{"gene":"MAFG","run_date":"2026-06-10T02:59:50","timeline":{"discoveries":[{"year":2002,"finding":"NMR solution structure of the MafG DNA-binding domain (residues 1-76) was determined, revealing three alpha-helices and structural similarity to the C. elegans developmental transcription factor Skn-1; the Maf extended homology region (EHR) together with the basic region defines the DNA-binding specificity of Maf family proteins.","method":"NMR spectroscopy","journal":"Nature structural biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — first structure of MafG DNA-binding domain by NMR with functional domain mapping, single study but rigorous structural method","pmids":["11875518"],"is_preprint":false},{"year":1998,"finding":"MafG forms heterodimers with the CNC-bZIP factor TCF11/LCR-F1/Nrf1; the MafG–TCF11 heterodimer binds a 5'-TGCTgaGTCAT-3' sequence (identical to the NF-E2/ARE/heme-responsive element) with higher affinity than TCF11 alone, yet MafG interferes with TCF11 transactivation in a dose-dependent manner, acting as a repressor when co-expressed with TCF11.","method":"Binding-site selection, EMSA, transient transfection reporter assay, in vitro dimerization","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — binding-site selection + EMSA + functional reporter assay, multiple orthogonal methods in one study","pmids":["9421508"],"is_preprint":false},{"year":2000,"finding":"Overexpressed MafG (and MafK) homodimers bind the NQO1 ARE and negatively regulate ARE-mediated NQO1 and GST Ya gene expression and antioxidant induction in HepG2 cells; MafG-Nrf2 heterodimers also repress, whereas Maf-Nrf1 heterodimers fail to bind the NQO1 ARE and show no repressive effect.","method":"Transfection reporter assay, EMSA/band-shift and supershift assays in HepG2 cells","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal EMSA + functional reporter, multiple constructs tested in same study","pmids":["11013233"],"is_preprint":false},{"year":2001,"finding":"MafG (together with Nrf2) forms an EMSA complex (complex X) that binds stress-response elements (StREs) in the heme oxygenase-1 promoter; dominant-negative mutants of both Nrf2 and small Maf (but not other bZIP factors) attenuate cobalt-mediated HO-1 gene activation, placing the Nrf2–MafG heterodimer as the functional unit at the StRE.","method":"EMSA with antibody supershift, dominant-negative transfection, luciferase reporter assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — supershift EMSA + dominant-negative functional test + reporter, multiple orthogonal methods","pmids":["11356853"],"is_preprint":false},{"year":2004,"finding":"Nrf2 transcriptionally activates the mafG gene through a conserved ARE (Ic-ARE) in the mafG proximal promoter; Nrf2/MafG heterodimer binds the Ic-ARE in vivo (ChIP) and in vitro; DEM fails to induce mafG in nrf2-null cells, establishing an autoregulatory feedback loop.","method":"Luciferase reporter assay, ChIP, gel-shift assay, nrf2-null cells","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — ChIP + reporter + null-cell epistasis, multiple orthogonal methods in one study","pmids":["15574414"],"is_preprint":false},{"year":2004,"finding":"MafG binding kinetics to six MARE-related sequences were quantified by surface plasmon resonance (SPR) imaging on a DNA array; kinetic values correlated well with EMSA, validating SPR imaging as a method for comprehensive TF–DNA interaction analysis and confirming sequence-specific binding affinities of MafG.","method":"SPR imaging on double-stranded DNA array, EMSA","journal":"Genes to cells","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro SPR binding assay, single study, primarily methodological but establishes MafG–DNA kinetics","pmids":["15009092"],"is_preprint":false},{"year":2006,"finding":"MafG is conjugated to SUMO-2/3 in vivo; sumoylation-deficient MafG retains normal heterodimer (p45-dependent) activation but loses transcriptional repression activity in vivo; SUMO-dependent repression by MafG is sensitive to histone deacetylase inhibition, indicating MafG homodimer repression requires SUMO-mediated recruitment of an HDAC-containing repressor complex rather than simple competitive DNA binding.","method":"Transgenic mice and cultured cells with wild-type vs. sumoylation-deficient MafG mutant; HDAC inhibitor treatment","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — in vivo transgenic + mutagenesis + pharmacological inhibitor, multiple orthogonal methods","pmids":["16738329"],"is_preprint":false},{"year":2008,"finding":"MafG physically interacts with HIF-1α (identified by yeast two-hybrid, confirmed by SPR and co-localization); MafG knockdown reduces nuclear accumulation of HIF-1α without changing total HIF-1α protein levels, thereby reducing EPO mRNA and HRE-reporter activity, indicating MafG retains HIF-1α in the nucleus to support hypoxic gene activation.","method":"Yeast two-hybrid, SPR, nuclear co-localization (nucleolus with NoLS), siRNA knockdown, luciferase reporter, RT-PCR","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2–3 / Weak — yeast two-hybrid + SPR + KD functional assay, single lab, single study","pmids":["18538669"],"is_preprint":false},{"year":2012,"finding":"Genome-wide ChIP-seq in cells identified co-occupied Nrf2–MafG binding sites enriched for ARE motifs in species-conserved regions; co-occupied sites showed higher enrichment than Nrf2-only sites, and the majority of Nrf2-regulated cytoprotective genes and also glucose metabolism/amino acid transporter genes were located near Nrf2–MafG co-binding sites, demonstrating broad genome-wide cooperative regulation.","method":"ChIP-seq for Nrf2 and MafG","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genome-wide ChIP-seq for both proteins, bioinformatic validation, single study but rigorous","pmids":["22965115"],"is_preprint":false},{"year":2014,"finding":"In BRAF(V600E) CRC cells, MAFG is phosphorylated and elevated via BRAF/MEK/ERK signaling; elevated MAFG binds promoters of MLH1 and other CIMP genes and recruits a corepressor complex containing its heterodimeric partner BACH1, the chromatin remodeling factor CHD8, and DNA methyltransferase DNMT3B, leading to CpG hypermethylation and transcriptional silencing of those genes.","method":"RNAi screen, ChIP-seq, co-immunoprecipitation, pharmacological MEK/ERK inhibition, CRC cell lines and tumor specimens","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — RNAi screen + ChIP + reciprocal Co-IP + cell lines and tumor validation, multiple orthogonal methods replicated in primary tumors","pmids":["25219500"],"is_preprint":false},{"year":2015,"finding":"MAFG is an FXR target gene; hepatic MAFG overexpression represses bile acid synthesis genes (Cyp7a1, Cyp8b1) and alters biliary bile acid composition; MafG(+/-) haploinsufficiency de-represses these same genes with concordant bile acid changes; ChIP-seq identified functional MAFG response elements in bile acid metabolism gene regulatory regions.","method":"Gain-of-function (overexpression), loss-of-function (MafG+/- mice), ChIP-seq, bile acid profiling","journal":"Cell metabolism","confidence":"High","confidence_rationale":"Tier 2 / Strong — complementary gain- and loss-of-function in vivo + ChIP-seq, multiple orthogonal methods","pmids":["25651182"],"is_preprint":false},{"year":2005,"finding":"MafG forms heterodimers with FosB in the nucleus; decreasing extracellular pH from 7.40 to 6.80 enhances MafG–FosB dimerization and augments binding of the heterodimer to AP-1 consensus sequences, leading to increased MMP-1 transcription.","method":"Immunofluorescence co-localization, co-immunoprecipitation/protein binding, EMSA, RT-PCR","journal":"Journal of cellular physiology","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single Co-IP/EMSA with functional reporter, single lab","pmids":["15828020"],"is_preprint":false},{"year":2019,"finding":"A tethered Nrf2–MafG heterodimer (T-N2G), introduced into small Maf triple-knockout fibroblasts, specifically activates Nrf2 target cytoprotective genes (but not Nrf1 targets such as proteasome subunit genes) and preferentially binds CNC-sMaf binding element (CsMBE) motifs genome-wide, providing direct evidence that the Nrf2–MafG heterodimer is sufficient for ARE/CsMBE-dependent transcriptional activation.","method":"Tethered dimer construct in sMaf triple-KO cells, genome-wide ChIP-seq, gene expression analysis","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — unique reconstitution approach in null background + genome-wide binding, rigorous genetic controls","pmids":["31383749"],"is_preprint":false},{"year":2022,"finding":"A tethered Nrf1–MafG heterodimer (T-N1G) specifically activates proteasome subunit genes and genes involved in ER-associated degradation, chaperone, and ubiquitin-mediated degradation pathways through CsMBE binding, demonstrating that Nrf1–MafG heterodimer has a distinct target gene repertoire from Nrf2–MafG; under strong induction, Nrf1 can also activate canonical Nrf2 target genes.","method":"Tethered dimer construct in sMaf triple-KO cells, genome-wide ChIP-seq, gene expression analysis","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — reconstitution in null background + genome-wide binding, same rigorous system as companion Nrf2-MafG study","pmids":["35129372"],"is_preprint":false},{"year":2020,"finding":"In EAE and multiple sclerosis astrocytes, increased MAFG expression cooperates with MAT2α to promote DNA methylation and repress antioxidant/anti-inflammatory transcriptional programs; GM-CSF signaling in astrocytes drives MAFG and MAT2α expression and pro-inflammatory transcriptional modules; in vivo CRISPR-Cas9 perturbation of MAFG modulates CNS pathology in EAE.","method":"Single-cell RNA-seq, Ribotag RNA profiling, ATAC-seq, ChIP-seq, genome-wide DNA methylation analysis, in vivo CRISPR-Cas9 genetic perturbation","journal":"Nature","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal genomic methods + in vivo CRISPR perturbation, replicated across EAE and MS patient samples","pmids":["32051591"],"is_preprint":false},{"year":2020,"finding":"MAFG signaling during diet-induced obesity represses hepatic lncRNA expression; silencing Mafg in mouse hepatocytes and obese mice elicits a fasting-like gene expression profile, improves glucose metabolism, de-represses lncRNAs, and impairs mTOR activation, placing MAFG as a nutrient-sensitive transcriptional repressor in hepatic glucose metabolism.","method":"Gain-of-function (overexpression), RNAi-mediated knockdown in mouse hepatocytes and obese mice, global cistrome analysis, gene expression profiling","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Moderate — complementary gain/loss-of-function in vivo + cistrome analysis, multiple orthogonal methods","pmids":["32005828"],"is_preprint":false},{"year":2018,"finding":"LCA (lithocholic acid) activates MAFG expression through AP-1, NF-κB, and E-box sites in its promoter; MAT2A overexpression increases MAFG promoter activity whereas MAT1A decreases it; MAFG directly interacts with MATα1 and occupies E-box elements to repress transcription; SAMe and UDCA reduce MAFG expression by shared and distinct mechanisms.","method":"Transfection reporter assay, EMSA, ChIP, siRNA knockdown, overexpression, mouse cholestasis models","journal":"Gastroenterology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — EMSA + ChIP + reporter + in vivo models, multiple orthogonal methods in one study","pmids":["29733835"],"is_preprint":false},{"year":2024,"finding":"MafG physically interacts with non-muscle myosin heavy chain IIa (MYH9) to form a transcriptional complex that activates LCN2 expression; site-directed mutation of the MARE motif in the LCN2 promoter blocks MafG binding; MafG knockdown increases hepatic stellate cell ferroptosis and re-expression of LCN2 in MafG-knockdown HSCs restores ferroptosis resistance; HSC-specific AAV6-mediated MafG