{"gene":"NFYB","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":1987,"finding":"HAP3 (yeast ortholog of NFYB) and HAP2 bind interdependently to the CCAAT-containing UAS2 of CYC1; neither protein binds DNA alone, and binding of either is abolished when the complementary HAP gene is mutated, demonstrating that they form a heteromeric DNA-binding complex.","method":"Nondenaturing PAGE gel shift with beta-galactosidase and LexA fusion proteins; methylation interference footprinting; in vitro DNA binding with yeast extracts","journal":"Cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with tagged fusions, footprinting, replicated across multiple labs","pmids":["2826015"],"is_preprint":false},{"year":1988,"finding":"HAP2 and HAP3 associate with each other in the absence of DNA to form a multisubunit activation complex, as shown by co-purification through four chromatographic steps.","method":"Co-purification of LexA-HAP2 and HAP3-beta-galactosidase fusion proteins through four chromatographic steps; DNA binding activity co-purified with the complex","journal":"Science","confidence":"High","confidence_rationale":"Tier 1 / Strong — biochemical co-purification with tagged fusions demonstrating pre-formed complex independent of DNA","pmids":["2832951"],"is_preprint":false},{"year":1988,"finding":"HAP3 encodes a 144-amino acid protein essential for UAS2 activity and growth on non-fermentable carbon sources; the 86-amino acid ORF in the antisense transcript is not involved in UAS2 activity.","method":"Chromosomal disruption, site-directed mutagenesis, in vivo complementation, reporter assays","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic loss-of-function with defined phenotypic readout, mutagenesis, multiple orthogonal experiments","pmids":["2832732"],"is_preprint":false},{"year":1989,"finding":"HAP4 is a third subunit of the HAP2/HAP3 DNA-binding complex at UAS2; HAP4 is required for detectable HAP2/HAP3 binding in vitro and provides the principal transcriptional activation domain to the complex.","method":"Genetic analysis; in vitro DNA binding; deletion analysis of HAP4; GAL4 activation domain swap","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro binding assay plus mutagenesis plus genetic epistasis, replicated","pmids":["2676721"],"is_preprint":false},{"year":1990,"finding":"Mammalian CBF-A (NF-YB) is the 'A' chain of the CCAAT-binding factor (CBF) heteromer, and its deduced amino acid sequence shares remarkable identity (~90 residues) with yeast HAP3, establishing evolutionary conservation of the NFYB subunit.","method":"Protein purification by DNA affinity chromatography; tryptic peptide sequencing; cDNA cloning and in vitro transcription/translation","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — biochemical purification to homogeneity, sequence identity confirmed, in vitro translation product confirmed","pmids":["2266139"],"is_preprint":false},{"year":1993,"finding":"Short regions of HAP3 (NFYB ortholog) form a hybrid DNA-binding domain with HAP2; a seven-amino-acid region in HAP3 is critical for DNA binding, and HAP3 mutations suppress multiple HAP2 DNA-binding domain mutations, indicating direct structural cooperation.","method":"Genetic mutational analysis; in vitro DNA binding; intragenic suppressor analysis","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — mutagenesis with suppressor genetics, multiple alleles tested","pmids":["8223474"],"is_preprint":false},{"year":1995,"finding":"Rat CBF-C (NF-YC) is required together with CBF-A (NF-YB) and CBF-B (NF-YA) to form a CBF-DNA complex; CBF-A and CBF-C interact directly with each other, and CBF-B does not interact with either subunit individually but associates with the CBF-A/CBF-C heterodimer.","method":"Recombinant protein expression; in vitro EMSA/DNA binding reconstitution; protein-protein interaction assays; cross-complementation with yeast HAP2/HAP3","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — full reconstitution of heterotrimeric complex with recombinant proteins, multiple orthogonal assays","pmids":["7878029"],"is_preprint":false},{"year":1996,"finding":"CBF-A (NF-YB) and CBF-C (NF-YC) interact through their histone fold motifs to form a heterodimer; this heterodimer generates a tridentate interaction surface that binds CBF-B (NF-YA) to form the heterotrimeric CBF; the evolutionarily conserved histone-fold segment of CBF-C is necessary for DNA complex formation.","method":"Cross-linking; immunoprecipitation; mutational analysis; yeast two-hybrid; in vitro DNA binding assays","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — reciprocal interaction mapping with mutagenesis, multiple orthogonal methods, two-hybrid plus biochemical validation","pmids":["8754798"],"is_preprint":false},{"year":1997,"finding":"NF-YB and NF-YC each interact directly with TBP in solution; short domains adjacent to their histone fold motifs are necessary for TBP binding; a fraction of NF-YB associates with TFIID (in the absence of NF-YA); TBP mutants in the HS2 helix defective in NC2 binding are also unable to bind NF-YB and NF-YC.","method":"Immunopurification of holo-TFIID; sedimentation velocity centrifugation; in vitro protein-protein interaction assays with truncation/domain mutants","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct interaction assays with domain mapping, multiple orthogonal biochemical methods in single study","pmids":["9153318"],"is_preprint":false},{"year":2002,"finding":"The crystal structure of the NF-YB/NF-YC subcomplex shows that their core domains interact through histone fold motifs closely related to H2A/H2B and NC2alpha/NC2beta; the alphaC helix of NF-YC is important both for NF-Y trimerization and as a target for regulatory proteins such as MYC and p53.","method":"X-ray crystallography; structural modeling of NF-YC/NF-YB with DNA and full NF-Y/CCAAT complex","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure determination with functional modeling, defines molecular basis of subunit interaction","pmids":["12401788"],"is_preprint":false},{"year":2002,"finding":"MADS-box protein OsMADS18 forms a ternary complex with rice NF-YB (OsNF-YB1) via the MADS and I regions; mouse NF-YB also associates with OsMADS18 as an NF-YB/NF-YC dimer; OsNF-YB1 can heterodimerize with NF-YC but cannot trimerize with NF-YA, precluding CCAAT binding; mutation of Asp99 in the HFM alpha2-helix of OsNF-YB1 to the conserved Ser recovers NF-YA interaction but not DNA binding.","method":"Yeast two-hybrid screening; in vitro and in vivo protein-protein interaction assays; site-directed mutagenesis","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal two-hybrid plus in vitro/in vivo assays, single lab, plant ortholog with mammalian NF-YB confirmation","pmids":["11971906"],"is_preprint":false},{"year":2010,"finding":"Dysbindin physically interacts with NF-YB in mouse brain; this complex binds the CCAAT motif at the MARCKS promoter and regulates MARCKS transcription; knockdown of either Dysbindin or NF-YB increases MARCKS expression.","method":"Yeast two-hybrid screening; co-immunoprecipitation; chromatin immunoprecipitation; reporter assay; DNA chip gene expression profiling","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — co-IP plus ChIP plus reporter assay, single lab, multiple orthogonal methods","pmids":["20098743"],"is_preprint":false},{"year":2011,"finding":"IER5 reduces Cdc25B mRNA expression through direct binding to the Cdc25B promoter and mediates transcriptional repression via release of NF-YB and p300 co-activator, inhibiting AML progenitor cell proliferation.","method":"Reporter assays; chromatin immunoprecipitation; gene knockdown/overexpression; colony formation assay","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — ChIP plus reporter assay plus functional rescue, single lab","pmids":["22132193"],"is_preprint":false},{"year":2015,"finding":"NFYB is a direct transcriptional target of E2F1; NFYB knockdown enhances E2F1-induced apoptosis, indicating that the NFYB/E2F1 joint transcriptional program has a pro-survival function.","method":"Genome-wide expression analysis; NFYB knockdown; apoptosis assays; E2F1 overexpression","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — genome-wide analysis with functional knockdown, single lab, defined phenotypic