Affinage

NFYA

Nuclear transcription factor Y subunit alpha · UniProt P23511

Length
347 aa
Mass
36.9 kDa
Annotated
2026-06-10
87 papers in source corpus 40 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/8 claims corpus-supported (75%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NFYA (NF-YA/CBF-B) is the sequence-specific, regulatory subunit of the heterotrimeric NF-Y/CBF transcription factor that binds CCAAT-box promoters to control gene programs spanning the cell cycle, stem cell self-renewal, metabolism, DNA repair, and development (PMID:7878029, PMID:8754798, PMID:38199563). Its C-terminal HAP2-homology domain carries two functionally separable subdomains—a 21-amino-acid stretch that mediates subunit association and a distinct segment that contacts DNA—and is necessary and sufficient for assembly with the NF-YB/NF-YC histone-fold dimer and for DNA binding; NF-YA does not bind either partner alone but joins the preformed NF-YB–NF-YC dimer to complete the trimer (PMID:7878029, PMID:8051128, PMID:8754798). NF-YA itself contributes no activation domain, transcriptional output being supplied by NF-YB and NF-YC (PMID:8662945). DNA binding and protein dosage are tightly gated post-translationally: CDK2-phosphorylated Ser320 contacts the DNA backbone and is required for full CCAAT binding and transactivation (PMID:30589568), while competition between p300-mediated acetylation and ubiquitylation of C-terminal lysines sets NF-YA stability, with degradation-resistant protein driving sustained mitotic cyclin expression and proliferation (PMID:18815279). Stability is further controlled by an MDM2 ubiquitylation axis antagonized by circPTK2 (PMID:41204684). Functionally, NF-YA acts as a pioneer factor that establishes open chromatin at CCAAT promoters of meiotic genes and of cell-cycle genes in neural progenitors, with conditional deletion blocking meiotic entry and depleting neural progenitors (PMID:41857150, PMID:38199563); it likewise drives cardiomyocyte proliferation and mitochondrial metabolism in cooperation with SP2 (PMID:37972593). Two alternatively spliced isoforms exert opposing roles, the short isoform favoring proliferation/stemness and the long isoform favoring differentiation/migration (PMID:26921500, PMID:34782004). Through direct CCAAT binding NF-YA activates a broad target set including EZH2, SOX2, CDK4/CCND1, PLK1, GADD45, OGG1, GLUL, PCK1, and FOXM1, and partners with co-regulators including p21, ZHX2, GATA/CREB, and Bcl6 to tune output (PMID:24407240, PMID:25473899, PMID:17226765, PMID:23360797, PMID:31365524, PMID:32905496).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    Established how the NF-Y trimer assembles: NF-YA's contribution and the requirement for a preformed partner dimer were unknown; reconstitution showed NF-YA binds only the NF-YB–NF-YC dimer, not either subunit alone, defining the assembly hierarchy.

    Evidence Recombinant reconstitution, EMSA, co-IP, cross-linking, yeast two-hybrid and mutagenesis across two studies

    PMID:7878029 PMID:8754798

    Open questions at the time
    • No high-resolution structure of the assembled trimer on DNA in these studies
    • Stoichiometry of cooperative DNA recognition not fully resolved
  2. 1994 High

    Mapped the functional architecture of NF-YA: it was unclear which region mediates partner binding versus DNA contact; mutagenesis localized both to the C-terminal HAP2 domain in two separable subdomains and showed DNA-binding mutants act as dominant repressors.

    Evidence Protein affinity columns with substitution mutants, dominant-negative and reporter assays

    PMID:8051128

    Open questions at the time
    • Did not define how the two subdomains are spatially coordinated on DNA
    • Activation contribution of each subunit not addressed here
  3. 1996 High

    Resolved which subunit drives transactivation: NF-YA's role in activation was untested; in vitro transcription showed activation domains reside in NF-YB and NF-YC, not NF-YA, casting NF-YA as the DNA-targeting/regulatory subunit.