knockdown promotes ferroptosis and alleviates liver fibrosis in BDL mice.","method":"Co-immunoprecipitation, site-directed mutagenesis of MARE motif, ChIP, siRNA/overexpression, AAV-mediated in vivo knockdown, BDL mouse model","journal":"Cell death and differentiation","confidence":"High","confidence_rationale":"Tier 2 / Moderate — Co-IP + mutagenesis + ChIP + in vivo AAV KD, multiple orthogonal methods","pmids":["38871948"],"is_preprint":false},{"year":1998,"finding":"Germline ablation of mafG in mice results in impaired platelet formation with megakaryocyte proliferation defects and behavioral abnormalities; mafK-null mice are phenotypically normal; compound mafG/mafK knockouts show synthetic lethality and exacerbated erythroid and megakaryocytic deficiencies, demonstrating in vivo functional redundancy between small Maf proteins.","method":"Gene targeting (null alleles replacing coding sequences with lacZ), phenotypic analysis of KO mice","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 2 / Strong — mouse KO with defined megakaryocytic and behavioral phenotype, replicated with compound KO","pmids":["9679061","10716933"],"is_preprint":false},{"year":2023,"finding":"In melanoma, YAP inactivation (triggered by soft matrix/low mechanical force via integrin β8–RhoGDI1–RhoA pathway) relieves YAP-mediated inhibition of MAFG, allowing MAFG to transactivate stemness genes NANOG, SOX2, and NESTIN; MAFG inactivation also restores β8 expression, forming a closed mechanical feedback loop.","method":"Gene silencing, overexpression, mechanotransduction assays (soft vs. stiff matrices), reporter assays","journal":"Research (Washington, D.C.)","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — loss-of-function with defined phenotype and pathway placement, single lab, single study","pmids":["37614365"],"is_preprint":false},{"year":2025,"finding":"MafG forms a functional heterodimer with Bach1 that directly engages the Lcn2 promoter and drives its transcriptional activation; MafG overexpression promotes ferroptosis via iron accumulation and lipid peroxidation in alveolar epithelial cells, and MafG knockdown (via AAV-shMafG) mitigates lung injury and improves survival in sepsis models; the natural compound Anemoside B4 was identified as a MafG inhibitor by SPR.","method":"Co-immunoprecipitation, mass spectrometry, luciferase reporter assay, siRNA/AAV knockdown, in vivo sepsis model (CLP), SPR","journal":"Free radical biology & medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — Co-IP + reporter + in vivo KD, single lab, single study","pmids":["41475687"],"is_preprint":false},{"year":2024,"finding":"MAFG expression is upregulated in spinal cord injury (SCI) astrocytes; MAFG binds the CRYAB promoter and promotes its methylation (involving DNMT3b); MAFG silencing inhibits A1 astrocyte activation and neuroinflammation and improves functional recovery after SCI; 5-Aza (methylation inhibitor) further inhibited A1 activation, while DNMT3b overexpression reversed MAFG-silencing effects.","method":"Rat SCI model, ACM/LPS astrocyte model, siRNA knockdown, RT-PCR, Western blot, immunofluorescence, functional behavior scores","journal":"Immunity, inflammation and disease","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — KD with defined phenotype + pharmacological/genetic epistasis on CRYAB methylation, single lab","pmids":["41555187"],"is_preprint":false},{"year":2021,"finding":"In bladder cancer cells, MAFG transcriptionally activates MAFG-AS1 expression; MAFG-AS1 in turn recruits histone acetyltransferase p300 to promote H3K27ac at the MAFG genomic locus, forming a positive feedback loop.","method":"ChIP, luciferase reporter assay, siRNA/overexpression, co-immunoprecipitation in bladder cancer cells","journal":"Science bulletin","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — ChIP + reporter for MAFG side of feedback, single lab, single study; note this paper primarily concerns lncRNA MAFG-AS1","pmids":["36654385"],"is_preprint":false},{"year":2025,"finding":"MAFG directly activates METTL14 expression in choroidal melanoma; MAFG-METTL14-SCD1 axis promotes lipid remodeling and membrane fluidity driving metastasis; MAFG was shown to transcriptionally activate METTL14 as part of this axis.","method":"Multiplex immunohistochemistry, transcriptomics, lipidomics, METTL14 silencing, mechanistic pathway validation","journal":"Journal of experimental & clinical cancer research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, limited mechanistic detail in abstract regarding MAFG's direct transcriptional activity on METTL14","pmids":["41316357"],"is_preprint":false},{"year":2023,"finding":"MAFG and NFE2L1 (NRF1) bind to a locus (locus 22) in the PD-L1 super-enhancer to drive PD-L1 expression; silencing MAFG reduces BRD4 binding and chromatin loop formation at the PD-L1 locus but has minimal effect on H3K27Ac; MAFG/NFE2L1-silenced cells fail to upregulate PD-L1 in response to LPS and cannot escape T cell-mediated killing.","method":"CRISPR-Cas9 saturated screening, genetic silencing, ChIP for BRD4/H3K27Ac, 3D chromatin conformation (loop formation), T cell killing assay","journal":"Oncogenesis","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — CRISPR screen + ChIP + functional immune assay, single lab, single study","pmids":["37985752"],"is_preprint":false},{"year":2024,"finding":"MAFG directly interacts with MITF in melanoma cells; this MAFG–MITF complex redirects MITF genomic occupancy and modulates MITF-governed transcriptional programs, promoting melanoma dedifferentiation and phenotype switching to a more stem-like state; genetic perturbation in vitro and in vivo shows MAFG is required for the transition from nevi to melanoma.","method":"Co-immunoprecipitation, ChIP/genomic occupancy analysis, overexpression, genetic KO/KD, xenograft models, genetic mouse models of melanoma","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — Co-IP + ChIP occupancy + in vitro and in vivo genetic perturbation in multiple model systems, peer-reviewed replication of preprint findings","pmids":["42168173"],"is_preprint":false},{"year":2021,"finding":"In osteosarcoma cells, MAFG forms a heterodimer with Nrf2 and promotes binding to the ARE to activate Nrf2 target genes; MAFG silencing or knockout inhibits OS cell growth, proliferation, and migration while inducing oxidative injury and apoptosis; miR-4660 directly binds the 3'UTR of MAFG mRNA to suppress MAFG expression and OS progression.","method":"MAFG siRNA/KO, overexpression, 3'UTR luciferase assay, in vivo xenograft (subcutaneous and orthotopic)","journal":"Molecular therapy. Nucleic acids","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — KO + overexpression + in vivo xenograft, single lab; Nrf2 heterodimer claim supported by prior literature","pmids":["33868783"],"is_preprint":false},{"year":2022,"finding":"MAFG interacts with METTL11A protein; METTL11A prevents MAFG degradation through K6 methylation modification; MAFG and NRF2 together bind the promoter region of NPL4 to promote its transcription, forming a METTL11A-MAFG-NPL4 positive feedback loop that promotes bladder cancer cell proliferation.","method":"Co-immunoprecipitation, ChIP, luciferase reporter assay, transcriptome sequencing, in vitro and in vivo proliferation assays","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 2–3 / Weak — Co-IP + ChIP + reporter, single lab, single study","pmids":["40171788"],"is_preprint":false},{"year":2024,"finding":"MAFG binds the HMOX1 (HO-1) promoter and represses its transcription in astrocytes; MAFG knockdown in a mouse CUMS depression model reduces A1 astrocyte-mediated neuroinflammation via restoration of HMOX1 expression; HMOX1 knockdown recapitulates MAFG-driven neuroinflammation.","method":"ChIP (MAFG binding to HMOX1 promoter), siRNA knockdown, CUMS mouse model, RT-PCR, Western blot","journal":"Brain research","confidence":"Medium","confidence_rationale":"Tier 2–3 / Weak — ChIP + KD epistasis in vivo, single lab, single study","pmids":["38977234"],"is_preprint":false}],"current_model":"MAFG is a small bZIP transcription factor that functions exclusively as an obligate dimerization partner: as a homodimer it acts as a transcriptional repressor (requiring SUMO-2/3-mediated recruitment of HDAC-containing complexes for active repression), while as a heterodimer with CNC-family proteins (Nrf2, Nrf1, p45 NF-E2) it activates ARE/CsMBE-dependent cytoprotective, antioxidant, and metabolic genes; with Bach proteins it represses target loci; in cancer contexts, BRAF/MEK/ERK-driven phosphorylation elevates MAFG levels, which then recruits BACH1–CHD8–DNMT3B corepressor complexes to silence tumor suppressor genes via CpG methylation; FXR activation induces MAFG to repress bile acid synthesis genes; in astrocytes, GM-CSF signaling elevates MAFG which cooperates with MAT2α to drive DNA methylation and pro-inflammatory programs; and in melanoma MAFG dimerizes with MITF to redirect its genomic occupancy and promote phenotype switching toward dedifferentiation."},"narrative":{"mechanistic_narrative":"MAFG is a small bZIP transcription factor that functions as an obligate dimerization module, lacking an intrinsic transactivation domain and dictating the DNA-binding specificity and regulatory output of its partners through its basic region and Maf extended homology region [PMID:11875518]. As a homodimer it acts as a transcriptional repressor that depends on SUMO-2/3 conjugation to recruit an HDAC-containing corepressor complex, rather than on simple competitive occupancy of DNA [PMID:16738329]. As a heterodimer with CNC-family factors it confers sequence-specific activation at ARE/CsMBE elements: tethered Nrf2–MafG and Nrf1–MafG dimers reconstituted in small-Maf-null cells are each sufficient to drive distinct cytoprotective programs—antioxidant/metabolic genes for Nrf2–MafG and proteasome/ERAD/degradation genes for Nrf1–MafG—both through CsMBE binding [PMID:31383749, PMID:35129372]. Genome-wide, Nrf2–MafG co-occupancy marks the bulk of Nrf2-regulated cytoprotective and metabolic loci, and MAFG itself is an Nrf2 target gene, establishing an autoregulatory feedback loop [PMID:15574414, PMID:22965115]. MAFG also serves as a tunable transcriptional effector in metabolism and disease: it is an FXR target that represses bile-acid synthesis genes (Cyp7a1, Cyp8b1) [PMID:25651182], a nutrient-responsive repressor of hepatic lncRNAs that restrains glucose metabolism and mTOR activation [PMID:32005828], and in BRAF(V600E) colorectal cancer it is phosphorylated and stabilized by BRAF/MEK/ERK signaling to recruit a BACH1–CHD8–DNMT3B corepressor complex that silences MLH1 and other CIMP genes by CpG hypermethylation [PMID:25219500]. In melanoma, MAFG dimerizes with MITF to redirect MITF genomic occupancy and drive dedifferentiation and phenotype switching, and is required for the nevus-to-melanoma transition [PMID:42168173]. Genetic ablation in mice causes defective platelet/megakaryocyte formation and behavioral abnormalities, with synthetic lethality and erythroid/megakaryocytic deficiency in combination with mafK, demonstrating functional redundancy among small Maf proteins [PMID:9679061, PMID:10716933].","teleology":[{"year":1998,"claim":"Established the foundational principle that MafG is not an autonomous activator but a dimerization partner that modulates a CNC factor, repressing TCF11/Nrf1 transactivation while increasing heterodimer DNA affinity.","evidence":"Binding-site selection, EMSA, and reporter assays with MafG–TCF11 heterodimers","pmids":["9421508"],"confidence":"High","gaps":["Did not resolve whether repression reflects sequestration or active corepressor recruitment","Did not address other CNC partners"]},{"year":1998,"claim":"In vivo gene ablation defined the physiological requirement for MafG in megakaryocyte/platelet biology and revealed redundancy with MafK, distinguishing essential from compensable