readout","pmids":["26039627"],"is_preprint":false},{"year":2017,"finding":"NFYB transactivates the E2F1 gene in oxaliplatin-resistant colorectal cancer cells; the NFYB-E2F1-CHK1 axis suppresses oxaliplatin-induced apoptosis and maintains tumorigenicity in vitro and in vivo.","method":"Gene knockdown/overexpression; transcriptome profiling; in vitro and in vivo phenotype experiments; reporter assays","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — functional knockdown/OE with defined phenotype plus transcriptomics, single lab","pmids":["29203250"],"is_preprint":false},{"year":2020,"finding":"C. elegans NFYB-1 is a crucial regulator of mitochondrial function; its loss leads to perturbed mitochondrial gene expression, reduced oxygen consumption, mitochondrial fragmentation, disrupted mitochondrial stress pathways, and decreased cardiolipin levels. NFYB-1 acts as a repressor of lysosomal prosaposin; limiting prosaposin restores cardiolipin production and mitochondrial function in nfyb-1 mutants.","method":"RNAi screens; multi-omics analysis (transcriptomics, metabolomics); oxygen consumption assays; microscopy of mitochondrial morphology; cardiolipin supplementation rescue","journal":"Nature metabolism","confidence":"High","confidence_rationale":"Tier 2 / Strong — multi-omics with multiple orthogonal functional assays and genetic rescue experiments, replicated in C. elegans model","pmids":["32694663"],"is_preprint":false},{"year":2021,"finding":"IER5 represses Cdc25B transcription in irradiated HeLa cells via the NF-YB binding site on the Cdc25B promoter; IER5 binds the Cdc25B promoter and induces release of the coactivator p300 through interaction with NF-YB.","method":"Dual-luciferase reporter assays; site-directed mutagenesis of promoter elements; chromatin immunoprecipitation (ChIP); irradiation model","journal":"Toxicology research","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — ChIP plus reporter assay plus mutagenesis, single lab, confirms NF-YB as the relevant promoter element","pmids":["34484679"],"is_preprint":false},{"year":2021,"finding":"NFYB can bind to the STK33 promoter and promote STK33 expression, thereby activating the Hedgehog signaling pathway and promoting cisplatin resistance in DLBCL cells.","method":"Bioinformatics prediction; luciferase reporter assay; gene knockdown; cell sensitivity assays","journal":"Leukemia research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, reporter assay without direct ChIP confirmation, limited mechanistic follow-up","pmids":["34536775"],"is_preprint":false},{"year":2022,"finding":"H19 lncRNA recruits NFYB to the MBTD1 promoter to activate MBTD1 transcription, promoting doxorubicin resistance in lymphoma cells; H19 increases MBTD1 expression in a NFYB-dependent manner without altering NFYB levels.","method":"Luciferase reporter assay; ChIP-qPCR; gene knockdown and overexpression; in vitro and in vivo growth assays","journal":"Molecular biotechnology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — ChIP-qPCR plus reporter plus functional rescue, single lab","pmids":["36434485"],"is_preprint":false},{"year":2023,"finding":"NFYB activates HDAC5 transcription by binding to the HDAC5 promoter; HDAC5 in turn inhibits SHMT2 expression, reducing glycolysis and increasing TMZ sensitivity in GBM cells.","method":"Chromatin immunoprecipitation; dual-luciferase reporter assay; gene overexpression/knockdown; glucose uptake and lactate production assays; proliferation and apoptosis assays","journal":"Journal of neuropathology and experimental neurology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — ChIP plus reporter plus functional rescue assays, single lab, multiple cellular readouts","pmids":["37742129"],"is_preprint":false},{"year":2024,"finding":"Coptisine downregulates E2F7 in HCC by inhibiting E2F4/NF-YA/NF-YB transcription factor activity at the E2F7 promoter, as confirmed by promoter fragmentation experiments and ChIP.","method":"Promoter fragmentation experiments; chromatin immunoprecipitation; RNA-Seq; in vitro and in vivo HCC growth assays","journal":"Chemico-biological interactions","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — ChIP plus promoter analysis, single lab, demonstrates NF-YB participation in E2F7 promoter complex","pmids":["38795876"],"is_preprint":false},{"year":2025,"finding":"NFYB knockout combined with menin-MLL1 inhibition causes significantly increased HCC cell death; menin inhibition increases chromatin accessibility at sites not bound by menin-MLL1 that are associated with NF-Y pioneer factor recruitment, placing NFYB in a cooperative oncogenic gene regulation pathway with menin-MLL1.","method":"CRISPR/Cas9 screen; epigenome-focused CRISPR library screen in 2D and 3D HCC cell lines; chromatin accessibility assays; menin inhibitor (SNDX-5613) treatment","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — CRISPR functional screen with chromatin assays, preprint, single lab","pmids":["bio_10.1101_2025.04.05.647381"],"is_preprint":true}],"current_model":"NFYB (NF-YB/CBF-A/HAP3) is the histone fold domain-containing subunit of the evolutionarily conserved heterotrimeric NF-Y transcription factor complex: it dimerizes with NF-YC via histone fold motifs, and this dimer recruits NF-YA to form the full trimer that binds CCAAT promoter elements; it also contacts TBP/TFIID to facilitate transcription initiation, acts as a transcriptional activator of target genes including E2F1, HDAC5, STK33, and MBTD1, and in C. elegans represses lysosomal prosaposin to maintain mitochondrial cardiolipin levels and organismal longevity."},"narrative":{"mechanistic_narrative":"NFYB (NF-YB/CBF-A/HAP3) is the histone-fold subunit of the evolutionarily conserved heterotrimeric NF-Y/CCAAT-binding transcription factor, a complex first defined in yeast where HAP3 and HAP2 bind interdependently to the CCAAT element of CYC1 and pre-assemble into a multisubunit complex independent of DNA [PMID:2826015, PMID:2832951]. The mammalian subunit CBF-A is the direct ortholog of HAP3, with a deeply conserved core [PMID:2266139]. NFYB heterodimerizes with NF-YC through their histone-fold motifs, generating a tridentate surface that recruits NF-YA to form the trimer competent for CCAAT-element binding [PMID:7878029, PMID:8754798]; the crystal structure of the NF-YB/NF-YC subcomplex shows these histone folds are closely related to H2A/H2B and NC2 [PMID:12401788]. NFYB additionally contacts the general transcription machinery, interacting directly with TBP and associating with TFIID to couple CCAAT recognition to transcription initiation [PMID:9153318]. Through this promoter-binding activity NFYB acts as a transcriptional activator across diverse target genes, transactivating E2F1 and contributing to a pro-survival, chemoresistance-promoting program in cancer cells [PMID:26039627, PMID:29203250], and binding the promoters of HDAC5, MBTD1, and STK33 in additional resistance contexts [PMID:36434485, PMID:37742129]. Its recruitment and output are modulated by partner proteins including Dysbindin at the MARCKS promoter [PMID:20098743] and IER5, which represses Cdc25B by triggering release of the p300 coactivator from NF-YB [PMID:22132193, PMID:34484679]. Beyond its transcriptional role, the C. elegans ortholog NFYB-1 maintains mitochondrial function and cardiolipin levels by repressing lysosomal prosaposin [PMID:32694663].","teleology":[{"year":1988,"claim":"Established that the NFYB ortholog HAP3 is an essential gene product that cannot bind CCAAT DNA alone but must partner with HAP2, defining NF-Y as an obligate heteromeric DNA-binding factor.","evidence":"Gel-shift, footprinting, and chromosomal disruption/complementation with tagged HAP2/HAP3 fusions in yeast","pmids":["2826015","2832732"],"confidence":"High","gaps":["Did not resolve which residues mediate the protein-protein interaction","Mammalian subunit composition not yet defined"]},{"year":1988,"claim":"Showed that HAP2 and HAP3 pre-assemble into a stable complex in the absence of DNA, indicating subunit dimerization precedes DNA engagement.","evidence":"Co-purification of LexA-HAP2 and HAP3-beta-galactosidase fusions through four chromatographic steps","pmids":["2832951"],"confidence":"High","gaps":["Did not identify additional subunits required for full activation","Structural basis of association unknown"]},{"year":1990,"claim":"Connected