simultaneous papers

    PMID:10330188 PMID:9927674 PMID:9927675

    Open questions at the time
    • Did not resolve which zinc fingers mediate binding
    • Did not identify the co-repressor machinery responsible for repression
  2. 1999 High

    Identified a CtBP co-repressor recruitment mechanism via the PIDLS motif and showed it is context-dependent, distinguishing lineage-specific from cardiac repression modes.

    Evidence GST pulldown, reporter assays and PIDLS motif mutagenesis

    PMID:10438528 PMID:10801815 PMID:11404479

    Open questions at the time
    • Did not explain what co-repressor substitutes for CtBP in cardiac GATA4 repression
  3. 2000 High

    Mapped the interaction and repression determinants, showing zinc fingers 1 and 6 bind the GATA N-terminal zinc finger and that the N-terminal domain alone is sufficient to repress, providing the structural logic of GATA engagement.

    Evidence Deletion and site-directed mutagenesis, GST pulldown, reporter assays

    PMID:10801815

    Open questions at the time
    • No crystal/structural model of the FOG2–GATA interface
    • Did not define the effector domain mechanism of N-terminal repression
  4. 2000 High

    Demonstrated in vivo requirement in heart morphogenesis, with cardiomyocyte-specific rescue proving myocardial FOG-2 is necessary and sufficient for coronary vessel development and required for septation and looping.

    Evidence Germline knockout and cardiomyocyte transgenic rescue in mice; independent targeted-KO study

    PMID:10888889 PMID:10892744

    Open questions at the time
    • Did not identify the transcriptional targets driving coronary angiogenesis
    • Did not separate GATA-dependent from GATA-independent roles in vivo
  5. 2002 High

    Placed FOG2 in sex determination, showing the GATA4–FOG2 interaction is required for Sry induction and the male program, establishing a developmental pathway position via two genetic models.

    Evidence Fog2-null and Gata4 interaction-deficient knockin mice with RT-PCR and in situ hybridization

    PMID:12223418

    Open questions at the time
    • Did not identify direct GATA4-FOG2 target genes upstream of Sry
    • Did not address human relevance at this stage
  6. 2002 Medium

    Extended FOG2 repression to additional GATA-driven gonadal promoters and identified retinoid- and lineage-specific modulation, refining the context-dependent nature of its regulatory output.

    Evidence Transfection reporter assays across MIS/inhibin/aromatase/StAR promoters; RXRα ligand-dependent interaction assays

    PMID:12239108 PMID:12480945 PMID:12606418

    Open questions at the time
    • Largely transfection-based without in vivo confirmation of each promoter
    • Direct chromatin occupancy not demonstrated
  7. 2003 Medium

    Showed FOG-2 can switch from repressor to activator depending on cell type, revealing bidirectional modulation of GATA activity at the Kv4.2 locus.

    Evidence Kv4.2 promoter reporter assays with FOG-binding-deficient GATA mutants in cardiac myocytes versus PC12 cells

    PMID:14613857

    Open questions at the time
    • GATA-independent activation mechanism in PC12 cells not defined
    • No in vivo validation
  8. 2004 High

    Defined a coactivator-competition mechanism, showing FOG-2 competes with GATA-4 for p300 and represses cardiac hypertrophic responses, linking it to stress signaling.

    Evidence Reciprocal co-IP and reporter assays with phenylephrine-induced hypertrophy in cardiomyocytes

    PMID:15220332

    Open questions at the time
    • Relative contribution of p300 competition versus NuRD/CtBP recruitment unresolved
    • No in vivo hypertrophy model
  9. 2005 High

    Extended in vivo requirement to diaphragm and lung development and provided the first human loss-of-function evidence, linking FOG2 to pulmonary hypoplasia.

    Evidence ENU splice mutant mouse plus human autopsy case sequencing

    PMID:16103912

    Open questions at the time
    • Did not identify the GATA partner or targets in diaphragm/lung progenitors
    • Single human case
  10. 2009 High

    Uncovered a transcription-independent function — direct inhibition of PI3K by binding p85α — establishing FOG2 as a growth suppressor conserved from fly to human.

    Evidence Reciprocal co-IP, cell growth assays, and genetic epistasis in Drosophila and human cells

    PMID:20005803

    Open questions at the time
    • Did not define the FOG2 region binding p85α
    • Relationship between nuclear and cytoplasmic FOG2 pools unresolved
  11. 2009 High

    Dissected temporal requirements in heart and identified post-transcriptional control by miR-130a, showing FOG-2 is required in adult myocardium and that microRNA-driven FOG-2 loss phenocopies genetic deficiency.

    Evidence Conditional/inducible Fog2 knockouts; 3′UTR reporter, miR-130a knockdown and transgenic overexpression

    PMID:19411759 PMID:19578715 PMID:19582148

    Open questions at the time
    • Full angiogenic target set not enumerated
    • Tnnt1 target shown only at expression level without chromatin analysis
  12. 2008 High

    Linked FOG-2 to cardiac calcium handling and disease, showing it interacts with TRα1 to suppress SERCA2 and is upregulated in failing hearts with overexpression causing dysfunction.

    Evidence Co-IP, transgenic overexpression, SERCA2 promoter reporter and T3 experiments

    PMID:18658259

    Open questions at the time
    • Direct chromatin occupancy at SERCA2 not shown at this stage
    • Cause of FOG-2 upregulation in failure undefined
  13. 2014 High

    Identified NuRD recruitment as the in vivo repression mechanism driving cardiomyocyte proliferation via Cdkn1a/p21, with genetic rescue proving the target relationship.