small-Maf functions.","evidence":"Single and compound mafG/mafK null mice with phenotypic analysis","pmids":["9679061","10716933"],"confidence":"High","gaps":["Did not identify the dimer partners driving each phenotype","Behavioral abnormality mechanism unexplained"]},{"year":2002,"claim":"The NMR structure of the DNA-binding domain explained how the basic region plus Maf extended homology region encode binding specificity, providing the structural basis for partner-dependent site selection.","evidence":"NMR solution structure of MafG residues 1-76","pmids":["11875518"],"confidence":"High","gaps":["No structure of a heterodimer bound to DNA","Did not address how partners reshape specificity"]},{"year":2004,"claim":"Defined MafG as the obligate partner of Nrf2 at the heme oxygenase/StRE and NQO1 ARE and showed MafG is itself an Nrf2 target, revealing an autoregulatory antioxidant feedback circuit; reciprocal EMSA distinguished repressive (homodimer, Nrf2 heterodimer) from inactive (Nrf1) configurations on the NQO1 ARE.","evidence":"Supershift EMSA, dominant-negative tests, ChIP, reporter assays, and nrf2-null cells","pmids":["11013233","11356853","15574414"],"confidence":"High","gaps":["Did not separate cooperative activation from repression mechanistically","In vivo physiological weighting of the feedback loop unaddressed"]},{"year":2006,"claim":"Resolved the mechanism of homodimer repression, showing it requires SUMO-2/3 conjugation to recruit an HDAC-dependent corepressor rather than passive DNA competition, decoupling repression from activation activity.","evidence":"Transgenic mice and cells with wild-type vs sumoylation-deficient MafG plus HDAC inhibition","pmids":["16738329"],"confidence":"High","gaps":["Identity of the recruited HDAC complex not defined","SUMO ligase and deconjugation control unknown"]},{"year":2012,"claim":"Genome-wide mapping demonstrated that Nrf2–MafG co-occupancy, not Nrf2 alone, defines the functional cytoprotective and metabolic cistrome, generalizing the heterodimer principle to the whole genome.","evidence":"ChIP-seq for Nrf2 and MafG with motif analysis","pmids":["22965115"],"confidence":"High","gaps":["Did not test sufficiency of the heterodimer in isolation","Did not distinguish Nrf1 vs Nrf2 contributions at shared sites"]},{"year":2019,"claim":"Tethered-dimer reconstitution in small-Maf-null cells provided direct proof that the Nrf2–MafG heterodimer is sufficient for CsMBE/ARE-dependent activation of cytoprotective genes.","evidence":"Tethered Nrf2–MafG construct in sMaf triple-KO fibroblasts with ChIP-seq","pmids":["31383749"],"confidence":"High","gaps":["Did not address endogenous stoichiometry of free vs tethered dimers","Repression activity not modeled in this system"]},{"year":2022,"claim":"An analogous tethered Nrf1–MafG dimer showed that partner identity assigns MafG to a distinct proteostasis target repertoire, establishing how one small Maf diversifies output across CNC partners.","evidence":"Tethered Nrf1–MafG construct in sMaf triple-KO cells with ChIP-seq and expression profiling","pmids":["35129372"],"confidence":"High","gaps":["Mechanism of target discrimination between Nrf1 and Nrf2 dimers unresolved","Cellular conditions that bias partner choice unknown"]},{"year":2014,"claim":"Linked MafG to oncogenic signaling and epigenetic silencing, showing BRAF/MEK/ERK-driven phosphorylation elevates MAFG to recruit a BACH1–CHD8–DNMT3B complex that hypermethylates and silences CIMP genes including MLH1.","evidence":"RNAi screen, ChIP-seq, reciprocal Co-IP, MEK/ERK inhibition in CRC lines and tumors","pmids":["25219500"],"confidence":"High","gaps":["Phosphorylation sites and how they control stability not fully mapped","Generality beyond BRAF-mutant CRC untested here"]},{"year":2015,"claim":"Defined MafG as an FXR-induced metabolic repressor controlling bile-acid synthesis, extending its repressor role into nuclear-receptor-driven hepatic physiology.","evidence":"Hepatic gain/loss-of-function in mice plus ChIP-seq and bile-acid profiling","pmids":["25651182"],"confidence":"High","gaps":["Dimer partner mediating bile-acid gene repression not identified","Corepressor machinery at these loci undefined"]},{"year":2020,"claim":"Two studies expanded MafG's repressor role into nutrient sensing and DNA-methylation-coupled inflammation: hepatic MafG restrains lncRNAs and mTOR during obesity, and astrocyte MafG cooperates with MAT2α to methylate and repress anti-inflammatory programs in CNS autoimmunity.","evidence":"Cistrome/expression profiling with hepatocyte and obese-mouse perturbation; scRNA-seq, ATAC-seq, ChIP-seq, methylation analysis, and in vivo CRISPR in EAE/MS","pmids":["32005828","32051591"],"confidence":"High","gaps":["Upstream signals coupling MafG to MAT2α/SAM methyl-donor flux only partly defined","Dimer partners at repressed metabolic loci not identified"]},{"year":2024,"claim":"Demonstrated that MafG can rewire a master lineage factor by directly binding MITF, redirecting its occupancy to drive melanoma dedifferentiation and the nevus-to-melanoma transition.","evidence":"Co-IP, ChIP occupancy, and genetic perturbation in melanoma cells, xenografts, and mouse models","pmids":["42168173"],"confidence":"High","gaps":["Structural basis of the MAFG–MITF interaction unknown","How MAFG levels are set in melanoma not fully resolved"]},{"year":null,"claim":"It remains unresolved how MafG's choice among many partners (CNC factors, Bach1, MITF, FosB, MYH9) is governed in a given cell, and how its dual activator/repressor outputs and post-translational control are coordinated across tissues.","evidence":"No single study in the corpus integrates partner selection, modification state, and output across contexts","pmids":[],"confidence":"Low","gaps":["No mechanism assigning partner choice to cell state","No unified model of phosphorylation/SUMO/methylation control over MafG abundance and activity","Most non-CNC partner interactions rest on single Co-IP studies"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1,2,8,12,13,10,9]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[0,1,5,8]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,2,12,13,25]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[6,7,11]}],"pathway":[{"term_id":"R-HSA-8953897","term_label":"Cellular responses to stimuli","supporting_discovery_ids":[2,3,4,8,12]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[1,8,12,13]},{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[10,15]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[9,14,25]}],"complexes":[],"partners":["NFE2L2","NFE2L1","BACH1","CHD8","DNMT3B","MITF","MAT2A","HIF1A"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O15525","full_name":"Transcription factor MafG","aliases":["V-maf musculoaponeurotic fibrosarcoma oncogene homolog G","hMAF"],"length_aa":162,"mass_kda":17.9,"function":"Since they lack a putative transactivation domain, the small Mafs behave as transcriptional repressors when they dimerize among themselves (PubMed:11154691). However, they seem to serve as transcriptional activators by dimerizing with other (usually larger) basic-zipper proteins, such as NFE2, NFE2L1 and NFE2L2, and recruiting them to specific DNA-binding sites (PubMed:11154691, PubMed:8932385, PubMed:9421508). Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NFE2L2 transcription factor (PubMed:11154691). Transcription factor, component of erythroid-specific transcription factor NFE2L2 (PubMed:11154691). Activates globin gene expression when associated with NFE2L2 (PubMed:11154691). May be involved in signal transduction of extracellular H(+) (By similarity)","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/O15525/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MAFG","classification":"Not Classified","n_dependent_lines":50,"n_total_lines":1208,"dependency_fraction":0.041390728476821195},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/MAFG","total_profiled":1310},"omim":[{"mim_id":"616770","title":"MICRO RNA 218-1; MIR218-1","url":"https://www.omim.org/entry/616770"},{"mim_id":"604877","title":"MAF bZIP TRANSCRIPTION FACTOR F; MAFF","url":"https://www.omim.org/entry/604877"},{"mim_id":"602020","title":"MAF bZIP TRANSCRIPTION FACTOR G; MAFG","url":"https://www.omim.org/entry/602020"},{"mim_id":"601637","title":"CYTOCHROME P450, FAMILY 51, SUBFAMILY A, POLYPEPTIDE 1; CYP51A1","url":"https://www.omim.org/entry/601637"},{"mim_id":"601490","title":"NUCLEAR FACTOR ERYTHROID 2, p45 SUBUNIT; NFE2","url":"https://www.omim.org/entry/601490"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MAFG"},"hgnc":{"alias_symbol":["MGC13090","MGC20149"],"prev_symbol":[]},"alphafold":{"accession":"O15525","domains":[{"cath_id":"1.20.5.170","chopping":"25-122","consensus_level":"medium","plddt":97.2086,"start":25,"end":122}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O15525","model_url":"https://alphafold.ebi.ac.uk/files/AF-O15525-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O15525-F1-predicted_aligned_error_v6.png","plddt_mean":79.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MAFG","jax_strain_url":"https://www.jax.org/strain/search?query=MAFG"},"sequence":{"accession":"O15525","fasta_url":"https://rest.uniprot.org/uniprotkb/O15525.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O15525/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O15525"}},"corpus_meta":[{"pmid":"32051591","id":"PMC_32051591","title":"MAFG-driven astrocytes promote CNS inflammation.","date":"2020","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/32051591","citation_count":382,"is_preprint":false},{"pmid":"22965115","id":"PMC_22965115","title":"Nrf2-MafG heterodimers contribute globally to antioxidant and metabolic networks.","date":"2012","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/22965115","citation_count":361,"is_preprint":false},{"pmid":"27058431","id":"PMC_27058431","title":"Small Maf proteins (MafF, MafG, MafK): History, structure and function.","date":"2016","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/27058431","citation_count":199,"is_preprint":false},{"pmid":"25219500","id":"PMC_25219500","title":"The BRAF oncoprotein functions through the transcriptional repressor MAFG to mediate the CpG Island Methylator phenotype.","date":"2014","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/25219500","citation_count":184,"is_preprint":false},{"pmid":"11013233","id":"PMC_11013233","title":"Small maf (MafG and MafK) proteins negatively regulate antioxidant response element-mediated expression and antioxidant induction of the NAD(P)H:Quinone oxidoreductase1 gene.","date":"2000","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11013233","citation_count":183,"is_preprint":false},{"pmid":"11356853","id":"PMC_11356853","title":"Cobalt induces heme oxygenase-1 expression by a hypoxia-inducible factor-independent mechanism in Chinese hamster ovary cells: regulation by Nrf2 and MafG transcription factors.","date":"2001","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11356853","citation_count":132,"is_preprint":false},{"pmid":"22721719","id":"PMC_22721719","title":"The small MAF transcription factors MAFF, MAFG and MAFK: current knowledge and perspectives.","date":"2012","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/22721719","citation_count":127,"is_preprint":false},{"pmid":"15574414","id":"PMC_15574414","title":"Nrf2 transcriptionally activates the mafG gene through an antioxidant response element.","date":"2004","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15574414","citation_count":105,"is_preprint":false},{"pmid":"9421508","id":"PMC_9421508","title":"Interaction of the CNC-bZIP factor TCF11/LCR-F1/Nrf1 with MafG: binding-site selection and regulation of transcription.","date":"1998","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/9421508","citation_count":105,"is_preprint":false},{"pmid":"9679061","id":"PMC_9679061","title":"Impaired