the yeast and mammalian systems by demonstrating that mammalian CBF-A is the histone-fold-bearing ortholog of HAP3, establishing evolutionary conservation of the NFYB subunit.","evidence":"DNA affinity purification, tryptic peptide sequencing, and cDNA cloning of mammalian CBF","pmids":["2266139"],"confidence":"High","gaps":["Full mammalian trimer composition not yet reconstituted","Conserved residues mediating dimerization not mapped"]},{"year":1996,"claim":"Defined the assembly logic of the mammalian trimer: NF-YB and NF-YC dimerize via histone-fold motifs to create the surface that recruits NF-YA, answering how the three subunits combine to bind CCAAT.","evidence":"Recombinant reconstitution, EMSA, cross-linking, yeast two-hybrid, and mutational mapping in rat/human subunits","pmids":["7878029","8754798"],"confidence":"High","gaps":["Atomic-resolution interface not yet defined","DNA-bound conformation unresolved"]},{"year":1997,"claim":"Linked NFYB to the basal transcription machinery by showing direct NF-YB/NF-YC contacts with TBP and association with TFIID, providing a route from CCAAT recognition to initiation.","evidence":"Holo-TFIID immunopurification, sedimentation velocity, and domain-mapped in vitro interaction assays","pmids":["9153318"],"confidence":"High","gaps":["Functional consequence on initiation rate not quantified in vivo","Competition with NC2 at TBP not fully resolved"]},{"year":2002,"claim":"Provided the structural basis of NF-YB/NF-YC interaction, showing histone folds related to H2A/H2B and a regulatory alphaC helix targeted by factors such as MYC and p53.","evidence":"X-ray crystallography of the NF-YB/NF-YC subcomplex with modeling of the CCAAT complex","pmids":["12401788"],"confidence":"High","gaps":["Structure of the full DNA-bound trimer not solved here","Dynamics of regulatory protein recruitment not captured"]},{"year":2010,"claim":"Identified NFYB as a partner of Dysbindin at a specific CCAAT-containing promoter, extending its role to neuronal gene regulation (MARCKS).","evidence":"Yeast two-hybrid, co-IP, ChIP, and reporter/knockdown assays in mouse brain","pmids":["20098743"],"confidence":"Medium","gaps":["Single lab","Whether Dysbindin acts within the full NF-Y trimer not established"]},{"year":2021,"claim":"Showed NFYB output can be negatively regulated through coactivator release, with IER5 displacing p300 from NF-YB at the Cdc25B promoter.","evidence":"Reporter assays, promoter mutagenesis, and ChIP in AML progenitors and irradiated HeLa cells","pmids":["22132193","34484679"],"confidence":"Medium","gaps":["Single lab series","Direct biochemical p300/NF-YB displacement not reconstituted"]},{"year":2017,"claim":"Placed NFYB in a pro-survival/chemoresistance program by demonstrating it transactivates E2F1 (itself an upstream regulator of NFYB), feeding a CHK1 axis that suppresses drug-induced apoptosis.","evidence":"Knockdown/overexpression, transcriptomics, reporter assays, and in vitro/in vivo tumor assays in colorectal cancer","pmids":["26039627","29203250"],"confidence":"Medium","gaps":["Single lab per finding","Direct ChIP occupancy at E2F1 promoter not shown in both studies"]},{"year":2023,"claim":"Expanded the activator target repertoire of NFYB to HDAC5, MBTD1, and STK33 in distinct cancer chemoresistance settings.","evidence":"ChIP/ChIP-qPCR, luciferase reporters, knockdown/overexpression, and metabolic/proliferation assays in lymphoma and glioma cells","pmids":["36434485","37742129","34536775"],"confidence":"Medium","gaps":["Each target shown by a single lab","Whether targets require the full NF-Y trimer vs NFYB alone not dissected"]},{"year":2020,"claim":"Revealed a non-canonical organismal role for the NFYB ortholog: NFYB-1 represses lysosomal prosaposin to maintain mitochondrial cardiolipin, oxygen consumption, and stress-pathway integrity.","evidence":"RNAi screens, multi-omics, oxygen consumption, mitochondrial morphology imaging, and cardiolipin rescue in C. elegans","pmids":["32694663"],"confidence":"High","gaps":["Whether mammalian NFYB performs an equivalent mitochondrial function not shown","Direct prosaposin promoter occupancy not established"]},{"year":2025,"claim":"Positioned NFYB as a cooperative dependency with menin-MLL1, with NF-Y pioneer recruitment associated with chromatin opening after menin inhibition.","evidence":"Epigenome-focused CRISPR screen and chromatin accessibility assays with menin inhibitor in HCC cells (preprint)","pmids":["bio_10.1101_2025.04.05.647381"],"confidence":"Medium","gaps":["Preprint, single lab","Direct physical link between NF-Y and menin-MLL1 not demonstrated"]},{"year":null,"claim":"How NFYB's canonical CCAAT/initiation role mechanistically connects to its mitochondrial/cardiolipin regulatory function, and whether this is conserved in mammals, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No mammalian study links NFYB to prosaposin or cardiolipin","Genome-wide direct target map integrating both roles is absent"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,6,13,19]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[0,5,6]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[9]},{"term_id":"GO:0140223","term_label":"general transcription initiation factor activity","supporting_discovery_ids":[8]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,11,19]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,6,8,13]}],"complexes":["NF-Y / CBF (CCAAT-binding factor) heterotrimer","TFIID"],"partners":["NFYC","NFYA","TBP","DTNBP1","IER5","E2F1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P25208","full_name":"Nuclear transcription factor Y subunit beta","aliases":["CAAT box DNA-binding protein subunit B","Nuclear transcription factor Y subunit B","NF-YB"],"length_aa":207,"mass_kda":22.8,"function":"Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5'-CCAAT-3' box motif found in the promoters of its target genes. NF-Y can function as both an activator and a repressor, depending on its interacting cofactors","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/P25208/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/NFYB","classification":"Common Essential","n_dependent_lines":1007,"n_total_lines":1208,"dependency_fraction":0.8336092715231788},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CAPZB","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/NFYB","total_profiled":1310},"omim":[{"mim_id":"621274","title":"COILED-COIL DOMAIN-CONTAINING PROTEIN 152; CCDC152","url":"https://www.omim.org/entry/621274"},{"mim_id":"616674","title":"SPINDLE- AND KINETOCHORE-ASSOCIATED COMPLEX, SUBUNIT 2; SKA2","url":"https://www.omim.org/entry/616674"},{"mim_id":"615920","title":"PROLINE-RICH PROTEIN 11; PRR11","url":"https://www.omim.org/entry/615920"},{"mim_id":"615385","title":"MICRO RNA 485; MIR485","url":"https://www.omim.org/entry/615385"},{"mim_id":"607267","title":"POLYMERASE, DNA, EPSILON-3; POLE3","url":"https://www.omim.org/entry/607267"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NFYB"},"hgnc":{"alias_symbol":["CBF-A","HAP3","NF-YB"],"prev_symbol":[]},"alphafold":{"accession":"P25208","domains":[{"cath_id":"1.10.20.10","chopping":"53-146","consensus_level":"medium","plddt":95.7766,"start":53,"end":146}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P25208","model_url":"https://alphafold.ebi.ac.uk/files/AF-P25208-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P25208-F1-predicted_aligned_error_v6.png","plddt_mean":69.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NFYB","jax_strain_url":"https://www.jax.org/strain/search?query=NFYB"},"sequence":{"accession":"P25208","fasta_url":"https://rest.uniprot.org/uniprotkb/P25208.