    Evidence NuRD-binding knock-in mouse (R3K5A), proliferation assays, Cdkn1a reporter, and Fog2(R3K5A);Cdkn1a-/- rescue

    PMID:25196150

    Open questions at the time
    • How NuRD recruitment integrates with CtBP and p300 mechanisms unclear
    • Other NuRD-dependent targets not mapped
  14. 2012 High

    Established SUMOylation and additional microRNAs as layers tuning FOG-2 abundance and activity, with SUMOylation attenuating GATA-4 interaction and repression.

    Evidence SUMO-site mutagenesis, SENP de-SUMOylation, reporter assays and co-IP; miR-17-92 3′UTR reporter and rescue

    PMID:22267003 PMID:23226341

    Open questions at the time
    • In vivo physiological role of FOG-2 SUMOylation not tested
    • Upstream signals controlling FOG-2 SUMOylation unknown
  15. 2013 High

    Connected FOG2 PI3K inhibition to disease physiology, showing TGF-β/miR-200b/c suppression of FOG2 drives Akt/ERK activation and mesangial hypertrophy.

    Evidence siRNA knockdown, miR-200b/c mimic/inhibitor, and pathway western blots in mesangial cells

    PMID:23788640

    Open questions at the time
    • In vivo renal validation not performed
    • Whether nuclear FOG2 functions contribute not addressed
  16. 2014 Medium

    Extended FOG2 partnerships beyond GATA4 to AML1 (in a leukemic fusion) and to the co-repressor Art27 and NKX2.5, broadening its co-regulatory network.

    Evidence Fusion gene characterization with co-IP/reporter assays; yeast two-hybrid validated by co-IP and reporters

    PMID:15705784 PMID:24743694

    Open questions at the time
    • AML1-FOG2 is a disease-specific fusion, not endogenous FOG2 function
    • Art27 interaction lacks in vivo validation
  17. 2011 High

    Refined gonadal roles by conditional ablation, revealing non-overlapping essential functions for FOG2 and GATA4 in testis development with FOG2 loss causing sex reversal.

    Evidence Sf1Cre conditional knockouts with gonadal gene expression and histology

    PMID:21385577

    Open questions at the time
    • Mechanistic basis of FOG2-specific male-pathway block not fully defined
  18. 2008 High

    Identified GATA4-FOG2 repression of Dkk1 and β-catenin signaling as a node in ovarian versus testis fate, deepening the developmental logic of sex determination.

    Evidence Double-mutant genetic epistasis (Fog2/Dkk1, Gata4ki/Dkk1) and gonadal β-catenin conditional KO

    PMID:18927154

    Open questions at the time
    • Direct chromatin binding of GATA4-FOG2 at Dkk1 not shown
  19. 2016 High

    Broadened FOG2 function to neocortical neuron differentiation and hepatic metabolism, showing it controls corticothalamic projection neuron identity via Ctip2 and regulates insulin sensitivity and hepatic triglyceride through PPARα.

    Evidence Conditional CThPN knockout with axonal tracing; adenoviral and liver-specific KO models with PPARα rescue

    PMID:27207553 PMID:27321927

    Open questions at the time
    • Whether neuronal/hepatic roles depend on GATA partners or PI3K inhibition unresolved
    • Transcriptional targets in liver beyond PPARα undefined
  20. 2024 High

    Defined the genomic mechanism of adult atrial rhythm control, showing FOG2 antagonizes a TBX5/GATA4 atrial network at co-bound loci including a SERCA2 enhancer, with genetic epistasis rescuing TBX5-driven arrhythmia.

    Evidence Transgenic overexpression, in vivo/cellular electrophysiology, calcium imaging, ChIP/genomic analysis, and Tbx5+/-;Zfpm2+/- epistasis