megakaryopoiesis and behavioral defects in mafG-null mutant mice.","date":"1998","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/9679061","citation_count":95,"is_preprint":false},{"pmid":"25651182","id":"PMC_25651182","title":"MAFG is a transcriptional repressor of bile acid synthesis and metabolism.","date":"2015","source":"Cell metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/25651182","citation_count":81,"is_preprint":false},{"pmid":"10716933","id":"PMC_10716933","title":"Perinatal synthetic lethality and hematopoietic defects in compound mafG::mafK mutant mice.","date":"2000","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/10716933","citation_count":78,"is_preprint":false},{"pmid":"29733835","id":"PMC_29733835","title":"Mechanisms of MAFG Dysregulation in Cholestatic Liver Injury and Development of Liver Cancer.","date":"2018","source":"Gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/29733835","citation_count":77,"is_preprint":false},{"pmid":"30348529","id":"PMC_30348529","title":"LncRNA MAFG-AS1 promotes the progression of colorectal cancer by sponging miR-147b and activation of NDUFA4.","date":"2018","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/30348529","citation_count":77,"is_preprint":false},{"pmid":"15009092","id":"PMC_15009092","title":"Evaluation of MafG interaction with Maf recognition element arrays by surface plasmon resonance imaging technique.","date":"2004","source":"Genes to cells : devoted to molecular & cellular mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/15009092","citation_count":58,"is_preprint":false},{"pmid":"30599080","id":"PMC_30599080","title":"LncRNA MAFG-AS1 facilitates the migration and invasion of NSCLC cell via sponging miR-339-5p from MMP15.","date":"2019","source":"Cell biology international","url":"https://pubmed.ncbi.nlm.nih.gov/30599080","citation_count":55,"is_preprint":false},{"pmid":"31211984","id":"PMC_31211984","title":"LncRNA MAFG-AS1 boosts the proliferation of lung adenocarcinoma cells via regulating miR-744-5p/MAFG axis.","date":"2019","source":"European journal of pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/31211984","citation_count":54,"is_preprint":false},{"pmid":"8886803","id":"PMC_8886803","title":"Oxidative stress induces the levels of a MafG homolog in hamster HA-1 cells.","date":"1996","source":"Free radical biology & medicine","url":"https://pubmed.ncbi.nlm.nih.gov/8886803","citation_count":53,"is_preprint":false},{"pmid":"29158814","id":"PMC_29158814","title":"DNA Methylation of miR-7 is a Mechanism Involved in Platinum Response through MAFG Overexpression in Cancer Cells.","date":"2017","source":"Theranostics","url":"https://pubmed.ncbi.nlm.nih.gov/29158814","citation_count":52,"is_preprint":false},{"pmid":"16738329","id":"PMC_16738329","title":"MafG sumoylation is required for active transcriptional repression.","date":"2006","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/16738329","citation_count":47,"is_preprint":false},{"pmid":"25896808","id":"PMC_25896808","title":"Compound mouse mutants of bZIP transcription factors Mafg and Mafk reveal a regulatory network of non-crystallin genes associated with cataract.","date":"2015","source":"Human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/25896808","citation_count":46,"is_preprint":false},{"pmid":"36654385","id":"PMC_36654385","title":"MAFG-AS1/MAFG positive feedback loop contributes to cisplatin resistance in bladder urothelial carcinoma through antagonistic ferroptosis.","date":"2021","source":"Science bulletin","url":"https://pubmed.ncbi.nlm.nih.gov/36654385","citation_count":43,"is_preprint":false},{"pmid":"11875518","id":"PMC_11875518","title":"Solution structure of the DNA-binding domain of MafG.","date":"2002","source":"Nature structural biology","url":"https://pubmed.ncbi.nlm.nih.gov/11875518","citation_count":42,"is_preprint":false},{"pmid":"32005828","id":"PMC_32005828","title":"A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism.","date":"2020","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/32005828","citation_count":41,"is_preprint":false},{"pmid":"33098638","id":"PMC_33098638","title":"Cross-talk between the ER pathway and the lncRNA MAFG-AS1/miR-339-5p/ CDK2 axis promotes progression of ER+ breast cancer and confers tamoxifen resistance.","date":"2020","source":"Aging","url":"https://pubmed.ncbi.nlm.nih.gov/33098638","citation_count":41,"is_preprint":false},{"pmid":"33377647","id":"PMC_33377647","title":"MAFG-AS1 promotes tumor progression via regulation of the HuR/PTBP1 axis in bladder urothelial carcinoma.","date":"2020","source":"Clinical and translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/33377647","citation_count":40,"is_preprint":false},{"pmid":"38871948","id":"PMC_38871948","title":"MafG/MYH9-LCN2 axis promotes liver fibrosis through inhibiting ferroptosis of hepatic stellate cells.","date":"2024","source":"Cell death and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/38871948","citation_count":38,"is_preprint":false},{"pmid":"31002134","id":"PMC_31002134","title":"LncRNA MAFG-AS1 promotes the aggressiveness of breast carcinoma through regulating miR-339-5p/MMP15.","date":"2019","source":"European review for medical and pharmacological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/31002134","citation_count":38,"is_preprint":false},{"pmid":"32371093","id":"PMC_32371093","title":"Opposite effects of the FXR agonist obeticholic acid on Mafg and Nrf2 mediate the development of acute liver injury in rodent models of cholestasis.","date":"2020","source":"Biochimica et biophysica acta. Molecular and cell biology of lipids","url":"https://pubmed.ncbi.nlm.nih.gov/32371093","citation_count":38,"is_preprint":false},{"pmid":"29138682","id":"PMC_29138682","title":"miR-128 Is Implicated in Stress Responses by Targeting MAFG in Skeletal Muscle Cells.","date":"2017","source":"Oxidative medicine and cellular longevity","url":"https://pubmed.ncbi.nlm.nih.gov/29138682","citation_count":36,"is_preprint":false},{"pmid":"11772409","id":"PMC_11772409","title":"Differential induction of mafF, mafG and mafK expression by electrophile-response-element activators.","date":"2002","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/11772409","citation_count":33,"is_preprint":false},{"pmid":"33868783","id":"PMC_33868783","title":"MAFG-driven osteosarcoma cell progression is inhibited by a novel miRNA miR-4660.","date":"2021","source":"Molecular therapy. Nucleic acids","url":"https://pubmed.ncbi.nlm.nih.gov/33868783","citation_count":32,"is_preprint":false},{"pmid":"33808771","id":"PMC_33808771","title":"A MAPK/miR-29 Axis Suppresses Melanoma by Targeting MAFG and MYBL2.","date":"2021","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/33808771","citation_count":31,"is_preprint":false},{"pmid":"33367930","id":"PMC_33367930","title":"Regulatory effect of the MAFG‑AS1/miR‑150‑5p/MYB axis on the proliferation and migration of breast cancer cells.","date":"2020","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/33367930","citation_count":31,"is_preprint":false},{"pmid":"33400245","id":"PMC_33400245","title":"LncRNA MAFG-AS1 regulates miR-125b-5p/SphK1 axis to promote the proliferation, migration, and invasion of bladder cancer cells.","date":"2021","source":"Human cell","url":"https://pubmed.ncbi.nlm.nih.gov/33400245","citation_count":31,"is_preprint":false},{"pmid":"30053382","id":"PMC_30053382","title":"MAFG is a potential therapeutic target to restore chemosensitivity in cisplatin-resistant cancer cells by increasing reactive oxygen species.","date":"2018","source":"Translational research : the journal of laboratory and clinical medicine","url":"https://pubmed.ncbi.nlm.nih.gov/30053382","citation_count":31,"is_preprint":false},{"pmid":"35773412","id":"PMC_35773412","title":"AKR1C3 regulated by NRF2/MAFG complex promotes proliferation via stabilizing PARP1 in hepatocellular carcinoma.","date":"2022","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/35773412","citation_count":30,"is_preprint":false},{"pmid":"31383749","id":"PMC_31383749","title":"Direct and Specific Functional Evaluation of the Nrf2 and MafG Heterodimer by Introducing a Tethered Dimer into Small Maf-Deficient Cells.","date":"2019","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/31383749","citation_count":30,"is_preprint":false},{"pmid":"31572506","id":"PMC_31572506","title":"Long noncoding RNA MAFG-AS1 promotes proliferation, migration and invasion of hepatocellular carcinoma cells through downregulation of miR-6852.","date":"2019","source":"Experimental and therapeutic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/31572506","citation_count":28,"is_preprint":false},{"pmid":"33813778","id":"PMC_33813778","title":"HBx-upregulated MAFG-AS1 promotes cell proliferation and migration of hepatoma cells by enhancing MAFG expression and stabilizing nonmuscle myosin IIA.","date":"2021","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/33813778","citation_count":25,"is_preprint":false},{"pmid":"34386494","id":"PMC_34386494","title":"Long Non-coding RNA MAFG-AS1 Promotes Cell Proliferation, Migration, and EMT by miR-3196/STRN4 in Drug-Resistant Cells of Liver Cancer.","date":"2021","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/34386494","citation_count":24,"is_preprint":false},{"pmid":"32801913","id":"PMC_32801913","title":"LncRNA MAFG-AS1 Accelerates Cell Migration, Invasion and Aerobic Glycolysis of Esophageal Squamous Cell Carcinoma Cells via miR-765/PDX1 Axis.","date":"2020","source":"Cancer management and research","url":"https://pubmed.ncbi.nlm.nih.gov/32801913","citation_count":23,"is_preprint":false},{"pmid":"34035482","id":"PMC_34035482","title":"LncRNA MAFG-AS1 promotes the malignant phenotype of ovarian cancer by upregulating NFKB1-dependent IGF1.","date":"2021","source":"Cancer gene therapy","url":"https://pubmed.ncbi.nlm.nih.gov/34035482","citation_count":22,"is_preprint":false},{"pmid":"33165437","id":"PMC_33165437","title":"Long non-coding RNA MAFG-AS1 knockdown blocks malignant progression in breast cancer cells by inactivating JAK2/STAT3 signaling pathway via MAFG-AS1/miR-3196/TFAP2A axis.","date":"2020","source":"International journal of clinical and experimental pathology","url":"https://pubmed.ncbi.nlm.nih.gov/33165437","citation_count":21,"is_preprint":false},{"pmid":"35513366","id":"PMC_35513366","title":"Long non-coding RNA MAFG-AS1 promotes proliferation and metastasis of breast cancer by modulating STC2 pathway.","date":"2022","source":"Cell death discovery","url":"https://pubmed.ncbi.nlm.nih.gov/35513366","citation_count":20,"is_preprint":false},{"pmid":"33238264","id":"PMC_33238264","title":"LncRNA MAFG-AS1 Promotes the Progression of Bladder Cancer by Targeting the miR-143-3p/COX-2 Axis.","date":"2020","source":"Pathobiology : journal of immunopathology, molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/33238264","citation_count":19,"is_preprint":false},{"pmid":"32176822","id":"PMC_32176822","title":"LncRNA MAFG-AS1 regulates human periodontal ligament stem cell proliferation and Toll-like receptor 4 expression.","date":"2020","source":"Oral diseases","url":"https://pubmed.ncbi.nlm.nih.gov/32176822","citation_count":19,"is_preprint":false},{"pmid":"33298078","id":"PMC_33298078","title":"MAFG-AS1 aggravates the progression of pancreatic cancer by sponging miR-3196 to boost NFIX.","date":"2020","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/33298078","citation_count":19,"is_preprint":false},{"pmid":"33093810","id":"PMC_33093810","title":"Downregulation of long non-coding RNA MAFG-AS1 represses tumorigenesis of colorectal cancer cells through the microRNA-149-3p-dependent inhibition of HOXB8.","date":"2020","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/33093810","citation_count":18,"is_preprint":false},{"pmid":"18538669","id":"PMC_18538669","title":"MafG controls the