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P25208/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P25208"}},"corpus_meta":[{"pmid":"2676721","id":"PMC_2676721","title":"Identification and characterization of HAP4: a third component of the CCAAT-bound HAP2/HAP3 heteromer.","date":"1989","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/2676721","citation_count":349,"is_preprint":false},{"pmid":"7878029","id":"PMC_7878029","title":"Recombinant rat CBF-C, the third subunit of CBF/NFY, allows formation of a protein-DNA complex with CBF-A and CBF-B and with yeast HAP2 and HAP3.","date":"1995","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/7878029","citation_count":253,"is_preprint":false},{"pmid":"12401788","id":"PMC_12401788","title":"The NF-YB/NF-YC structure gives insight into DNA binding and transcription regulation by CCAAT factor NF-Y.","date":"2002","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12401788","citation_count":235,"is_preprint":false},{"pmid":"2826015","id":"PMC_2826015","title":"Yeast HAP2 and HAP3 activators both bind to the CYC1 upstream activation site, UAS2, in an interdependent manner.","date":"1987","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/2826015","citation_count":211,"is_preprint":false},{"pmid":"8223474","id":"PMC_8223474","title":"Mutations in yeast HAP2/HAP3 define a hybrid CCAAT box binding domain.","date":"1993","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/8223474","citation_count":136,"is_preprint":false},{"pmid":"8754798","id":"PMC_8754798","title":"Determination of functional domains in the C subunit of the CCAAT-binding factor (CBF) necessary for formation of a CBF-DNA complex: CBF-B interacts simultaneously with both the CBF-A and CBF-C subunits to form a heterotrimeric CBF molecule.","date":"1996","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/8754798","citation_count":130,"is_preprint":false},{"pmid":"28526714","id":"PMC_28526714","title":"CONSTANS Imparts DNA Sequence Specificity to the Histone Fold NF-YB/NF-YC Dimer.","date":"2017","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/28526714","citation_count":129,"is_preprint":false},{"pmid":"2832731","id":"PMC_2832731","title":"Mutational analysis of upstream activation sequence 2 of the CYC1 gene of Saccharomyces cerevisiae: a HAP2-HAP3-responsive site.","date":"1988","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/2832731","citation_count":119,"is_preprint":false},{"pmid":"2832951","id":"PMC_2832951","title":"Yeast HAP2 and HAP3: transcriptional activators in a heteromeric complex.","date":"1988","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/2832951","citation_count":115,"is_preprint":false},{"pmid":"2832732","id":"PMC_2832732","title":"The HAP3 regulatory locus of Saccharomyces cerevisiae encodes divergent overlapping transcripts.","date":"1988","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/2832732","citation_count":108,"is_preprint":false},{"pmid":"9153318","id":"PMC_9153318","title":"CCAAT binding NF-Y-TBP interactions: NF-YB and NF-YC require short domains adjacent to their histone fold motifs for association with TBP basic residues.","date":"1997","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/9153318","citation_count":103,"is_preprint":false},{"pmid":"11971906","id":"PMC_11971906","title":"Ternary complex formation between MADS-box transcription factors and the histone fold protein NF-YB.","date":"2002","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11971906","citation_count":87,"is_preprint":false},{"pmid":"2266139","id":"PMC_2266139","title":"Purification and molecular cloning of the \"A\" chain of a rat heteromeric CCAAT-binding protein. Sequence identity with the yeast HAP3 transcription factor.","date":"1990","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/2266139","citation_count":83,"is_preprint":false},{"pmid":"32843433","id":"PMC_32843433","title":"Structural Insight into DNA Recognition by CCT/NF-YB/YC Complexes in Plant Photoperiodic Flowering.","date":"2020","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/32843433","citation_count":71,"is_preprint":false},{"pmid":"17716999","id":"PMC_17716999","title":"The tetraplex (CGG)n destabilizing proteins hnRNP A2 and CBF-A enhance the in vivo translation of fragile X premutation mRNA.","date":"2007","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/17716999","citation_count":66,"is_preprint":false},{"pmid":"29203250","id":"PMC_29203250","title":"NFYB-induced high expression of E2F1 contributes to oxaliplatin resistance in colorectal cancer via the enhancement of CHK1 signaling.","date":"2017","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/29203250","citation_count":61,"is_preprint":false},{"pmid":"10851069","id":"PMC_10851069","title":"Exogenous cdk4 overcomes reduced cdk4 RNA and inhibition of G1 progression in hematopoietic cells expressing a dominant-negative CBF - a model for overcoming inhibition of proliferation by CBF oncoproteins.","date":"2000","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/10851069","citation_count":51,"is_preprint":false},{"pmid":"38510250","id":"PMC_38510250","title":"Unraveling the intricacies of glioblastoma progression and recurrence: insights into the role of NFYB and oxidative phosphorylation at the single-cell level.","date":"2024","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/38510250","citation_count":48,"is_preprint":false},{"pmid":"18453547","id":"PMC_18453547","title":"Duplication and functional diversification of HAP3 genes leading to the origin of the seed-developmental regulatory gene, LEAFY COTYLEDON1 (LEC1), in nonseed plant genomes.","date":"2008","source":"Molecular biology and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/18453547","citation_count":45,"is_preprint":false},{"pmid":"18480411","id":"PMC_18480411","title":"In cultured oligodendrocytes the A/B-type hnRNP CBF-A accompanies MBP mRNA bound to mRNA trafficking sequences.","date":"2008","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/18480411","citation_count":45,"is_preprint":false},{"pmid":"7845362","id":"PMC_7845362","title":"Sequence of the HAP3 transcription factor of Kluyveromyces lactis predicts the presence of a novel 4-cysteine zinc-finger motif.","date":"1994","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/7845362","citation_count":45,"is_preprint":false},{"pmid":"32694663","id":"PMC_32694663","title":"NFYB-1 regulates mitochondrial function and longevity via lysosomal prosaposin.","date":"2020","source":"Nature metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/32694663","citation_count":42,"is_preprint":false},{"pmid":"1310523","id":"PMC_1310523","title":"Positive regulation of the LPD1 gene of Saccharomyces cerevisiae by the HAP2/HAP3/HAP4 activation system.","date":"1992","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/1310523","citation_count":38,"is_preprint":false},{"pmid":"8158647","id":"PMC_8158647","title":"A mutant hook-associated protein (HAP3) facilitates torsionally induced transformations of the flagellar filament of Escherichia coli.","date":"1994","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/8158647","citation_count":36,"is_preprint":false},{"pmid":"22132193","id":"PMC_22132193","title":"Transcriptional repression of Cdc25B by IER5 inhibits the proliferation of leukemic progenitor cells through NF-YB and p300 in acute myeloid leukemia.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22132193","citation_count":34,"is_preprint":false},{"pmid":"21471000","id":"PMC_21471000","title":"In neurons, activity-dependent association of dendritically transported mRNA transcripts with the transacting factor CBF-A is mediated by A2RE/RTS elements.","date":"2011","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/21471000","citation_count":33,"is_preprint":false},{"pmid":"11000268","id":"PMC_11000268","title":"CArG binding factor A (CBF-A) is involved in transcriptional regulation of the rat Ha-ras promoter.","date":"2000","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/11000268","citation_count":32,"is_preprint":false},{"pmid":"24146628","id":"PMC_24146628","title":"The transacting factor CBF-A/Hnrnpab binds to the A2RE/RTS element of protamine 2 mRNA and contributes to its translational regulation during mouse spermatogenesis.","date":"2013","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24146628","citation_count":32,"is_preprint":false},{"pmid":"9299414","id":"PMC_9299414","title":"Telomeric and tetraplex DNA binding properties of qTBP42: a homologue of the CArG box binding protein CBF-A.","date":"1997","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/9299414","citation_count":32,"is_preprint":false},{"pmid":"27304889","id":"PMC_27304889","title":"NF-YB Regulates Spermatogonial Stem Cell Self-Renewal and Proliferation in the Planarian Schmidtea mediterranea.","date":"2016","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/27304889","citation_count":23,"is_preprint":false},{"pmid":"34726281","id":"PMC_34726281","title":"TOC1 clock protein phosphorylation controls complex formation with NF-YB/C to repress hypocotyl growth.","date":"2021","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/34726281","citation_count":21,"is_preprint":false},{"pmid":"8208248","id":"PMC_8208248","title":"MBR1 and MBR3, two related yeast genes that can suppress the growth defect of hap2, hap3 and hap4 mutants.","date":"1994","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/8208248","citation_count":21,"is_preprint":false},{"pmid":"11105902","id":"PMC_11105902","title":"CBF--a biophysical perspective.","date":"2000","source":"Seminars in cell & developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/11105902","citation_count":20,"is_preprint":false},{"pmid":"34536775","id":"PMC_34536775","title":"NFYB potentiates STK33 activation to promote cisplatin resistance in diffuse large B-cell lymphoma.","date":"2021","source":"Leukemia research","url":"https://pubmed.ncbi.nlm.nih.gov/34536775","citation_count":15,"is_preprint":false},{"pmid":"26039627","id":"PMC_26039627","title":"E2F1-Mediated Induction of NFYB Attenuates Apoptosis via Joint Regulation of a Pro-Survival Transcriptional Program.