    PMID:38189150

    Open questions at the time
    • Full TBX5/GATA4 co-regulated atrial target set not exhaustively defined
    • Cause of FOG2 upregulation in human heart failure unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FOG2 integrates its distinct molecular modes — GATA co-repression via NuRD/CtBP, coactivator competition, SUMO-tuned activity, and cytoplasmic PI3K inhibition — into tissue-specific outputs remains unresolved.
  • No structural model of FOG2 in any complex
  • Spatial control distinguishing nuclear transcriptional from cytoplasmic PI3K functions not established
  • Genome-wide direct target catalogs across tissues incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0060090 molecular adaptor activity 3 GO:0003677 DNA binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 2 R-HSA-4839726 Chromatin organization 2
Partners
CTBP2GATA4NKX2-5P300PIK3R1RXRATBX5THRA
Complex memberships
NuRD complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 FOG-2 (ZFPM2) is a nuclear protein containing eight zinc finger motifs that physically associates with the N-terminal zinc finger of GATA-4 both in vitro and in vivo, and overexpression of FOG-2 represses GATA-4-dependent transcription from multiple cardiac-restricted promoters in NIH 3T3 cells and primary rat cardiomyocytes. Co-immunoprecipitation, GST pulldown, co-transfection reporter assays in cardiomyocytes Proceedings of the National Academy of Sciences of the United States of America High 10330188 9927674 9927675
1999 FOG-2 interacts with the co-repressor C-terminal binding protein-2 (CtBP2) via a conserved PIDLS motif, and this interaction is required for repression activity in some contexts (repression of crystal cell production in Drosophila) but is NOT required for FOG-2-mediated repression of GATA4-dependent transcription in mammalian cells. GST pulldown, co-transfection luciferase reporter assays, site-directed mutagenesis of PIDLS motif The Journal of biological chemistry High 10438528 10801815 11404479
2000 FOG-2 knockout mice die at midgestation with thin ventricular myocardium, common atrioventricular canal, tetralogy of Fallot malformation, and complete absence of coronary vasculature despite an intact epicardial layer. Transgenic re-expression of FOG-2 specifically in cardiomyocytes rescues the coronary vascular phenotype, demonstrating that FOG-2 function in myocardium is required and sufficient for coronary vessel development. Germline knockout mouse, transgenic rescue with cardiomyocyte-specific re-expression, histology, ICAM-2/FLK-1 marker analysis Cell High 10892744
2000 FOG-2 (Zfpm2) deficiency in mice produces a syndrome of tricuspid atresia including absent tricuspid valve, large atrial septal defect, ventricular septal defect, elongated left ventricular outflow tract, and hypoplasia of the compact zone of the left ventricle, establishing Zfpm2 as required for normal cardiac looping and septation. Targeted mutagenesis (gene knockout), histological and morphological analysis of embryos Nature genetics High 10888889
2000 A conserved N-terminal domain of FOG-2 (amino acids 1–247) is both necessary and sufficient to repress GATA4-dependent transcription, independent of CtBP2 interaction. Zinc fingers 1 and 6 of FOG-2 each interact with evolutionarily conserved motifs in the N-terminal zinc finger of GATA proteins. A nuclear localization signal (RKRRK, aa 736–740) is required for nuclear targeting of FOG-2. Deletion mutagenesis, co-transfection reporter assays, GST pulldown with GATA protein fragments, site-directed mutagenesis The Journal of biological chemistry High 10801815
2002 GATA4 and FOG2 physical interaction is required for normal gonadal differentiation and Sry expression. XY mice homozygous for Fog2 null or a Gata4 knockin that abrogates FOG co-factor binding show severely reduced Sry transcript levels at E11.5, loss of Sox9/Mis/Dhh expression, and ectopic Wnt4 expression, while Wt1 and Sf1 are unaffected. Genetic epistasis using Fog2-null and Gata4(ki/ki) mouse models, quantitative RT-PCR, in situ hybridization Development (Cambridge, England) High 12223418
2001 FOG-2 represses crystal cell production in Drosophila, but a FOG-2 mutant lacking the conserved CtBP-binding motif (PIDLS) fails to repress crystal cell lineage, indicating that CtBP recruitment is required for FOG-2 function in blood but not in cardiac or eye contexts, revealing context-dependent repression mechanisms. Transgenic Drosophila overexpression, CtBP-binding mutant analysis, cell lineage counting Proceedings of the National Academy of Sciences of the United States of America Medium 11404479
2002 FOG-2 represses GATA-4-mediated transactivation of the Müllerian-inhibiting substance (MIS) gene in granulosa cells, and its loss of expression in fetal Sertoli cells accompanies testicular cord formation, suggesting a role in suppressing MIS in the developing ovary. In vitro transfection reporter assays in granulosa cells, Northern blot, RNA in situ hybridization, immunohistochemistry Biology of reproduction Medium 12606418
2002 FOG-1 and FOG-2 differentially repress GATA-dependent promoter activities of multiple gonadal genes (MIS, inhibin alpha, P450 aromatase, StAR) in testicular cells in a promoter- and cell-type-dependent manner. Co-transfection luciferase reporter assays in testicular cell lines Endocrinology Medium 12239108
2002 Liganded RXRα interacts directly with GATA-4 (via its DNA-binding domain to the second zinc finger of GATA-4) and with FOG-2 in a 9-cis-RA-dependent manner. Co-expression of liganded RXRα and FOG-2 results in additive repression of GATA-4 activity in ventricular myocytes, revealing a retinoid-dependent mechanism linking RXRα to the FOG-2 co-repressor complex. GST pulldown, co-transfection reporter assays in cardiomyocytes, ligand-dependent interaction assays The Journal of biological chemistry Medium 12480945