hypoxic response of cells by accumulating HIF-1alpha in the nuclei.","date":"2008","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/18538669","citation_count":17,"is_preprint":false},{"pmid":"37614365","id":"PMC_37614365","title":"YAP Inactivation by Soft Mechanotransduction Relieves MAFG for Tumor Cell Dedifferentiation.","date":"2023","source":"Research (Washington, D.C.)","url":"https://pubmed.ncbi.nlm.nih.gov/37614365","citation_count":16,"is_preprint":false},{"pmid":"35129372","id":"PMC_35129372","title":"Target Gene Diversity of the Nrf1-MafG Transcription Factor Revealed by a Tethered Heterodimer.","date":"2022","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/35129372","citation_count":15,"is_preprint":false},{"pmid":"35653827","id":"PMC_35653827","title":"LncRNA MAFG-AS1 deregulated in breast cancer affects autophagy and progression of breast cancer by interacting with miR-3612 and FKBP4 invitro.","date":"2022","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/35653827","citation_count":15,"is_preprint":false},{"pmid":"34535081","id":"PMC_34535081","title":"Proteome-scale profiling reveals MAFF and MAFG as two novel key transcription factors involved in palmitic acid-induced umbilical vein endothelial cell apoptosis.","date":"2021","source":"BMC cardiovascular disorders","url":"https://pubmed.ncbi.nlm.nih.gov/34535081","citation_count":15,"is_preprint":false},{"pmid":"33336731","id":"PMC_33336731","title":"Long noncoding RNA MAFG-AS1 facilitates the progression of hepatocellular carcinoma via targeting miR-3196/OTX1 axis.","date":"2020","source":"European review for medical and pharmacological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/33336731","citation_count":14,"is_preprint":false},{"pmid":"35275356","id":"PMC_35275356","title":"LncRNA MAFG-AS1 Promotes Lung Adenocarcinoma Cell Migration and Invasion by Targeting miR-3196 and Regulating SOX12 Expression.","date":"2022","source":"Molecular biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/35275356","citation_count":14,"is_preprint":false},{"pmid":"36092713","id":"PMC_36092713","title":"Deficiency of the bZIP transcription factors Mafg and Mafk causes misexpression of genes in distinct pathways and results in lens embryonic developmental defects.","date":"2022","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/36092713","citation_count":14,"is_preprint":false},{"pmid":"15828020","id":"PMC_15828020","title":"Extracellular acidification enhances DNA binding activity of MafG-FosB heterodimer.","date":"2005","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/15828020","citation_count":14,"is_preprint":false},{"pmid":"33618612","id":"PMC_33618612","title":"Silencing of LINC00284 inhibits cell proliferation and migration in oral squamous cell carcinoma by the miR-211-3p/MAFG axis and FUS/KAZN axis.","date":"2021","source":"Cancer biology & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/33618612","citation_count":14,"is_preprint":false},{"pmid":"9286713","id":"PMC_9286713","title":"Molecular characterization and localization of the human MAFG gene.","date":"1997","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/9286713","citation_count":13,"is_preprint":false},{"pmid":"10724342","id":"PMC_10724342","title":"Cloning of MafG homologue from the rat brain by differential display and its expression after hypercapnic stimulation.","date":"2000","source":"Molecular and cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10724342","citation_count":13,"is_preprint":false},{"pmid":"33911899","id":"PMC_33911899","title":"LncRNA MAFG-AS1 Suppresses the Maturation of miR-34a to Promote Glioblastoma Cell Proliferation.","date":"2021","source":"Cancer management and research","url":"https://pubmed.ncbi.nlm.nih.gov/33911899","citation_count":12,"is_preprint":false},{"pmid":"35117325","id":"PMC_35117325","title":"Long noncoding RNA MAFG-AS1 facilitates bladder cancer tumorigenesis via regulation of miR-143-3p/SERPINE1 axis.","date":"2020","source":"Translational cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/35117325","citation_count":12,"is_preprint":false},{"pmid":"37105079","id":"PMC_37105079","title":"Long non-coding RNA MAFG-AS1: A promising therapeutic target for human cancers.","date":"2023","source":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","url":"https://pubmed.ncbi.nlm.nih.gov/37105079","citation_count":11,"is_preprint":false},{"pmid":"11583919","id":"PMC_11583919","title":"MafG-2 is a novel Maf protein that is expressed by stimulation of extracellular H(+).","date":"2001","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/11583919","citation_count":11,"is_preprint":false},{"pmid":"34303079","id":"PMC_34303079","title":"Discovery and characterization of novel peptide inhibitors of the NRF2/MAFG/DNA ternary complex for the treatment of cancer.","date":"2021","source":"European journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/34303079","citation_count":11,"is_preprint":false},{"pmid":"33989902","id":"PMC_33989902","title":"LncRNA MAFG-AS1 affects the tumorigenesis of breast cancer cells via the miR-574-5p/SOD2 axis.","date":"2021","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/33989902","citation_count":11,"is_preprint":false},{"pmid":"37941063","id":"PMC_37941063","title":"LncRNA MAFG-AS1 is involved in human cancer progression.","date":"2023","source":"European journal of medical research","url":"https://pubmed.ncbi.nlm.nih.gov/37941063","citation_count":9,"is_preprint":false},{"pmid":"37985752","id":"PMC_37985752","title":"Identifying a locus in super-enhancer and its resident NFE2L1/MAFG as transcriptional factors that drive PD-L1 expression and immune evasion.","date":"2023","source":"Oncogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/37985752","citation_count":9,"is_preprint":false},{"pmid":"37428861","id":"PMC_37428861","title":"Transcription factor ETV1-induced lncRNA MAFG-AS1 promotes migration, invasion, and epithelial-mesenchymal transition of pancreatic cancer cells by recruiting IGF2BP2 to stabilize ETV1 expression.","date":"2023","source":"Growth factors (Chur, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/37428861","citation_count":8,"is_preprint":false},{"pmid":"36034393","id":"PMC_36034393","title":"Long Non-Coding RNA MAFG-AS1 as a Potential Biomarker for Hepatocellular Carcinoma: Linkage with Tumor Features, Markers, Liver Functions, and Survival Profile.","date":"2022","source":"Frontiers in surgery","url":"https://pubmed.ncbi.nlm.nih.gov/36034393","citation_count":8,"is_preprint":false},{"pmid":"38474419","id":"PMC_38474419","title":"LncRNA NEAT1/miR-146a-5p Axis Restores Normal Angiogenesis in Diabetic Foot Ulcers by Targeting mafG.","date":"2024","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/38474419","citation_count":8,"is_preprint":false},{"pmid":"36229729","id":"PMC_36229729","title":"LncRNA MAFG-AS1-induced acute myeloid leukemia development via modulating miR-147b/HOXA9.","date":"2022","source":"Environmental science and pollution research international","url":"https://pubmed.ncbi.nlm.nih.gov/36229729","citation_count":7,"is_preprint":false},{"pmid":"36214714","id":"PMC_36214714","title":"lncRNA MAFG‑AS1 enhances radioresistance of glioblastoma cells via miR‑642a‑5p/Notch1 axis.","date":"2022","source":"Acta neurobiologiae experimentalis","url":"https://pubmed.ncbi.nlm.nih.gov/36214714","citation_count":7,"is_preprint":false},{"pmid":"32903907","id":"PMC_32903907","title":"lncRNA MAFG-AS1 Contributes to Esophageal Squamous-Cell Carcinoma Progression via Regulating miR143/LASP1.","date":"2020","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/32903907","citation_count":7,"is_preprint":false},{"pmid":"34591387","id":"PMC_34591387","title":"LncRNA MAFG-AS1 Upregulates Polo-Like Kinase-1 by Sponging miR-505 to Promote Gastric Adenocarcinoma Cell Proliferation.","date":"2021","source":"Critical reviews in eukaryotic gene expression","url":"https://pubmed.ncbi.nlm.nih.gov/34591387","citation_count":7,"is_preprint":false},{"pmid":"36736142","id":"PMC_36736142","title":"A review on the roles and molecular mechanisms of MAFG-AS1 in oncogenesis.","date":"2023","source":"Pathology, research and practice","url":"https://pubmed.ncbi.nlm.nih.gov/36736142","citation_count":6,"is_preprint":false},{"pmid":"33819748","id":"PMC_33819748","title":"The small protein MafG plays a critical role in MC3T3-E1 cell apoptosis induced by simulated microgravity and radiation.","date":"2021","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/33819748","citation_count":6,"is_preprint":false},{"pmid":"36096331","id":"PMC_36096331","title":"MafG-like contribute to copper and cadmium induced antioxidant response by regulating antioxidant enzyme in Procambarus clarkii.","date":"2022","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/36096331","citation_count":5,"is_preprint":false},{"pmid":"20813153","id":"PMC_20813153","title":"Intrinsic and extrinsic effects of mafG deficiency on hematopoietic recovery following bone marrow transplant.","date":"2010","source":"Experimental hematology","url":"https://pubmed.ncbi.nlm.nih.gov/20813153","citation_count":5,"is_preprint":false},{"pmid":"37351806","id":"PMC_37351806","title":"Carcinogenic roles of MAFG-AS1 in human cancers.","date":"2023","source":"Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico","url":"https://pubmed.ncbi.nlm.nih.gov/37351806","citation_count":4,"is_preprint":false},{"pmid":"9763667","id":"PMC_9763667","title":"Structure and chromosome mapping of the human small maf-genes MAFG and MAFK.","date":"1998","source":"Cytogenetics and cell genetics","url":"https://pubmed.ncbi.nlm.nih.gov/9763667","citation_count":4,"is_preprint":false},{"pmid":"39735608","id":"PMC_39735608","title":"MAFG-DT promotes prostate cancer bone metastasis through activation of the Wnt/β-catenin pathway.","date":"2024","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/39735608","citation_count":3,"is_preprint":false},{"pmid":"38985298","id":"PMC_38985298","title":"A possible role of lncRNA MEG3 and lncRNA MAFG-AS1 on miRNA 147-b in the pathogenesis of Behcet's disease.","date":"2024","source":"Immunogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/38985298","citation_count":3,"is_preprint":false},{"pmid":"34976178","id":"PMC_34976178","title":"LncRNA EIF3J-AS1 functions as an oncogene by regulating MAFG to promote prostate cancer progression.","date":"2022","source":"Journal of Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/34976178","citation_count":3,"is_preprint":false},{"pmid":"16263136","id":"PMC_16263136","title":"Neuronal expression of nuclear transcription factor MafG in the rat medulla oblongata after baroreceptor stimulation.","date":"2005","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/16263136","citation_count":3,"is_preprint":false},{"pmid":"39282450","id":"PMC_39282450","title":"The small MAF transcription factor MAFG co-opts MITF to promote melanoma progression.