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26039627","citation_count":15,"is_preprint":false},{"pmid":"29415481","id":"PMC_29415481","title":"Genome-Wide Analysis of the NF-YB Gene Family in Gossypium hirsutum L. and Characterization of the Role of GhDNF-YB22 in Embryogenesis.","date":"2018","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/29415481","citation_count":15,"is_preprint":false},{"pmid":"31213550","id":"PMC_31213550","title":"Nuclear Factor Y (NF-Y) Modulates Encystation in Entamoeba via Stage-Specific Expression of the NF-YB and NF-YC Subunits.","date":"2019","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/31213550","citation_count":14,"is_preprint":false},{"pmid":"20098743","id":"PMC_20098743","title":"Dysbindin regulates the transcriptional level of myristoylated alanine-rich protein kinase C substrate via the interaction with NF-YB in mice brain.","date":"2010","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/20098743","citation_count":14,"is_preprint":false},{"pmid":"31185907","id":"PMC_31185907","title":"Genome-wide analysis of poplar NF-YB gene family and identified PtNF-YB1 important in regulate flowering timing in transgenic plants.","date":"2019","source":"BMC plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/31185907","citation_count":10,"is_preprint":false},{"pmid":"35805915","id":"PMC_35805915","title":"Identification and Characterization of Abiotic Stress-Responsive NF-YB Family Genes in Medicago.","date":"2022","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/35805915","citation_count":9,"is_preprint":false},{"pmid":"34072675","id":"PMC_34072675","title":"NF-YB-Mediated Active Responses of Plant Growth under Salt and Temperature Stress in Eucalyptus grandis.","date":"2021","source":"Plants (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/34072675","citation_count":9,"is_preprint":false},{"pmid":"39722010","id":"PMC_39722010","title":"Overexpression of an NF-YB gene family member, EaNF-YB2, enhances drought tolerance in sugarcane (Saccharum Spp. Hybrid).","date":"2024","source":"BMC plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/39722010","citation_count":7,"is_preprint":false},{"pmid":"7509302","id":"PMC_7509302","title":"Studies on the structure of the mouse CBF-A gene and properties of a truncated CBF-A isoform generated from an alternatively spliced RNA.","date":"1994","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/7509302","citation_count":7,"is_preprint":false},{"pmid":"17901702","id":"PMC_17901702","title":"Exclusion of NFYB as candidate gene for congenital splay leg in piglets and radiation hybrid mapping of further five homologous porcine genes from human chromosome 12 (HSA12).","date":"2007","source":"Cytogenetic and genome research","url":"https://pubmed.ncbi.nlm.nih.gov/17901702","citation_count":6,"is_preprint":false},{"pmid":"16360014","id":"PMC_16360014","title":"The kappa promoter penta-decamer binding protein CBF-A interacts specifically with nucleophosmin in the nucleus only.","date":"2005","source":"Molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/16360014","citation_count":6,"is_preprint":false},{"pmid":"37742129","id":"PMC_37742129","title":"NFYB increases chemosensitivity in glioblastoma by promoting HDAC5-mediated transcriptional inhibition of SHMT2.","date":"2023","source":"Journal of neuropathology and experimental neurology","url":"https://pubmed.ncbi.nlm.nih.gov/37742129","citation_count":5,"is_preprint":false},{"pmid":"36152055","id":"PMC_36152055","title":"Over-expression of NFYB affects stromal cells reprogramming and predicts worse survival in gastric cancer patients.","date":"2022","source":"Aging","url":"https://pubmed.ncbi.nlm.nih.gov/36152055","citation_count":5,"is_preprint":false},{"pmid":"29137403","id":"PMC_29137403","title":"Chicken CCDC152 shares an NFYB-regulated bidirectional promoter with a growth hormone receptor antisense transcript and inhibits cells proliferation and migration.","date":"2017","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/29137403","citation_count":5,"is_preprint":false},{"pmid":"26037219","id":"PMC_26037219","title":"Identification and characterization of NF-YB family genes in tung tree.","date":"2015","source":"Molecular genetics and genomics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/26037219","citation_count":5,"is_preprint":false},{"pmid":"34484679","id":"PMC_34484679","title":"Cdc25B is transcriptionally inhibited by IER5 through the NF-YB transcription factor in irradiation-treated HeLa cells.","date":"2021","source":"Toxicology research","url":"https://pubmed.ncbi.nlm.nih.gov/34484679","citation_count":5,"is_preprint":false},{"pmid":"36434485","id":"PMC_36434485","title":"Long Non-coding RNA H19 Recruits NFYB to Activate MBTD1 and Regulate Doxorubicin Resistance in Lymphoma Cells.","date":"2022","source":"Molecular biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/36434485","citation_count":4,"is_preprint":false},{"pmid":"38795876","id":"PMC_38795876","title":"Coptisine-mediated downregulation of E2F7 induces G2/M phase arrest in hepatocellular carcinoma cells through inhibition of E2F4/NFYA/NFYB transcription factors.","date":"2024","source":"Chemico-biological interactions","url":"https://pubmed.ncbi.nlm.nih.gov/38795876","citation_count":4,"is_preprint":false},{"pmid":"8760361","id":"PMC_8760361","title":"Identification of the transcription factors NF-YA and NF-YB as factors A and B that bound to the promoter of the major histocompatibility complex class II gene I-A beta.","date":"1996","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/8760361","citation_count":4,"is_preprint":false},{"pmid":"37841620","id":"PMC_37841620","title":"Transcription factors NF-YB involved in embryogenesis and hormones responses in Dimocarpus Longan Lour.","date":"2023","source":"Frontiers in plant science","url":"https://pubmed.ncbi.nlm.nih.gov/37841620","citation_count":3,"is_preprint":false},{"pmid":"32150428","id":"PMC_32150428","title":"Attentional set shifting in HAP3, LAP3, and cHAP mice is unaffected by either genetic differences in alcohol preference or an alcohol drinking history.","date":"2020","source":"Experimental and clinical psychopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/32150428","citation_count":2,"is_preprint":false},{"pmid":"14697263","id":"PMC_14697263","title":"Temperature may influence and regulate NF-YB expression in toad oocyte.","date":"2004","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/14697263","citation_count":2,"is_preprint":false},{"pmid":"37240255","id":"PMC_37240255","title":"Comprehensive Analysis of the NF-YB Gene Family and Expression under Abiotic Stress and Hormone Treatment in Larix kaempferi.