2003 FOG-2 regulates Kv4.2 potassium channel gene transcription by differentially modulating GATA-dependent activation: in cardiac myocytes FOG-2 suppresses GATA-induced transcription through a GATA-FOG complex, whereas in PC12 cells FOG-2 enhances GATA activity through a GATA-independent mechanism. Transient transfection with Kv4.2 promoter-luciferase reporters, use of GATA mutants unable to bind FOG, in cardiac myocytes and PC12 cells Cardiovascular research Medium 14613857
2004 FOG-2 physically interacts with the transcriptional coactivator p300, competes with GATA-4 for p300 binding, reduces the GATA-4/p300 interaction, and represses phenylephrine-induced hypertrophic responses (myofibrillar organization, cell size increase, hypertrophy-associated gene transcription) in cardiac myocytes. In COS7 cells with disrupted endogenous p300, FOG-2 cannot repress baseline GATA-4 activity but can repress p300-mediated GATA-4 enhancement. Co-immunoprecipitation/western blot, co-transfection reporter assays, phenylephrine-induced hypertrophy model in cardiomyocytes The Journal of biological chemistry High 15220332
2005 Fog2 (Zfpm2) is required for normal diaphragm and lung development; an ENU-induced splice donor mutation in mice produces pulmonary hypoplasia and abnormal diaphragmatic development, and a de novo FOG2 premature stop codon was identified in a human infant with severe bilateral pulmonary hypoplasia and abnormally muscularized diaphragm. ENU mutagenesis screen in mice, DNA sequencing of splice site and coding sequence, human autopsy case sequencing PLoS genetics High 16103912
2006 FOG-2 attenuates endothelial-to-mesenchymal transformation (EMT) in developing endocardial cushions; FOG-2-deficient mice show a 78% increase in outflow tract cushion EMT and 35% increase in atrioventricular cushion EMT in collagen gel invasion assays, without differences in mesenchymal cell proliferation, differentiation, apoptosis, or myocardialization. FOG-2 knockout mouse model, collagen gel invasion assay for EMT, proliferation/apoptosis/differentiation assays Developmental biology High 17274974
2007 Loss of the FOG-2–GATA4 interaction (via Gata4(ki/ki) or Fog2(-/-)) results in the absence of ovarian development and identifies Dkk1 (a secreted inhibitor of canonical β-catenin signaling) as a target of GATA4-FOG2 repression. Ablation of β-catenin in gonads disrupts female development, and double mutants Gata4(ki/ki);Dkk1(-/-) or Fog2(-/-);Dkk1(-/-) show partial restoration of normal ovarian gene expression. Genetic epistasis with double mutants (Fog2/Dkk1 and Gata4(ki)/Dkk1), gonad-specific β-catenin conditional knockout, gene expression analysis Development (Cambridge, England) High 18927154
2008 FOG-2 physically interacts with thyroid hormone receptor-alpha1 (TRα1) and abrogates T3-mediated SERCA2 gene promoter activation. FOG-2 is upregulated in human and murine failing hearts; cardiac-specific FOG-2 overexpression in transgenic mice causes depressed cardiac function, activation of the fetal gene program, and reduced SERCA2 transcript and protein levels. Co-immunoprecipitation, transgenic mouse overexpression, SERCA2 promoter-reporter assays, T3-treatment experiments in cardiomyocytes Circulation research High 18658259
2009 FOG-2 expression in cardiomyocytes is post-transcriptionally regulated by microRNA-130a, which binds a conserved site in the FOG-2 3′ UTR. Cardiomyocyte-specific transgenic overexpression of miR-130a reduces FOG-2 protein by up to 80% and causes ventricular wall hypoplasia and ventricular septal defects resembling FOG-2 deficiency. Luciferase 3′ UTR reporter assay, miR-130a knockdown in fibroblasts, transgenic mouse overexpression of miR-130a, western blot PloS one High 19582148
2009 FOG-2 and its target USH (Drosophila) inhibit PI3K activity by directly binding to p85α, the regulatory subunit of PI3K, interfering with PI3K complex formation, thereby suppressing cell growth. This mechanism is conserved: human FOG2 also binds p85α and suppresses PI3K-dependent growth. Co-immunoprecipitation of FOG2 with p85α, cell growth assays, genetic epistasis in Drosophila fat body and human cells Cell High 20005803
2009 Early cardiomyocyte-restricted loss of Fog2 recapitulates cardiac and coronary defects of germline knockouts. Later cardiomyocyte-restricted Fog2 loss (Fog2MC) causes severely depressed ventricular function and death at 8–14 weeks with paucity of coronary vessels, myocardial hypoxia, cardiomyocyte apoptosis, and cardiac fibrosis. Ablation of the FOG2–GATA4 interaction produces similar adult phenotypes, and loss of FOG2 or FOG2–GATA4 interaction alters expression of angiogenesis-related genes. Spatiotemporally regulated conditional Fog2 knockout (Cre-lox), inducible adult-specific Fog2 deletion, Gata4 interaction-domain mutation, echocardiography, histology, gene expression The Journal of clinical investigation High 19411759
2009 Cardiac expression of slow skeletal troponin T (Tnnt1) strictly depends on physical interaction between GATA4 and FOG2 in the myocardium of both atria and ventricles, identifying Tnnt1 as a direct transcriptional target of the GATA4-FOG2 complex. Genetic analysis using Gata4(ki/ki) and Fog2(-/-) mouse models, gene expression analysis TheScientificWorldJournal Medium 19578715
2011 Conditional somatic ablation of Fog2 in gonadal cells causes an early partial block in the male pathway and sex reversal, while GATA4 loss primarily disrupts Dmrt1 expression and testis cord morphogenesis. These experiments reveal non-overlapping essential functions for GATA4 and FOG2 in testis development. Sf1Cre-mediated conditional knockout of Gata4 and Fog2, gonadal gene expression analysis, histology Developmental biology High 21385577