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/39282450","citation_count":2,"is_preprint":false},{"pmid":"40585189","id":"PMC_40585189","title":"Curcumol targets the FTO/MAFG-AS1 axis to alleviate diabetic retinopathy via epigenetic remodeling and nanodelivery-based microenvironment modulation.","date":"2025","source":"World journal of diabetes","url":"https://pubmed.ncbi.nlm.nih.gov/40585189","citation_count":2,"is_preprint":false},{"pmid":"41316357","id":"PMC_41316357","title":"Novel MAFG-METTL14-SCD1 axis regulates lipid metabolism mediating choroidal melanoma distant metastasis.","date":"2025","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/41316357","citation_count":1,"is_preprint":false},{"pmid":"41475687","id":"PMC_41475687","title":"The MafG/Bach1-Lcn2 transcriptional axis drives ferroptosis in sepsis-induced acute lung injury via disrupting redox homeostasis.","date":"2025","source":"Free radical biology & medicine","url":"https://pubmed.ncbi.nlm.nih.gov/41475687","citation_count":1,"is_preprint":false},{"pmid":"38977234","id":"PMC_38977234","title":"Inhibition of HMOX1 by MAFG potentiates the development of depression‑like behavior in mice associated with astrocyte-mediated neuroinflammation.","date":"2024","source":"Brain research","url":"https://pubmed.ncbi.nlm.nih.gov/38977234","citation_count":1,"is_preprint":false},{"pmid":"40171788","id":"PMC_40171788","title":"A novel feedback regulation loop of METTL11A-MAFG-NPL4 promotes bladder cancer cell proliferation and tumor progression.","date":"2025","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/40171788","citation_count":1,"is_preprint":false},{"pmid":"40372661","id":"PMC_40372661","title":"Overexpression of MAFG-AS1 in ovarian cancer promotes glucose metabolism reprogramming and malignant biological behavior of ovarian cancer cells by regulating HIF-1α.","date":"2025","source":"Discover oncology","url":"https://pubmed.ncbi.nlm.nih.gov/40372661","citation_count":1,"is_preprint":false},{"pmid":"41555187","id":"PMC_41555187","title":"MAFG Induces the Methylation of CRYAB to Promote the Activation of A1 Astrocyte After Spinal Cord Injury.","date":"2026","source":"Immunity, inflammation and disease","url":"https://pubmed.ncbi.nlm.nih.gov/41555187","citation_count":1,"is_preprint":false},{"pmid":"2509820","id":"PMC_2509820","title":"Partial purification of a macrophage-activating factor for glucose consumption (MAF-G) produced by a human T-cell hybridoma and its relation to a growth-promoting factor.","date":"1989","source":"Lymphokine research","url":"https://pubmed.ncbi.nlm.nih.gov/2509820","citation_count":1,"is_preprint":false},{"pmid":"41160238","id":"PMC_41160238","title":"Extracellular vesicles-derived LncRNA MAFG-AS1 predicts clinical response to pembrolizumab in patients with advanced urothelial carcinoma.","date":"2025","source":"Molecular biology reports","url":"https://pubmed.ncbi.nlm.nih.gov/41160238","citation_count":0,"is_preprint":false},{"pmid":"42168173","id":"PMC_42168173","title":"A MAFG~MITF complex drives melanoma phenotype switching and progression.","date":"2026","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/42168173","citation_count":0,"is_preprint":false},{"pmid":"41923123","id":"PMC_41923123","title":"The MAFG-AS1/G6PD axis reduces platinum sensitivity in colorectal cancer through pentose phosphate pathway activation.","date":"2026","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/41923123","citation_count":0,"is_preprint":false},{"pmid":"33335407","id":"PMC_33335407","title":"lncRNA MAFG-AS1 Contributes to Esophageal Squamous-Cell Carcinoma Progression via Regulating miR143/LASP1 [Retraction].","date":"2020","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/33335407","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.12.31.630767","title":"Persistent DNA methylation and downregulation of homeostatic genes in astrocytes after pilocarpine-induced status epilepticus: Implications for epileptogenesis","date":"2025-01-01","source":"bioRxiv","url":"https://doi.org/10.1101/2024.12.31.630767","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":51617,"output_tokens":7365,"usd":0.132663,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":16581,"output_tokens":4399,"usd":0.09644,"stage2_stop_reason":"end_turn"},"total_usd":0.229103,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2002,\n      \"finding\": \"NMR solution structure of the MafG DNA-binding domain (residues 1-76) was determined, revealing three alpha-helices and structural similarity to the C. elegans developmental transcription factor Skn-1; the Maf extended homology region (EHR) together with the basic region defines the DNA-binding specificity of Maf family proteins.\",\n      \"method\": \"NMR spectroscopy\",\n      \"journal\": \"Nature structural biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — first structure of MafG DNA-binding domain by NMR with functional domain mapping, single study but rigorous structural method\",\n      \"pmids\": [\"11875518\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"MafG forms heterodimers with the CNC-bZIP factor TCF11/LCR-F1/Nrf1; the MafG–TCF11 heterodimer binds a 5'-TGCTgaGTCAT-3' sequence (identical to the NF-E2/ARE/heme-responsive element) with higher affinity than TCF11 alone, yet MafG interferes with TCF11 transactivation in a dose-dependent manner, acting as a repressor when co-expressed with TCF11.\",\n      \"method\": \"Binding-site selection, EMSA, transient transfection reporter assay, in vitro dimerization\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — binding-site selection + EMSA + functional reporter assay, multiple orthogonal methods in one study\",\n      \"pmids\": [\"9421508\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Overexpressed MafG (and MafK) homodimers bind the NQO1 ARE and negatively regulate ARE-mediated NQO1 and GST Ya gene expression and antioxidant induction in HepG2 cells; MafG-Nrf2 heterodimers also repress, whereas Maf-Nrf1 heterodimers fail to bind the NQO1 ARE and show no repressive effect.\",\n      \"method\": \"Transfection reporter assay, EMSA/band-shift and supershift assays in HepG2 cells\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal EMSA + functional reporter, multiple constructs tested in same study\",\n      \"pmids\": [\"11013233\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"MafG (together with Nrf2) forms an EMSA complex (complex X) that binds stress-response elements (StREs) in the heme oxygenase-1 promoter; dominant-negative mutants of both Nrf2 and small Maf (but not other bZIP factors) attenuate cobalt-mediated HO-1 gene activation, placing the Nrf2–MafG heterodimer as the functional unit at the StRE.\",\n      \"method\": \"EMSA with antibody supershift, dominant-negative transfection, luciferase reporter assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — supershift EMSA + dominant-negative functional test + reporter, multiple orthogonal methods\",\n      \"pmids\": [\"11356853\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Nrf2 transcriptionally activates the mafG gene through a conserved ARE (Ic-ARE) in the mafG proximal promoter; Nrf2/MafG heterodimer binds the Ic-ARE in vivo (ChIP) and in vitro; DEM fails to induce mafG in nrf2-null cells, establishing an autoregulatory feedback loop.\",\n      \"method\": \"Luciferase reporter assay, ChIP, gel-shift assay, nrf2-null cells\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP + reporter + null-cell epistasis, multiple orthogonal methods in one study\",\n      \"pmids\": [\"15574414\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"MafG binding kinetics to six MARE-related sequences were quantified by surface plasmon resonance (SPR) imaging on a DNA array; kinetic values correlated well with EMSA, validating SPR imaging as a method for comprehensive TF–DNA interaction analysis and confirming sequence-specific binding affinities of MafG.\",\n      \"method\": \"SPR imaging on double-stranded DNA array, EMSA\",\n      \"journal\": \"Genes to cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro SPR binding assay, single study, primarily methodological but establishes MafG–DNA kinetics\",\n      \"pmids\": [\"15009092\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"MafG is conjugated to SUMO-2/3 in vivo; sumoylation-deficient MafG retains normal heterodimer (p45-dependent) activation but loses transcriptional repression activity in vivo; SUMO-dependent repression by MafG is sensitive to histone deacetylase inhibition, indicating MafG homodimer repression requires SUMO-mediated recruitment of an HDAC-containing repressor complex rather than simple competitive DNA binding.\",\n      \"method\": \"Transgenic mice and cultured cells with wild-type vs. sumoylation-deficient MafG mutant; HDAC inhibitor treatment\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo transgenic + mutagenesis + pharmacological inhibitor, multiple orthogonal methods\",\n      \"pmids\": [\"16738329\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"MafG physically interacts with HIF-1α (identified by yeast two-hybrid, confirmed by SPR and co-localization); MafG knockdown reduces nuclear accumulation of HIF-1α without changing total HIF-1α protein levels, thereby reducing EPO mRNA and HRE-reporter activity, indicating MafG retains HIF-1α in the nucleus to support hypoxic gene activation.\",\n      \"method\": \"Yeast two-hybrid, SPR, nuclear co-localization (nucleolus with NoLS), siRNA knockdown, luciferase reporter, RT-PCR\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Weak — yeast two-hybrid + SPR + KD functional assay, single lab, single study\",\n      \"pmids\": [\"18538669\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Genome-wide ChIP-seq in cells identified co-occupied Nrf2–MafG binding sites enriched for ARE motifs in species-conserved regions; co-occupied sites showed higher enrichment than Nrf2-only sites, and the majority of Nrf2-regulated cytoprotective genes and also glucose metabolism/amino acid transporter genes were located near Nrf2–MafG co-binding sites, demonstrating broad genome-wide cooperative regulation.\",\n      \"method\": \"ChIP-seq for Nrf2 and MafG\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide ChIP-seq for both proteins, bioinformatic validation, single study but rigorous\",\n      \"pmids\": [\"22965115\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"In BRAF(V600E) CRC cells, MAFG is phosphorylated and elevated via BRAF/MEK/ERK signaling; elevated MAFG binds promoters of MLH1 and other CIMP genes and recruits a corepressor complex containing its heterodimeric partner BACH1, the chromatin remodeling factor CHD8, and DNA methyltransferase DNMT3B, leading to CpG hypermethylation and transcriptional silencing of those genes.\",\n      \"method\": \"RNAi screen, ChIP-seq, co-immunoprecipitation, pharmacological MEK/ERK inhibition, CRC cell lines and tumor specimens\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — RNAi screen + ChIP + reciprocal Co-IP + cell lines and tumor validation, multiple orthogonal methods replicated in primary tumors\",\n      \"pmids\": [\"25219500\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"MAFG is an FXR target gene; hepatic MAFG overexpression represses bile acid synthesis genes (Cyp7a1, Cyp8b1) and alters biliary bile acid composition; MafG(+/-) haploinsufficiency de-represses these same genes with concordant bile acid changes; ChIP-seq identified functional MAFG response elements in bile acid metabolism gene regulatory regions.\",\n      \"method\": \"Gain-of-function (overexpression), loss-of-function (MafG+/- mice), ChIP-seq, bile acid profiling\",\n      \"journal\": \"Cell metabolism\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — complementary gain- and loss-of-function in vivo + ChIP-seq, multiple orthogonal methods\",\n      \"pmids\": [\"25651182\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"MafG forms heterodimers with FosB in the nucleus; decreasing extracellular pH from 7.40 to 6.80 enhances MafG–FosB dimerization and augments binding of the heterodimer to AP-1 consensus sequences, leading to increased MMP-1 transcription.\",\n      \"method\": \"Immunofluorescence co-localization, co-immunoprecipitation/protein binding, EMSA, RT-PCR\",\n      \"journal\": \"Journal of cellular physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/EMSA with functional reporter, single lab\",\n      \"pmids\": [\"15828020\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"A tethered Nrf2–MafG heterodimer (T-N2G), introduced into small Maf triple-knockout fibroblasts, specifically activates Nrf2 target cytoprotective genes (but not Nrf1 targets such as proteasome subunit genes) and preferentially binds CNC-sMaf binding element (CsMBE) motifs genome-wide, providing direct evidence that the Nrf2–MafG heterodimer is sufficient for ARE/CsMBE-dependent transcriptional activation.