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37240255","citation_count":1,"is_preprint":false},{"pmid":"40762860","id":"PMC_40762860","title":"Enhancing HAP3 mediated xylose metabolism and acetic acid metabolism promotes lipid production from lignocellulosic hydrolysate fermented by Candida glycerinogenes.","date":"2025","source":"Biotechnology letters","url":"https://pubmed.ncbi.nlm.nih.gov/40762860","citation_count":1,"is_preprint":false},{"pmid":"42160015","id":"PMC_42160015","title":"NFYB Integrates Hormonal Signals into Tissue Allometry by Promoting Protein Biosynthesis.","date":"2026","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/42160015","citation_count":0,"is_preprint":false},{"pmid":"40505546","id":"PMC_40505546","title":"NF-YB-driven expression of long non-coding RNA linc01811 inhibiting glioma tumorigenesis by regulating miR-4635/NF-YB axis: A positive feedback loop.","date":"2025","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/40505546","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.04.05.647381","title":"Menin-MLL1 complex cooperates with NF-Y to promote HCC survival","date":"2025-04-08","source":"bioRxiv","url":"https://doi.org/10.1101/2025.04.05.647381","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":31007,"output_tokens":5007,"usd":0.084063,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":13156,"output_tokens":3825,"usd":0.080702,"stage2_stop_reason":"end_turn"},"total_usd":0.164765,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1987,\n      \"finding\": \"HAP3 (yeast ortholog of NFYB) and HAP2 bind interdependently to the CCAAT-containing UAS2 of CYC1; neither protein binds DNA alone, and binding of either is abolished when the complementary HAP gene is mutated, demonstrating that they form a heteromeric DNA-binding complex.\",\n      \"method\": \"Nondenaturing PAGE gel shift with beta-galactosidase and LexA fusion proteins; methylation interference footprinting; in vitro DNA binding with yeast extracts\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with tagged fusions, footprinting, replicated across multiple labs\",\n      \"pmids\": [\"2826015\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1988,\n      \"finding\": \"HAP2 and HAP3 associate with each other in the absence of DNA to form a multisubunit activation complex, as shown by co-purification through four chromatographic steps.\",\n      \"method\": \"Co-purification of LexA-HAP2 and HAP3-beta-galactosidase fusion proteins through four chromatographic steps; DNA binding activity co-purified with the complex\",\n      \"journal\": \"Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — biochemical co-purification with tagged fusions demonstrating pre-formed complex independent of DNA\",\n      \"pmids\": [\"2832951\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1988,\n      \"finding\": \"HAP3 encodes a 144-amino acid protein essential for UAS2 activity and growth on non-fermentable carbon sources; the 86-amino acid ORF in the antisense transcript is not involved in UAS2 activity.\",\n      \"method\": \"Chromosomal disruption, site-directed mutagenesis, in vivo complementation, reporter assays\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic loss-of-function with defined phenotypic readout, mutagenesis, multiple orthogonal experiments\",\n      \"pmids\": [\"2832732\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1989,\n      \"finding\": \"HAP4 is a third subunit of the HAP2/HAP3 DNA-binding complex at UAS2; HAP4 is required for detectable HAP2/HAP3 binding in vitro and provides the principal transcriptional activation domain to the complex.\",\n      \"method\": \"Genetic analysis; in vitro DNA binding; deletion analysis of HAP4; GAL4 activation domain swap\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro binding assay plus mutagenesis plus genetic epistasis, replicated\",\n      \"pmids\": [\"2676721\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1990,\n      \"finding\": \"Mammalian CBF-A (NF-YB) is the 'A' chain of the CCAAT-binding factor (CBF) heteromer, and its deduced amino acid sequence shares remarkable identity (~90 residues) with yeast HAP3, establishing evolutionary conservation of the NFYB subunit.\",\n      \"method\": \"Protein purification by DNA affinity chromatography; tryptic peptide sequencing; cDNA cloning and in vitro transcription/translation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — biochemical purification to homogeneity, sequence identity confirmed, in vitro translation product confirmed\",\n      \"pmids\": [\"2266139\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1993,\n      \"finding\": \"Short regions of HAP3 (NFYB ortholog) form a hybrid DNA-binding domain with HAP2; a seven-amino-acid region in HAP3 is critical for DNA binding, and HAP3 mutations suppress multiple HAP2 DNA-binding domain mutations, indicating direct structural cooperation.\",\n      \"method\": \"Genetic mutational analysis; in vitro DNA binding; intragenic suppressor analysis\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — mutagenesis with suppressor genetics, multiple alleles tested\",\n      \"pmids\": [\"8223474\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"Rat CBF-C (NF-YC) is required together with CBF-A (NF-YB) and CBF-B (NF-YA) to form a CBF-DNA complex; CBF-A and CBF-C interact directly with each other, and CBF-B does not interact with either subunit individually but associates with the CBF-A/CBF-C heterodimer.\",\n      \"method\": \"Recombinant protein expression; in vitro EMSA/DNA binding reconstitution; protein-protein interaction assays; cross-complementation with yeast HAP2/HAP3\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — full reconstitution of heterotrimeric complex with recombinant proteins, multiple orthogonal assays\",\n      \"pmids\": [\"7878029\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1996,\n      \"finding\": \"CBF-A (NF-YB) and CBF-C (NF-YC) interact through their histone fold motifs to form a heterodimer; this heterodimer generates a tridentate interaction surface that binds CBF-B (NF-YA) to form the heterotrimeric CBF; the evolutionarily conserved histone-fold segment of CBF-C is necessary for DNA complex formation.\",\n      \"method\": \"Cross-linking; immunoprecipitation; mutational analysis; yeast two-hybrid; in vitro DNA binding assays\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — reciprocal interaction mapping with mutagenesis, multiple orthogonal methods, two-hybrid plus biochemical validation\",\n      \"pmids\": [\"8754798\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"NF-YB and NF-YC each interact directly with TBP in solution; short domains adjacent to their histone fold motifs are necessary for TBP binding; a fraction of NF-YB associates with TFIID (in the absence of NF-YA); TBP mutants in the HS2 helix defective in NC2 binding are also unable to bind NF-YB and NF-YC.\",\n      \"method\": \"Immunopurification of holo-TFIID; sedimentation velocity centrifugation; in vitro protein-protein interaction assays with truncation/domain mutants\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct interaction assays with domain mapping, multiple orthogonal biochemical methods in single study\",\n      \"pmids\": [\"9153318\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"The crystal structure of the NF-YB/NF-YC subcomplex shows that their core domains interact through histone fold motifs closely related to H2A/H2B and NC2alpha/NC2beta; the alphaC helix of NF-YC is important both for NF-Y trimerization and as a target for regulatory proteins such as MYC and p53.\",\n      \"method\": \"X-ray crystallography; structural modeling of NF-YC/NF-YB with DNA and full NF-Y/CCAAT complex\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure determination with functional modeling, defines molecular basis of subunit interaction\",\n      \"pmids\": [\"12401788\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"MADS-box protein OsMADS18 forms a ternary complex with rice NF-YB (OsNF-YB1) via the MADS and I regions; mouse NF-YB also associates with OsMADS18 as an NF-YB/NF-YC dimer; OsNF-YB1 can heterodimerize with NF-YC but cannot trimerize with NF-YA, precluding CCAAT binding; mutation of Asp99 in the HFM alpha2-helix of OsNF-YB1 to the conserved Ser recovers NF-YA interaction but not DNA binding.\",\n      \"method\": \"Yeast two-hybrid screening; in vitro and in vivo protein-protein interaction assays; site-directed mutagenesis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal two-hybrid plus in vitro/in vivo assays, single lab, plant ortholog with mammalian NF-YB confirmation\",\n      \"pmids\": [\"11971906\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Dysbindin physically interacts with NF-YB in mouse brain; this complex binds the CCAAT motif at the MARCKS promoter and regulates MARCKS transcription; knockdown of either Dysbindin or NF-YB increases MARCKS expression.