2012 The miR-17-5p and miR-20a members of the miR-17-92 cluster directly target sites in the FOG-2 3′ UTR and post-transcriptionally repress FOG-2 expression. Overexpression of miR-17-92 inhibits embryonic cardiomyocyte proliferation, an effect rescued by FOG-2 re-expression. Luciferase 3′ UTR reporter assay, RT-PCR, western blot, EdU proliferation assay with FOG-2 rescue in embryonic cardiomyocytes Brazilian journal of medical and biological research Medium 22267003
2012 FOG-2 is SUMOylated at four lysine residues (K324, K471, K915, K955). Mutation of SUMOylation sites or de-SUMOylation with SENP-1/SENP-8 results in stronger transcriptional repression activity. Increased SUMOylation (SUMO-1 overexpression or SUMO-1–FOG-2 fusion) abolishes repression of GATA-4-mediated BNP promoter activation. GATA-4 co-expression enhances FOG-2 SUMOylation, and a SUMO-deficient FOG-2 mutant shows increased interaction with GATA-4. Site-directed mutagenesis of SUMOylation sites, SENP-mediated de-SUMOylation, SUMO-1 overexpression, reporter assays, co-immunoprecipitation PloS one High 23226341
2013 TGF-β1 activates Akt in glomerular mesangial cells by inducing miR-200b/c, which targets FOG2 (an inhibitor of PI3K activation). FOG2 knockdown by siRNA activates both Akt and ERK through PI3K activation and increases protein content/cell ratio, mimicking hypertrophy. miR-200b/c inhibitors attenuate TGF-β-induced FOG2 decrease and mesangial hypertrophy. siRNA knockdown of FOG2, miR-200b/c mimic/inhibitor transfection, western blot for PI3K-Akt-ERK pathway, protein content assay in mesangial cells The Journal of biological chemistry High 23788640
2014 FOG-2 recruits the NuRD (Nucleosome Remodeling and Deacetylase) complex and this interaction is required in vivo for cardiomyocyte proliferation. Mice carrying an R3K5A mutation that disrupts NuRD binding show perinatal lethality, ventricular and atrial septal defects, thin ventricular myocardium, and 31% reduction in cardiomyocyte proliferation. The cell cycle inhibitor Cdkn1a (p21) is upregulated 2-fold, and genetic ablation of Cdkn1a partially rescues left ventricular wall thickness in FOG-2(R3K5A) mice. Knock-in mouse with NuRD-binding mutation (R3K5A), cardiomyocyte proliferation measurement, Cdkn1a promoter-reporter assay, double mutant rescue (Fog2(R3K5A);Cdkn1a-/-) Developmental biology High 25196150
2014 FOG-2 interacts with AML1 in the AML1-FOG2 fusion protein found in myelodysplasia with t(X;21). AML1-FOG2 represses transcriptional activity of both CBF and GATA1. AML1-FOG2 retains the CtBP-recruiting motif and associates with CtBP in a protein complex, implicating CtBP in AML1-FOG2-mediated transcriptional repression. Characterization of t(X;21) fusion gene, co-immunoprecipitation of AML1-FOG2 with CtBP, transcriptional reporter assays for CBF and GATA1 activity Blood Medium 15705784
2014 Art27 interacts physically with FOG-2, GATA-4, and NKX2.5 (identified by yeast two-hybrid and validated by co-immunoprecipitation) and functions as a co-repressor that down-regulates GATA-4/FOG-2 activity on cardiac-specific promoters (αMHC, ANP, BNP) in cardiomyocytes. Yeast two-hybrid library screen, co-immunoprecipitation, co-transfection luciferase reporter assays, microarray gene expression in cardiomyocytes PloS one Medium 24743694
2014 Two FOG2 missense mutations (p.S402R and p.R260Q/p.M544I) identified by whole exome sequencing in patients with 46,XY gonadal dysgenesis impair the ability of FOG2 protein to interact with GATA4, as demonstrated by functional interaction assays, providing the first evidence linking FOG2 coding mutations to 46,XY DSD in humans. Whole exome sequencing, protein-protein interaction functional assays (GST pulldown or equivalent), clinical genetics Human molecular genetics Medium 24549039
2016 FOG-2 (Fog2) controls corticothalamic projection neuron (CThPN) molecular differentiation, axonal targeting, and subtype diversity in the neocortex. Loss of Fog2 specifically disrupts differentiation of CThPN subsets specialized in motor function, in part by regulating the expression level of Ctip2 via combinatorial interactions with other molecular controls. Conditional knockout of Fog2 in CThPN, in situ hybridization, immunohistochemistry, axonal tracing, gene expression analysis Neuron Medium 27321927
2016 Hepatic FOG2 regulates insulin sensitivity and hepatic triglyceride accumulation through PPARα. FOG2 overexpression attenuates insulin signaling in hepatocytes; FOG2 knockdown ameliorates insulin resistance in db/db mice. FOG2 overexpression reduces hepatic TG accumulation via increased PPARα expression; re-expression of PPARα reverses the effects of FOG2 knockdown on insulin sensitivity and hepatic TG. FOG2 liver-specific knockout mice exhibit enhanced insulin sensitivity and elevated hepatic TG, both reversed by Ad-PPARα. Adenoviral FOG2 overexpression and shRNA knockdown in vivo and in vitro, liver-specific conditional knockout mouse, insulin tolerance tests, hepatic TG measurement, PPARα rescue experiments Diabetes High 27207553
2024 FOG2 is significantly upregulated in human atria during heart failure. Cardiomyocyte-specific FOG2 overexpression in mice causes primary spontaneous atrial fibrillation (before structural remodeling) by generating arrhythmia substrate including calcium cycling defects. FOG2 represses TBX5-dependent atrial gene expression by binding a subset of GATA4 and TBX5 co-bound genomic locations, including a conserved enhancer at the Atp2a2 (SERCA2) locus. Atrial rhythm abnormalities from Tbx5 haploinsufficiency are rescued by Zfpm2 haploinsufficiency, establishing FOG2 as antagonizing TBX5 in an atrial gene regulatory network. Cardiac-specific FOG2 transgenic overexpression, in vivo electrophysiology, cellular electrophysiology, calcium imaging, ChIP/genomic analysis of enhancer activity, genetic epistasis (Tbx5+/-;Zfpm2+/- double mutants), gene expression analysis Circulation High 38189150