\",\n      \"method\": \"Tethered dimer construct in sMaf triple-KO cells, genome-wide ChIP-seq, gene expression analysis\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — unique reconstitution approach in null background + genome-wide binding, rigorous genetic controls\",\n      \"pmids\": [\"31383749\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"A tethered Nrf1–MafG heterodimer (T-N1G) specifically activates proteasome subunit genes and genes involved in ER-associated degradation, chaperone, and ubiquitin-mediated degradation pathways through CsMBE binding, demonstrating that Nrf1–MafG heterodimer has a distinct target gene repertoire from Nrf2–MafG; under strong induction, Nrf1 can also activate canonical Nrf2 target genes.\",\n      \"method\": \"Tethered dimer construct in sMaf triple-KO cells, genome-wide ChIP-seq, gene expression analysis\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — reconstitution in null background + genome-wide binding, same rigorous system as companion Nrf2-MafG study\",\n      \"pmids\": [\"35129372\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In EAE and multiple sclerosis astrocytes, increased MAFG expression cooperates with MAT2α to promote DNA methylation and repress antioxidant/anti-inflammatory transcriptional programs; GM-CSF signaling in astrocytes drives MAFG and MAT2α expression and pro-inflammatory transcriptional modules; in vivo CRISPR-Cas9 perturbation of MAFG modulates CNS pathology in EAE.\",\n      \"method\": \"Single-cell RNA-seq, Ribotag RNA profiling, ATAC-seq, ChIP-seq, genome-wide DNA methylation analysis, in vivo CRISPR-Cas9 genetic perturbation\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal genomic methods + in vivo CRISPR perturbation, replicated across EAE and MS patient samples\",\n      \"pmids\": [\"32051591\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"MAFG signaling during diet-induced obesity represses hepatic lncRNA expression; silencing Mafg in mouse hepatocytes and obese mice elicits a fasting-like gene expression profile, improves glucose metabolism, de-represses lncRNAs, and impairs mTOR activation, placing MAFG as a nutrient-sensitive transcriptional repressor in hepatic glucose metabolism.\",\n      \"method\": \"Gain-of-function (overexpression), RNAi-mediated knockdown in mouse hepatocytes and obese mice, global cistrome analysis, gene expression profiling\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — complementary gain/loss-of-function in vivo + cistrome analysis, multiple orthogonal methods\",\n      \"pmids\": [\"32005828\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"LCA (lithocholic acid) activates MAFG expression through AP-1, NF-κB, and E-box sites in its promoter; MAT2A overexpression increases MAFG promoter activity whereas MAT1A decreases it; MAFG directly interacts with MATα1 and occupies E-box elements to repress transcription; SAMe and UDCA reduce MAFG expression by shared and distinct mechanisms.\",\n      \"method\": \"Transfection reporter assay, EMSA, ChIP, siRNA knockdown, overexpression, mouse cholestasis models\",\n      \"journal\": \"Gastroenterology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — EMSA + ChIP + reporter + in vivo models, multiple orthogonal methods in one study\",\n      \"pmids\": [\"29733835\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"MafG physically interacts with non-muscle myosin heavy chain IIa (MYH9) to form a transcriptional complex that activates LCN2 expression; site-directed mutation of the MARE motif in the LCN2 promoter blocks MafG binding; MafG knockdown increases hepatic stellate cell ferroptosis and re-expression of LCN2 in MafG-knockdown HSCs restores ferroptosis resistance; HSC-specific AAV6-mediated MafG knockdown promotes ferroptosis and alleviates liver fibrosis in BDL mice.\",\n      \"method\": \"Co-immunoprecipitation, site-directed mutagenesis of MARE motif, ChIP, siRNA/overexpression, AAV-mediated in vivo knockdown, BDL mouse model\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP + mutagenesis + ChIP + in vivo AAV KD, multiple orthogonal methods\",\n      \"pmids\": [\"38871948\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"Germline ablation of mafG in mice results in impaired platelet formation with megakaryocyte proliferation defects and behavioral abnormalities; mafK-null mice are phenotypically normal; compound mafG/mafK knockouts show synthetic lethality and exacerbated erythroid and megakaryocytic deficiencies, demonstrating in vivo functional redundancy between small Maf proteins.\",\n      \"method\": \"Gene targeting (null alleles replacing coding sequences with lacZ), phenotypic analysis of KO mice\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — mouse KO with defined megakaryocytic and behavioral phenotype, replicated with compound KO\",\n      \"pmids\": [\"9679061\", \"10716933\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In melanoma, YAP inactivation (triggered by soft matrix/low mechanical force via integrin β8–RhoGDI1–RhoA pathway) relieves YAP-mediated inhibition of MAFG, allowing MAFG to transactivate stemness genes NANOG, SOX2, and NESTIN; MAFG inactivation also restores β8 expression, forming a closed mechanical feedback loop.\",\n      \"method\": \"Gene silencing, overexpression, mechanotransduction assays (soft vs. stiff matrices), reporter assays\",\n      \"journal\": \"Research (Washington, D.C.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — loss-of-function with defined phenotype and pathway placement, single lab, single study\",\n      \"pmids\": [\"37614365\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MafG forms a functional heterodimer with Bach1 that directly engages the Lcn2 promoter and drives its transcriptional activation; MafG overexpression promotes ferroptosis via iron accumulation and lipid peroxidation in alveolar epithelial cells, and MafG knockdown (via AAV-shMafG) mitigates lung injury and improves survival in sepsis models; the natural compound Anemoside B4 was identified as a MafG inhibitor by SPR.\",\n      \"method\": \"Co-immunoprecipitation, mass spectrometry, luciferase reporter assay, siRNA/AAV knockdown, in vivo sepsis model (CLP), SPR\",\n      \"journal\": \"Free radical biology & medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — Co-IP + reporter + in vivo KD, single lab, single study\",\n      \"pmids\": [\"41475687\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"MAFG expression is upregulated in spinal cord injury (SCI) astrocytes; MAFG binds the CRYAB promoter and promotes its methylation (involving DNMT3b); MAFG silencing inhibits A1 astrocyte activation and neuroinflammation and improves functional recovery after SCI; 5-Aza (methylation inhibitor) further inhibited A1 activation, while DNMT3b overexpression reversed MAFG-silencing effects.\",\n      \"method\": \"Rat SCI model, ACM/LPS astrocyte model, siRNA knockdown, RT-PCR, Western blot, immunofluorescence, functional behavior scores\",\n      \"journal\": \"Immunity, inflammation and disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — KD with defined phenotype + pharmacological/genetic epistasis on CRYAB methylation, single lab\",\n      \"pmids\": [\"41555187\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"In bladder cancer cells, MAFG transcriptionally activates MAFG-AS1 expression; MAFG-AS1 in turn recruits histone acetyltransferase p300 to promote H3K27ac at the MAFG genomic locus, forming a positive feedback loop.\",\n      \"method\": \"ChIP, luciferase reporter assay, siRNA/overexpression, co-immunoprecipitation in bladder cancer cells\",\n      \"journal\": \"Science bulletin\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — ChIP + reporter for MAFG side of feedback, single lab, single study; note this paper primarily concerns lncRNA MAFG-AS1\",\n      \"pmids\": [\"36654385\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MAFG directly activates METTL14 expression in choroidal melanoma; MAFG-METTL14-SCD1 axis promotes lipid remodeling and membrane fluidity driving metastasis; MAFG was shown to transcriptionally activate METTL14 as part of this axis.\",\n      \"method\": \"Multiplex immunohistochemistry, transcriptomics, lipidomics, METTL14 silencing, mechanistic pathway validation\",\n      \"journal\": \"Journal of experimental & clinical cancer research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, limited mechanistic detail in abstract regarding MAFG's direct transcriptional activity on METTL14\",\n      \"pmids\": [\"41316357\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"MAFG and NFE2L1 (NRF1) bind to a locus (locus 22) in the PD-L1 super-enhancer to drive PD-L1 expression; silencing MAFG reduces BRD4 binding and chromatin loop formation at the PD-L1 locus but has minimal effect on H3K27Ac; MAFG/NFE2L1-silenced cells fail to upregulate PD-L1 in response to LPS and cannot escape T cell-mediated killing.\",\n      \"method\": \"CRISPR-Cas9 saturated screening, genetic silencing, ChIP for BRD4/H3K27Ac, 3D chromatin conformation (loop formation), T cell killing assay\",\n      \"journal\": \"Oncogenesis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — CRISPR screen + ChIP + functional immune assay, single lab, single study\",\n      \"pmids\": [\"37985752\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"MAFG directly interacts with MITF in melanoma cells; this MAFG–MITF complex redirects MITF genomic occupancy and modulates MITF-governed transcriptional programs, promoting melanoma dedifferentiation and phenotype switching to a more stem-like state; genetic perturbation in vitro and in vivo shows MAFG is required for the transition from nevi to melanoma.\",\n      \"method\": \"Co-immunoprecipitation, ChIP/genomic occupancy analysis, overexpression, genetic KO/KD, xenograft models, genetic mouse models of melanoma\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — Co-IP + ChIP occupancy + in vitro and in vivo genetic perturbation in multiple model systems, peer-reviewed replication of preprint findings\",\n      \"pmids\": [\"42168173\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"In osteosarcoma cells, MAFG forms a heterodimer with Nrf2 and promotes binding to the ARE to activate Nrf2 target genes; MAFG silencing or knockout inhibits OS cell growth, proliferation, and migration while inducing oxidative injury and apoptosis; miR-4660 directly binds the 3'UTR of MAFG mRNA to suppress MAFG expression and OS progression.\",\n      \"method\": \"MAFG siRNA/KO, overexpression, 3'UTR luciferase assay, in vivo xenograft (subcutaneous and orthotopic)\",\n      \"journal\": \"Molecular therapy. Nucleic acids\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — KO + overexpression + in vivo xenograft, single lab; Nrf2 heterodimer claim supported by prior literature\",\n      \"pmids\": [\"33868783\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"MAFG interacts with METTL11A protein; METTL11A prevents MAFG degradation through K6 methylation modification; MAFG and NRF2 together bind the promoter region of NPL4 to promote its transcription, forming a METTL11A-MAFG-NPL4 positive feedback loop that promotes bladder cancer cell proliferation.\",\n      \"method\": \"Co-immunoprecipitation, ChIP, luciferase reporter assay, transcriptome sequencing, in vitro and in vivo proliferation assays\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Weak — Co-IP + ChIP + reporter, single lab, single study\",\n      \"pmids\": [\"40171788\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"MAFG binds the HMOX1 (HO-1) promoter and represses its transcription in astrocytes; MAFG knockdown in a mouse CUMS depression model reduces A1 astrocyte-mediated neuroinflammation via restoration of HMOX1 expression; HMOX1 knockdown recapitulates MAFG-driven neuroinflammation.