\",\n      \"method\": \"Yeast two-hybrid screening; co-immunoprecipitation; chromatin immunoprecipitation; reporter assay; DNA chip gene expression profiling\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — co-IP plus ChIP plus reporter assay, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"20098743\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"IER5 reduces Cdc25B mRNA expression through direct binding to the Cdc25B promoter and mediates transcriptional repression via release of NF-YB and p300 co-activator, inhibiting AML progenitor cell proliferation.\",\n      \"method\": \"Reporter assays; chromatin immunoprecipitation; gene knockdown/overexpression; colony formation assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — ChIP plus reporter assay plus functional rescue, single lab\",\n      \"pmids\": [\"22132193\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"NFYB is a direct transcriptional target of E2F1; NFYB knockdown enhances E2F1-induced apoptosis, indicating that the NFYB/E2F1 joint transcriptional program has a pro-survival function.\",\n      \"method\": \"Genome-wide expression analysis; NFYB knockdown; apoptosis assays; E2F1 overexpression\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — genome-wide analysis with functional knockdown, single lab, defined phenotypic readout\",\n      \"pmids\": [\"26039627\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"NFYB transactivates the E2F1 gene in oxaliplatin-resistant colorectal cancer cells; the NFYB-E2F1-CHK1 axis suppresses oxaliplatin-induced apoptosis and maintains tumorigenicity in vitro and in vivo.\",\n      \"method\": \"Gene knockdown/overexpression; transcriptome profiling; in vitro and in vivo phenotype experiments; reporter assays\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — functional knockdown/OE with defined phenotype plus transcriptomics, single lab\",\n      \"pmids\": [\"29203250\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"C. elegans NFYB-1 is a crucial regulator of mitochondrial function; its loss leads to perturbed mitochondrial gene expression, reduced oxygen consumption, mitochondrial fragmentation, disrupted mitochondrial stress pathways, and decreased cardiolipin levels. NFYB-1 acts as a repressor of lysosomal prosaposin; limiting prosaposin restores cardiolipin production and mitochondrial function in nfyb-1 mutants.\",\n      \"method\": \"RNAi screens; multi-omics analysis (transcriptomics, metabolomics); oxygen consumption assays; microscopy of mitochondrial morphology; cardiolipin supplementation rescue\",\n      \"journal\": \"Nature metabolism\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multi-omics with multiple orthogonal functional assays and genetic rescue experiments, replicated in C. elegans model\",\n      \"pmids\": [\"32694663\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"IER5 represses Cdc25B transcription in irradiated HeLa cells via the NF-YB binding site on the Cdc25B promoter; IER5 binds the Cdc25B promoter and induces release of the coactivator p300 through interaction with NF-YB.\",\n      \"method\": \"Dual-luciferase reporter assays; site-directed mutagenesis of promoter elements; chromatin immunoprecipitation (ChIP); irradiation model\",\n      \"journal\": \"Toxicology research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — ChIP plus reporter assay plus mutagenesis, single lab, confirms NF-YB as the relevant promoter element\",\n      \"pmids\": [\"34484679\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"NFYB can bind to the STK33 promoter and promote STK33 expression, thereby activating the Hedgehog signaling pathway and promoting cisplatin resistance in DLBCL cells.\",\n      \"method\": \"Bioinformatics prediction; luciferase reporter assay; gene knockdown; cell sensitivity assays\",\n      \"journal\": \"Leukemia research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, reporter assay without direct ChIP confirmation, limited mechanistic follow-up\",\n      \"pmids\": [\"34536775\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"H19 lncRNA recruits NFYB to the MBTD1 promoter to activate MBTD1 transcription, promoting doxorubicin resistance in lymphoma cells; H19 increases MBTD1 expression in a NFYB-dependent manner without altering NFYB levels.\",\n      \"method\": \"Luciferase reporter assay; ChIP-qPCR; gene knockdown and overexpression; in vitro and in vivo growth assays\",\n      \"journal\": \"Molecular biotechnology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — ChIP-qPCR plus reporter plus functional rescue, single lab\",\n      \"pmids\": [\"36434485\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"NFYB activates HDAC5 transcription by binding to the HDAC5 promoter; HDAC5 in turn inhibits SHMT2 expression, reducing glycolysis and increasing TMZ sensitivity in GBM cells.\",\n      \"method\": \"Chromatin immunoprecipitation; dual-luciferase reporter assay; gene overexpression/knockdown; glucose uptake and lactate production assays; proliferation and apoptosis assays\",\n      \"journal\": \"Journal of neuropathology and experimental neurology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — ChIP plus reporter plus functional rescue assays, single lab, multiple cellular readouts\",\n      \"pmids\": [\"37742129\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Coptisine downregulates E2F7 in HCC by inhibiting E2F4/NF-YA/NF-YB transcription factor activity at the E2F7 promoter, as confirmed by promoter fragmentation experiments and ChIP.\",\n      \"method\": \"Promoter fragmentation experiments; chromatin immunoprecipitation; RNA-Seq; in vitro and in vivo HCC growth assays\",\n      \"journal\": \"Chemico-biological interactions\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — ChIP plus promoter analysis, single lab, demonstrates NF-YB participation in E2F7 promoter complex\",\n      \"pmids\": [\"38795876\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"NFYB knockout combined with menin-MLL1 inhibition causes significantly increased HCC cell death; menin inhibition increases chromatin accessibility at sites not bound by menin-MLL1 that are associated with NF-Y pioneer factor recruitment, placing NFYB in a cooperative oncogenic gene regulation pathway with menin-MLL1.\",\n      \"method\": \"CRISPR/Cas9 screen; epigenome-focused CRISPR library screen in 2D and 3D HCC cell lines; chromatin accessibility assays; menin inhibitor (SNDX-5613) treatment\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — CRISPR functional screen with chromatin assays, preprint, single lab\",\n      \"pmids\": [\"bio_10.1101_2025.04.05.647381\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"NFYB (NF-YB/CBF-A/HAP3) is the histone fold domain-containing subunit of the evolutionarily conserved heterotrimeric NF-Y transcription factor complex: it dimerizes with NF-YC via histone fold motifs, and this dimer recruits NF-YA to form the full trimer that binds CCAAT promoter elements; it also contacts TBP/TFIID to facilitate transcription initiation, acts as a transcriptional activator of target genes including E2F1, HDAC5, STK33, and MBTD1, and in C. elegans represses lysosomal prosaposin to maintain mitochondrial cardiolipin levels and organismal longevity.