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 fog-2, a germ-line-specific sex determination gene required for hermaphrodite spermatogenesis in Caenorhabditis elegans. Genetics 318 3396865
2000 FOG-2, a cofactor for GATA transcription factors, is essential for heart morphogenesis and development of coronary vessels from epicardium. Cell 317 10892744
2002 Gonadal differentiation, sex determination and normal Sry expression in mice require direct interaction between transcription partners GATA4 and FOG2. Development (Cambridge, England) 274 12223418
2009 Conserved MicroRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K. Cell 258 20005803
1999 Molecular cloning of FOG-2: a modulator of transcription factor GATA-4 in cardiomyocytes. Proceedings of the National Academy of Sciences of the United States of America 222 9927675
1999 FOG-2, a heart- and brain-enriched cofactor for GATA transcription factors. Molecular and cellular biology 178 10330188
2005 Fog2 is required for normal diaphragm and lung development in mice and humans. PLoS genetics 167 16103912
1999 FOG-2: A novel GATA-family cofactor related to multitype zinc-finger proteins Friend of GATA-1 and U-shaped. Proceedings of the National Academy of Sciences of the United States of America 162 9927674
2000 FOG-2, a novel F-box containing protein, associates with the GLD-1 RNA binding protein and directs male sex determination in the C. elegans hermaphrodite germline. Development (Cambridge, England) 136 11076749
2000 A syndrome of tricuspid atresia in mice with a targeted mutation of the gene encoding Fog-2. Nature genetics 135 10888889
2001 The Friend of GATA proteins U-shaped, FOG-1, and FOG-2 function as negative regulators of blood, heart, and eye development in Drosophila. Proceedings of the National Academy of Sciences of the United States of America 130 11404479
2000 Transcription factors GATA-4 and GATA-6 and a GATA family cofactor, FOG-2, are expressed in human ovary and sex cord-derived ovarian tumors. The Journal of clinical endocrinology and metabolism 103 10999851
2004 fog-2 and the evolution of self-fertile hermaphroditism in Caenorhabditis. PLoS biology 102 15630478
2000 A functionally conserved N-terminal domain of the friend of GATA-2 (FOG-2) protein represses GATA4-dependent transcription. The Journal of biological chemistry 101 10801815
2003 Mutations of ZFPM2/FOG2 gene in sporadic cases of tetralogy of Fallot. Human mutation 97 14517948
1999 hFOG-2, a novel zinc finger protein, binds the co-repressor mCtBP2 and modulates GATA-mediated activation. The Journal of biological chemistry 90 10438528
2002 FOG-2 and GATA-4 Are coexpressed in the mouse ovary and can modulate mullerian-inhibiting substance expression. Biology of reproduction 87 12606418
2018 ZFPM2-AS1, a novel lncRNA, attenuates the p53 pathway and promotes gastric carcinogenesis by stabilizing MIF. Oncogene 81 29985481
2008 Ovarian development in mice requires the GATA4-FOG2 transcription complex. Development (Cambridge, England) 81 18927154
2007 Correct dosage of Fog2 and Gata4 transcription factors is critical for fetal testis development in mice. Proceedings of the National Academy of Sciences of the United States of America 78 17848526
2013 FOG2 protein down-regulation by transforming growth factor-β1-induced microRNA-200b/c leads to Akt kinase activation and glomerular mesangial hypertrophy related to diabetic nephropathy. The Journal of biological chemistry 76 23788640
2020 Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinoma. Journal of experimental & clinical cancer research : CR 68 32795316
2002 Developmental expression and spermatogenic stage specificity of transcription factors GATA-1 and GATA-4 and their cofactors FOG-1 and FOG-2 in the mouse testis. European journal of endocrinology 66 12213678
2009 Fog2 is critical for cardiac function and maintenance of coronary vasculature in the adult mouse heart. The Journal of clinical investigation 65 19411759
2010 New mutations in ZFPM2/FOG2 gene in tetralogy of Fallot and double outlet right ventricle. Clinical genetics 62 20807224
2011 Conditional ablation of Gata4 and Fog2 genes in mice reveals their distinct roles in mammalian sexual differentiation. Developmental biology 61 21385577
2014 Mutations in the FOG2/ZFPM2 gene are associated with anomalies of human testis determination. Human molecular genetics 59 24549039
2002 Friend of GATA (FOG)-1 and FOG-2 differentially repress the GATA-dependent activity of multiple gonadal promoters. Endocrinology 58 12239108
2020 LncRNA ZFPM2-AS1 promotes lung adenocarcinoma progression by interacting with UPF1 to destabilize ZFPM2. Molecular oncology 56 31919993
2016 Corticothalamic Projection Neuron Development beyond Subtype Specification: Fog2 and Intersectional Controls Regulate Intraclass Neuronal Diversity. Neuron 55 27321927
2011 Novel ZFPM2/FOG2 variants in patients with double outlet right ventricle. Clinical genetics 52 21919901
2019 lncRNA ZFPM2-AS1 promotes proliferation via miR-18b-5p/VMA21 axis in lung adenocarcinoma. Journal of cellular biochemistry 51 31297866
2007 Candidate genes for congenital diaphragmatic hernia from animal models: sequencing of FOG2 and PDGFRalpha reveals rare variants in diaphragmatic hernia patients. European journal of human genetics : EJHG 48 17568391