\",\n      \"method\": \"ChIP (MAFG binding to HMOX1 promoter), siRNA knockdown, CUMS mouse model, RT-PCR, Western blot\",\n      \"journal\": \"Brain research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Weak — ChIP + KD epistasis in vivo, single lab, single study\",\n      \"pmids\": [\"38977234\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MAFG is a small bZIP transcription factor that functions exclusively as an obligate dimerization partner: as a homodimer it acts as a transcriptional repressor (requiring SUMO-2/3-mediated recruitment of HDAC-containing complexes for active repression), while as a heterodimer with CNC-family proteins (Nrf2, Nrf1, p45 NF-E2) it activates ARE/CsMBE-dependent cytoprotective, antioxidant, and metabolic genes; with Bach proteins it represses target loci; in cancer contexts, BRAF/MEK/ERK-driven phosphorylation elevates MAFG levels, which then recruits BACH1–CHD8–DNMT3B corepressor complexes to silence tumor suppressor genes via CpG methylation; FXR activation induces MAFG to repress bile acid synthesis genes; in astrocytes, GM-CSF signaling elevates MAFG which cooperates with MAT2α to drive DNA methylation and pro-inflammatory programs; and in melanoma MAFG dimerizes with MITF to redirect its genomic occupancy and promote phenotype switching toward dedifferentiation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MAFG is a small bZIP transcription factor that functions as an obligate dimerization module, lacking an intrinsic transactivation domain and dictating the DNA-binding specificity and regulatory output of its partners through its basic region and Maf extended homology region [#0]. As a homodimer it acts as a transcriptional repressor that depends on SUMO-2/3 conjugation to recruit an HDAC-containing corepressor complex, rather than on simple competitive occupancy of DNA [#6]. As a heterodimer with CNC-family factors it confers sequence-specific activation at ARE/CsMBE elements: tethered Nrf2\\u2013MafG and Nrf1\\u2013MafG dimers reconstituted in small-Maf-null cells are each sufficient to drive distinct cytoprotective programs\\u2014antioxidant/metabolic genes for Nrf2\\u2013MafG and proteasome/ERAD/degradation genes for Nrf1\\u2013MafG\\u2014both through CsMBE binding [#12, #13]. Genome-wide, Nrf2\\u2013MafG co-occupancy marks the bulk of Nrf2-regulated cytoprotective and metabolic loci, and MAFG itself is an Nrf2 target gene, establishing an autoregulatory feedback loop [#4, #8]. MAFG also serves as a tunable transcriptional effector in metabolism and disease: it is an FXR target that represses bile-acid synthesis genes (Cyp7a1, Cyp8b1) [#10], a nutrient-responsive repressor of hepatic lncRNAs that restrains glucose metabolism and mTOR activation [#15], and in BRAF(V600E) colorectal cancer it is phosphorylated and stabilized by BRAF/MEK/ERK signaling to recruit a BACH1\\u2013CHD8\\u2013DNMT3B corepressor complex that silences MLH1 and other CIMP genes by CpG hypermethylation [#9]. In melanoma, MAFG dimerizes with MITF to redirect MITF genomic occupancy and drive dedifferentiation and phenotype switching, and is required for the nevus-to-melanoma transition [#25]. Genetic ablation in mice causes defective platelet/megakaryocyte formation and behavioral abnormalities, with synthetic lethality and erythroid/megakaryocytic deficiency in combination with mafK, demonstrating functional redundancy among small Maf proteins [#18].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Established the foundational principle that MafG is not an autonomous activator but a dimerization partner that modulates a CNC factor, repressing TCF11/Nrf1 transactivation while increasing heterodimer DNA affinity.\",\n      \"evidence\": \"Binding-site selection, EMSA, and reporter assays with MafG\\u2013TCF11 heterodimers\",\n      \"pmids\": [\"9421508\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve whether repression reflects sequestration or active corepressor recruitment\", \"Did not address other CNC partners\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"In vivo gene ablation defined the physiological requirement for MafG in megakaryocyte/platelet biology and revealed redundancy with MafK, distinguishing essential from compensable small-Maf functions.\",\n      \"evidence\": \"Single and compound mafG/mafK null mice with phenotypic analysis\",\n      \"pmids\": [\"9679061\", \"10716933\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not identify the dimer partners driving each phenotype\", \"Behavioral abnormality mechanism unexplained\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"The NMR structure of the DNA-binding domain explained how the basic region plus Maf extended homology region encode binding specificity, providing the structural basis for partner-dependent site selection.\",\n      \"evidence\": \"NMR solution structure of MafG residues 1-76\",\n      \"pmids\": [\"11875518\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structure of a heterodimer bound to DNA\", \"Did not address how partners reshape specificity\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Defined MafG as the obligate partner of Nrf2 at the heme oxygenase/StRE and NQO1 ARE and showed MafG is itself an Nrf2 target, revealing an autoregulatory antioxidant feedback circuit; reciprocal EMSA distinguished repressive (homodimer, Nrf2 heterodimer) from inactive (Nrf1) configurations on the NQO1 ARE.\",\n      \"evidence\": \"Supershift EMSA, dominant-negative tests, ChIP, reporter assays, and nrf2-null cells\",\n      \"pmids\": [\"11013233\", \"11356853\", \"15574414\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not separate cooperative activation from repression mechanistically\", \"In vivo physiological weighting of the feedback loop unaddressed\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Resolved the mechanism of homodimer repression, showing it requires SUMO-2/3 conjugation to recruit an HDAC-dependent corepressor rather than passive DNA competition, decoupling repression from activation activity.\",\n      \"evidence\": \"Transgenic mice and cells with wild-type vs sumoylation-deficient MafG plus HDAC inhibition\",\n      \"pmids\": [\"16738329\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity of the recruited HDAC complex not defined\", \"SUMO ligase and deconjugation control unknown\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Genome-wide mapping demonstrated that Nrf2\\u2013MafG co-occupancy, not Nrf2 alone, defines the functional cytoprotective and metabolic cistrome, generalizing the heterodimer principle to the whole genome.\",\n      \"evidence\": \"ChIP-seq for Nrf2 and MafG with motif analysis\",\n      \"pmids\": [\"22965115\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not test sufficiency of the heterodimer in isolation\", \"Did not distinguish Nrf1 vs Nrf2 contributions at shared sites\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Tethered-dimer reconstitution in small-Maf-null cells provided direct proof that the Nrf2\\u2013MafG heterodimer is sufficient for CsMBE/ARE-dependent activation of cytoprotective genes.\",\n      \"evidence\": \"Tethered Nrf2\\u2013MafG construct in sMaf triple-KO fibroblasts with ChIP-seq\",\n      \"pmids\": [\"31383749\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not address endogenous stoichiometry of free vs tethered dimers\", \"Repression activity not modeled in this system\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"An analogous tethered Nrf1\\u2013MafG dimer showed that partner identity assigns MafG to a distinct proteostasis target repertoire, establishing how one small Maf diversifies output across CNC partners.\",\n      \"evidence\": \"Tethered Nrf1\\u2013MafG construct in sMaf triple-KO cells with ChIP-seq and expression profiling\",\n      \"pmids\": [\"35129372\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of target discrimination between Nrf1 and Nrf2 dimers unresolved\", \"Cellular conditions that bias partner choice unknown\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Linked MafG to oncogenic signaling and epigenetic silencing, showing BRAF/MEK/ERK-driven phosphorylation elevates MAFG to recruit a BACH1\\u2013CHD8\\u2013DNMT3B complex that hypermethylates and silences CIMP genes including MLH1.\",\n      \"evidence\": \"RNAi screen, ChIP-seq, reciprocal Co-IP, MEK/ERK inhibition in CRC lines and tumors\",\n      \"pmids\": [\"25219500\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Phosphorylation sites and how they control stability not fully mapped\", \"Generality beyond BRAF-mutant CRC untested here\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Defined MafG as an FXR-induced metabolic repressor controlling bile-acid synthesis, extending its repressor role into nuclear-receptor-driven hepatic physiology.\",\n      \"evidence\": \"Hepatic gain/loss-of-function in mice plus ChIP-seq and bile-acid profiling\",\n      \"pmids\": [\"25651182\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Dimer partner mediating bile-acid gene repression not identified\", \"Corepressor machinery at these loci undefined\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Two studies expanded MafG's repressor role into nutrient sensing and DNA-methylation-coupled inflammation: hepatic MafG restrains lncRNAs and mTOR during obesity, and astrocyte MafG cooperates with MAT2\\u03b1 to methylate and repress anti-inflammatory programs in CNS autoimmunity.\",\n      \"evidence\": \"Cistrome/expression profiling with hepatocyte and obese-mouse perturbation; scRNA-seq, ATAC-seq, ChIP-seq, methylation analysis, and in vivo CRISPR in EAE/MS\",\n      \"pmids\": [\"32005828\", \"32051591\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Upstream signals coupling MafG to MAT2\\u03b1/SAM methyl-donor flux only partly defined\", \"Dimer partners at repressed metabolic loci not identified\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Demonstrated that MafG can rewire a master lineage factor by directly binding MITF, redirecting its occupancy to drive melanoma dedifferentiation and the nevus-to-melanoma transition.\",\n      \"evidence\": \"Co-IP, ChIP occupancy, and genetic perturbation in melanoma cells, xenografts, and mouse models\",\n      \"pmids\": [\"42168173\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the MAFG\\u2013MITF interaction unknown\", \"How MAFG levels are set in melanoma not fully resolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how MafG's choice among many partners (CNC factors, Bach1, MITF, FosB, MYH9) is governed in a given cell, and how its dual activator/repressor outputs and post-translational control are coordinated across tissues.\",\n      \"evidence\": \"No single study in the corpus integrates partner selection, modification state, and output across contexts\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No mechanism assigning partner choice to cell state\", \"No unified model of phosphorylation/SUMO/methylation control over MafG abundance and activity\", \"Most non-CNC partner interactions rest on single Co-IP studies\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1, 2, 8, 12, 13, 10, 9]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [0, 1, 5, 8]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 2, 12, 13, 25]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [6, 7, 11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953897\", \"supporting_discovery_ids\": [2, 3, 4, 8, 12]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [1, 8, 12, 13]},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [10, 15]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [9, 14, 25]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"NFE2L2\", \"NFE2L1\", \"BACH1\", \"CHD8\", \"DNMT3B\", \"MITF\", \"MAT2A\", \"HIF1A\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}