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NFYB (NF-YB/CBF-A/HAP3) is the histone-fold subunit of the evolutionarily conserved heterotrimeric NF-Y/CCAAT-binding transcription factor, a complex first defined in yeast where HAP3 and HAP2 bind interdependently to the CCAAT element of CYC1 and pre-assemble into a multisubunit complex independent of DNA [#0, #1]. The mammalian subunit CBF-A is the direct ortholog of HAP3, with a deeply conserved core [#4]. NFYB heterodimerizes with NF-YC through their histone-fold motifs, generating a tridentate surface that recruits NF-YA to form the trimer competent for CCAAT-element binding [#6, #7]; the crystal structure of the NF-YB/NF-YC subcomplex shows these histone folds are closely related to H2A/H2B and NC2 [#9]. NFYB additionally contacts the general transcription machinery, interacting directly with TBP and associating with TFIID to couple CCAAT recognition to transcription initiation [#8]. Through this promoter-binding activity NFYB acts as a transcriptional activator across diverse target genes, transactivating E2F1 and contributing to a pro-survival, chemoresistance-promoting program in cancer cells [#13, #14], and binding the promoters of HDAC5, MBTD1, and STK33 in additional resistance contexts [#18, #19]. Its recruitment and output are modulated by partner proteins including Dysbindin at the MARCKS promoter [#11] and IER5, which represses Cdc25B by triggering release of the p300 coactivator from NF-YB [#12, #16]. Beyond its transcriptional role, the C. elegans ortholog NFYB-1 maintains mitochondrial function and cardiolipin levels by repressing lysosomal prosaposin [#15].\"\n,\n  \"teleology\": [\n    {\n      \"year\": 1988,\n      \"claim\": \"Established that the NFYB ortholog HAP3 is an essential gene product that cannot bind CCAAT DNA alone but must partner with HAP2, defining NF-Y as an obligate heteromeric DNA-binding factor.\",\n      \"evidence\": \"Gel-shift, footprinting, and chromosomal disruption/complementation with tagged HAP2/HAP3 fusions in yeast\",\n      \"pmids\": [\"2826015\", \"2832732\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve which residues mediate the protein-protein interaction\", \"Mammalian subunit composition not yet defined\"]\n    },\n    {\n      \"year\": 1988,\n      \"claim\": \"Showed that HAP2 and HAP3 pre-assemble into a stable complex in the absence of DNA, indicating subunit dimerization precedes DNA engagement.\",\n      \"evidence\": \"Co-purification of LexA-HAP2 and HAP3-beta-galactosidase fusions through four chromatographic steps\",\n      \"pmids\": [\"2832951\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not identify additional subunits required for full activation\", \"Structural basis of association unknown\"]\n    },\n    {\n      \"year\": 1990,\n      \"claim\": \"Connected the yeast and mammalian systems by demonstrating that mammalian CBF-A is the histone-fold-bearing ortholog of HAP3, establishing evolutionary conservation of the NFYB subunit.\",\n      \"evidence\": \"DNA affinity purification, tryptic peptide sequencing, and cDNA cloning of mammalian CBF\",\n      \"pmids\": [\"2266139\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full mammalian trimer composition not yet reconstituted\", \"Conserved residues mediating dimerization not mapped\"]\n    },\n    {\n      \"year\": 1996,\n      \"claim\": \"Defined the assembly logic of the mammalian trimer: NF-YB and NF-YC dimerize via histone-fold motifs to create the surface that recruits NF-YA, answering how the three subunits combine to bind CCAAT.\",\n      \"evidence\": \"Recombinant reconstitution, EMSA, cross-linking, yeast two-hybrid, and mutational mapping in rat/human subunits\",\n      \"pmids\": [\"7878029\", \"8754798\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Atomic-resolution interface not yet defined\", \"DNA-bound conformation unresolved\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Linked NFYB to the basal transcription machinery by showing direct NF-YB/NF-YC contacts with TBP and association with TFIID, providing a route from CCAAT recognition to initiation.\",\n      \"evidence\": \"Holo-TFIID immunopurification, sedimentation velocity, and domain-mapped in vitro interaction assays\",\n      \"pmids\": [\"9153318\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence on initiation rate not quantified in vivo\", \"Competition with NC2 at TBP not fully resolved\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Provided the structural basis of NF-YB/NF-YC interaction, showing histone folds related to H2A/H2B and a regulatory alphaC helix targeted by factors such as MYC and p53.\",\n      \"evidence\": \"X-ray crystallography of the NF-YB/NF-YC subcomplex with modeling of the CCAAT complex\",\n      \"pmids\": [\"12401788\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structure of the full DNA-bound trimer not solved here\", \"Dynamics of regulatory protein recruitment not captured\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Identified NFYB as a partner of Dysbindin at a specific CCAAT-containing promoter, extending its role to neuronal gene regulation (MARCKS).\",\n      \"evidence\": \"Yeast two-hybrid, co-IP, ChIP, and reporter/knockdown assays in mouse brain\",\n      \"pmids\": [\"20098743\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Whether Dysbindin acts within the full NF-Y trimer not established\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Showed NFYB output can be negatively regulated through coactivator release, with IER5 displacing p300 from NF-YB at the Cdc25B promoter.\",\n      \"evidence\": \"Reporter assays, promoter mutagenesis, and ChIP in AML progenitors and irradiated HeLa cells\",\n      \"pmids\": [\"22132193\", \"34484679\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab series\", \"Direct biochemical p300/NF-YB displacement not reconstituted\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Placed NFYB in a pro-survival/chemoresistance program by demonstrating it transactivates E2F1 (itself an upstream regulator of NFYB), feeding a CHK1 axis that suppresses drug-induced apoptosis.\",\n      \"evidence\": \"Knockdown/overexpression, transcriptomics, reporter assays, and in vitro/in vivo tumor assays in colorectal cancer\",\n      \"pmids\": [\"26039627\", \"29203250\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab per finding\", \"Direct ChIP occupancy at E2F1 promoter not shown in both studies\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Expanded the activator target repertoire of NFYB to HDAC5, MBTD1, and STK33 in distinct cancer chemoresistance settings.\",\n      \"evidence\": \"ChIP/ChIP-qPCR, luciferase reporters, knockdown/overexpression, and metabolic/proliferation assays in lymphoma and glioma cells\",\n      \"pmids\": [\"36434485\", \"37742129\", \"34536775\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Each target shown by a single lab\", \"Whether targets require the full NF-Y trimer vs NFYB alone not dissected\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Revealed a non-canonical organismal role for the NFYB ortholog: NFYB-1 represses lysosomal prosaposin to maintain mitochondrial cardiolipin, oxygen consumption, and stress-pathway integrity.\",\n      \"evidence\": \"RNAi screens, multi-omics, oxygen consumption, mitochondrial morphology imaging, and cardiolipin rescue in C. elegans\",\n      \"pmids\": [\"32694663\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether mammalian NFYB performs an equivalent mitochondrial function not shown\", \"Direct prosaposin promoter occupancy not established\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Positioned NFYB as a cooperative dependency with menin-MLL1, with NF-Y pioneer recruitment associated with chromatin opening after menin inhibition.\",\n      \"evidence\": \"Epigenome-focused CRISPR screen and chromatin accessibility assays with menin inhibitor in HCC cells (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.04.05.647381\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, single lab\", \"Direct physical link between NF-Y and menin-MLL1 not demonstrated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How NFYB's canonical CCAAT/initiation role mechanistically connects to its mitochondrial/cardiolipin regulatory function, and whether this is conserved in mammals, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No mammalian study links NFYB to prosaposin or cardiolipin\", \"Genome-wide direct target map integrating both roles is absent\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 6, 13, 19]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [0, 5, 6]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [9]},\n      {\"term_id\": \"GO:0140223\", \"supporting_discovery_ids\": [8]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 11, 19]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 6, 8, 13]}\n    ],\n    \"complexes\": [\"NF-Y / CBF (CCAAT-binding factor) heterotrimer\", \"TFIID\"],\n    \"partners\": [\"NFYC\", \"NFYA\", \"TBP\", \"DTNBP1\", \"IER5\", \"E2F1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}