2014 Prevalence and penetrance of ZFPM2 mutations and deletions causing congenital diaphragmatic hernia. Clinical genetics 46 24702427
2015 MicroRNA-200c Promotes Suppressive Potential of Myeloid-Derived Suppressor Cells by Modulating PTEN and FOG2 Expression. PloS one 45 26285119
2009 Translational control of FOG-2 expression in cardiomyocytes by microRNA-130a. PloS one 41 19582148
1996 FOG1 and FOG2 genes, required for the transcriptional activation of glucose-repressible genes of Kluyveromyces lactis, are homologous to GAL83 and SNF1 of saccharomyces cerevisiae. Current genetics 41 8598052
2020 YY1-induced lncRNA ZFPM2-AS1 facilitates cell proliferation and invasion in small cell lung cancer via upregulating of TRAF4. Cancer cell international 40 32280300
2002 Retinoid X receptor alpha represses GATA-4-mediated transcription via a retinoid-dependent interaction with the cardiac-enriched repressor FOG-2. The Journal of biological chemistry 37 12480945
2004 FOG-2 competes with GATA-4 for transcriptional coactivator p300 and represses hypertrophic responses in cardiac myocytes. The Journal of biological chemistry 36 15220332
2003 GATA and FOG2 transcription factors differentially regulate the promoter for Kv4.2 K(+) channel gene in cardiac myocytes and PC12 cells. Cardiovascular research 35 14613857
2021 SP1-induced lncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) aggravates glioma progression via the miR-515-5p/Superoxide dismutase 2 (SOD2) axis. Bioengineered 31 34077295
2008 Sex change by gene conversion in a Caenorhabditis elegans fog-2 mutant. Genetics 31 18757925
2016 Hypoxia-Induced MicroRNA-429 Promotes Differentiation of MC3T3-E1 Osteoblastic Cells by Mediating ZFPM2 Expression. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 30 27576955
2014 FOG-2 mediated recruitment of the NuRD complex regulates cardiomyocyte proliferation during heart development. Developmental biology 30 25196150
2001 Conserved cardiogenic functions of the multitype zinc-finger proteins: U-shaped and FOG-2. Trends in cardiovascular medicine 30 11597829
2021 ZFPM2-AS1 transcriptionally mediated by STAT1 regulates thyroid cancer cell growth, migration and invasion via miR-515-5p/TUSC3. Journal of Cancer 29 33976749
2018 MicroRNA-221 promotes cell proliferation, migration, and differentiation by regulation of ZFPM2 in osteoblasts. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 29 30365725
2007 Disruption of friend of GATA 2 gene (FOG-2) by a de novo t(8;10) chromosomal translocation is associated with heart defects and gonadal dysgenesis. Clinical genetics 29 17309641
2005 Expression of Sox8, Sf1, Gata4, Wt1, Dax1, and Fog2 in the mouse ovarian follicle: implications for the regulation of Amh expression. Molecular reproduction and development 29 15625693
2008 Immunomodulation by herpesvirus U51A chemokine receptor via CCL5 and FOG-2 down-regulation plus XCR1 and CCR7 mimicry in human leukocytes. European journal of immunology 28 18286574
2020 LOX family and ZFPM2 as novel diagnostic biomarkers for malignant pleural mesothelioma. Biomarker research 27 31921422
2015 MicroRNA-200 promotes lung cancer cell growth through FOG2-independent AKT activation. IUBMB life 26 26314828
2020 Long Noncoding RNA ZFPM2-AS1 Knockdown Restrains the Development of Retinoblastoma by Modulating the MicroRNA-515/HOXA1/Wnt/β-Catenin Axis. Investigative ophthalmology & visual science 25 32561925
2020 ZFPM2-AS1 facilitates cell growth in esophageal squamous cell carcinoma via up-regulating TRAF4. Bioscience reports 24 32065218
2023 Exosomal ZFPM2-AS1 contributes to tumorigenesis, metastasis, stemness, macrophage polarization, and infiltration in hepatocellular carcinoma through PKM mediated glycolysis. Environmental toxicology 23 36880413
2019 Long noncoding RNA ZFPM2-AS1 is involved in lung adenocarcinoma via miR-511-3p/AFF4 pathway. Journal of cellular biochemistry 23 31692047
2006 FOG-2 attenuates endothelial-to-mesenchymal transformation in the endocardial cushions of the developing heart. Developmental biology 22 17274974
2005 AML1-FOG2 fusion protein in myelodysplasia. Blood 22 15705784
2020 Long noncoding RNA ZFPM2-AS1 regulates ITGB1 by miR-1226-3p to promote cell proliferation and invasion in hepatocellular carcinoma. European review for medical and pharmacological sciences 21 32744687
2017 miR-200c Accelerates Hepatic Stellate Cell-Induced Liver Fibrosis via Targeting the FOG2/PI3K Pathway. BioMed research international 21 28691020
2020 Analysis of variants in GATA4 and FOG2/ZFPM2 demonstrates benign contribution to 46,XY disorders of sex development. Molecular genetics & genomic medicine 19 31962012
2020 Long non‑coding RNA ZFPM2‑AS1 promotes colorectal cancer progression by sponging miR‑137 to regulate TRIM24. Molecular medicine reports 19 33300060
2019 MicroRNA-106b-5p promotes hepatocellular carcinoma development via modulating FOG2. OncoTargets and therapy 18 31406464
2014 Novel missense variants of ZFPM2/FOG2 identified in conotruncal heart defect patients do not impair interaction with GATA4. PloS one 18 25025186
2012 The miR-17-92 cluster regulates FOG-2 expression and inhibits proliferation of mouse embryonic cardiomyocytes. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 18 22267003
2014 Art27 interacts with GATA4, FOG2 and NKX2.5 and is a novel co-repressor of cardiac genes. PloS one 17 24743694
2014 Novel TNS3-MAP3K3 and ZFPM2-ELF5 fusion genes identified by RNA sequencing in multicystic mesothelioma with t(7;17)(p12;q23) and t(8;11)(q23;p13). Cancer letters 17 25484136
2009 Differential developmental expression of transcription factors GATA-4 and GATA-6, their cofactor FOG-2 and downstream target genes in testicular carcinoma in situ and germ cell tumors. European journal of endocrinology 17 19969558
2011 Association of the ZFPM2 gene with antipsychotic-induced parkinsonism in schizophrenia patients. Psychopharmacology 16 21947317
2021 ZFPM2-AS1 facilitates cell proliferation and migration in cutaneous malignant melanoma through modulating miR-650/NOTCH1 signaling. Dermatologic therapy 15 33406278
2010 Gene conversion and DNA sequence polymorphism in the sex-determination gene fog-2 and its paralog ftr-1 in Caenorhabditis elegans. Molecular biology and evolution 15 20133352
2020 Downregulation of lncRNA XIST promotes proliferation and differentiation, limits apoptosis of osteoblasts through regulating miR-203-3p/ZFPM2 axis. Connective tissue research 14 32326773
2020 ZFPM2-AS1 promotes the proliferation, migration, and invasion of human non-small cell lung cancer cells involving the JAK-STAT and AKT pathways. PeerJ 14 33173620
2019 Long noncoding RNA ZFPM2-AS1 promotes the tumorigenesis of renal cell cancer via targeting miR-137. European review for medical and pharmacological sciences 14 31298319
2014 Exome sequencing identifies ZFPM2 as a cause of familial isolated congenital diaphragmatic hernia and possibly cardiovascular malformations. European journal of medical genetics 14 24769157
2021 Long noncoding RNA ZFPM2-AS1 promotes the proliferation, migration, and invasion of hepatocellular carcinoma cells by regulating the miR-576-3p/HIF-1α axis. Anti-cancer drugs 13 34102651
2008 Increased FOG-2 in failing myocardium disrupts thyroid hormone-dependent SERCA2 gene transcription. Circulation research 13 18658259
2020 Bioinformatics analyses and biological function of lncRNA ZFPM2-AS1 and ZFPM2 gene in hepatocellular carcinoma. Oncology letters 12 32382322
2020 Variants of STAR, AMH and ZFPM2/FOG2 May Contribute towards the Broad Phenotype Observed in 46,XY DSD Patients with Heterozygous Variants of NR5A1. International journal of molecular sciences 12 33202802
2016 CpG island shore methylation of ZFPM2 is identified in tetralogy of fallot samples. Pediatric research 12 26959486
2009 Association of HOXA10, ZFPM2, and MMP2 genes with scrotal hernias evaluated via biological candidate gene analyses in pigs. American journal of veterinary research 12 19645582
2024 A Genomic Link From Heart Failure to Atrial Fibrillation Risk: FOG2 Modulates a TBX5/GATA4-Dependent Atrial Gene Regulatory Network. Circulation 11 38189150
2020 LncRNA ZFPM2-AS1 aggravates the malignant development of breast cancer via upregulating JMJD6. European review for medical and pharmacological sciences 11 33215431
2016 A Novel Function of Hepatic FOG2 in Insulin Sensitivity and Lipid Metabolism Through PPARα. Diabetes 11 27207553
2022 lncRNA ZFPM2-AS1 promotes retinoblastoma progression by targeting microRNA miR-511-3p/paired box protein 6 (PAX6) axis. Bioengineered 10 34989314
2014 Identification of novel significant variants of ZFPM2/FOG2 in non-syndromic Tetralogy of Fallot and double outlet right ventricle in a Chinese Han population. Molecular biology reports 10 24469719
2005 ZFPM2/FOG2 and HEY2 genes analysis in nonsyndromic tricuspid atresia. American journal of medical genetics. Part A 10 15643620
2023 ZFPM2-AS1: An Oncogenic Long Non-coding RNA in Multiple Cancer Types. Mini reviews in medicinal chemistry 9 35578882
2012 SUMOylation regulates the transcriptional repression activity of FOG-2 and its association with GATA-4. PloS one 9 23226341
2018 Correction: ZFPM2-AS1, a novel lncRNA, attenuates the p53 pathway and promotes gastric carcinogenesis by stabilizing MIF. Oncogene 8 30108331
2017 Identification of ZFPM2 mutations in sporadic conotruncal heart defect patients. Molecular genetics and genomics : MGG 8 29018978
2012 GATA-4 and FOG-2 expression in pediatric ovarian sex cord-stromal tumors replicates embryonal gonadal phenotype: results from the TREP project. PloS one 8 23029311
2009 Cardiac expression of Tnnt1 requires the GATA4-FOG2 transcription complex. TheScientificWorldJournal 8 19578715
2022 Long Non-coding RNA ZFPM2-AS1: A Novel Biomarker in the Pathogenesis of Human Cancers. Molecular biotechnology 7 35098483
2022 Comprehensive variant calling from whole-genome sequencing identifies a complex inversion that disrupts ZFPM2 in familial congenital diaphragmatic hernia. Molecular genetics & genomic medicine 7 35119225
2022 Genome stability‑related lncRNA ZFPM2‑AS1 promotes tumor progression via miR‑3065‑5p/XRCC4 in hepatocellular carcinoma. International journal of oncology 7 36524359
2020 Long Noncoding RNA ZFPM2-AS1 Enhances the Malignancy of Cervical Cancer by Functioning as a Molecular Sponge of microRNA-511-3p and Consequently Increasing FGFR2 Expression. Cancer management and research 7 32158261
2022 LncRNA ZFPM2-AS1 drives the progression of nasopharyngeal carcinoma via modulating the downstream miR-3612/DTL signaling. Anti-cancer drugs 6 35276693
2015 Glioma Association and Balancing Selection of ZFPM2. PloS one 6 26207917

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