    Evidence Reconstituted in vitro transcription with subunit deletion mutants in depleted extracts

    PMID:8662945

    Open questions at the time
    • In vitro assay may not capture context-dependent coactivator recruitment in vivo
  4. 2003 Medium

    Connected NF-YA to genotoxic-stress gene induction: it was unknown whether NF-YA participates in DNA-damage transcriptional responses; NF-YA was shown to be induced by damage and to bind CCAAT boxes in the GADD45 and OGG1 promoters to drive their induction.

    Evidence EMSA/supershift, promoter mutagenesis, reporter assays, Western blot

    PMID:11420680 PMID:14688259

    Open questions at the time
    • Upstream signal coupling NF-YA induction to damage not defined
    • Single-lab promoter studies without genetic loss-of-function
  5. 2008 High

    Defined post-translational control of NF-YA dosage: how NF-YA abundance is set was unclear; C-terminal lysines were shown to be ubiquitylation targets in competition with p300 acetylation, and degradation-resistant NF-YA sustained mitotic cyclins and proliferation.

    Evidence Lysine mutagenesis, cycloheximide chase, in vitro p300 acetylation, proliferation assays

    PMID:18815279

    Open questions at the time
    • Responsible E3 ligase not identified in this study
    • In vivo physiological trigger for the acetylation/ubiquitylation switch unknown
  6. 2018 High

    Established phospho-control of DNA binding: the functional consequence of NF-YA phosphorylation was unresolved; Ser320 was shown to contact the DNA backbone, be the major phospho-isoform, and to be required for CCAAT binding and transactivation.

    Evidence Phosphomimetic EMSA, transactivation assays, phosphoproteomics, structural modeling

    PMID:30589568

    Open questions at the time
    • CDK2 as the in vivo kinase inferred but not genetically validated here
    • Cell-cycle dynamics of Ser320 occupancy at endogenous promoters not mapped
  7. 2014 High

    Linked NF-YA to cell-cycle checkpoint control via p21: how DNA damage restrains NF-Y target promoters was unclear; p21 was shown to bind NF-YA directly and displace CDK2 at the PLK1 promoter, repressing PLK1 and enabling p53-mediated protection from mitotic death.

    Evidence Direct binding assay, reciprocal co-IP, ChIP, reporter assays, siRNA

    PMID:24407240

    Open questions at the time
    • Generality of p21–NF-YA displacement at other CCAAT promoters not established
  8. 2015 Medium

    Identified a repressive co-regulator of NF-Y: it was unknown how NF-Y-driven MDR1 transcription is dampened; ZHX2 was shown to bind NF-YA and reduce NF-Y occupancy at the MDR1 promoter.

    Evidence Co-IP, ChIP, reporter mutagenesis, siRNA

    PMID:25473899

    Open questions at the time
    • Structural basis of ZHX2–NF-YA interaction not defined
    • Single-lab finding
  9. 2012 Medium

    Connected NF-YA to stem cell self-renewal and isoform identity: the role of NF-YA in pluripotency was unclear; the short isoform was found enriched in ESCs and required for stem cell gene expression and NANOG genomic association.

    Evidence Dominant-negative overexpression, protein transduction, ChIP-seq correlation, differentiation assays

    PMID:16081537 PMID:20616221 PMID:22969033

    Open questions at the time
    • Direct mechanistic basis for NF-Y–NANOG co-binding not resolved
    • Protein-transduction approaches not endogenous loss-of-function
  10. 2016 Medium

    Defined isoform-specific developmental functions: whether the two NF-YA splice forms differ functionally was untested; isoform overexpression showed the short form promotes proliferation while the long form drives differentiation through distinct CCAAT targets.

    Evidence Isoform-specific overexpression, expression profiling, CCAAT bioinformatics, binding assays in myoblasts; extended in prostate cancer

    PMID:26921500 PMID:34782004

    Open questions at the time
    • Mechanism by which isoforms select divergent targets not defined
    • Endogenous isoform-switch regulators unknown
  11. 2020 Medium

    Mapped direct oncogenic transcriptional targets: which CCAAT genes NF-YA drives in cancer was unclear; ChIP/EMSA confirmed direct activation of EZH2, SOX2, and CDK4/CCND1, linking NF-YA to chromatin repression, stemness, and G1/S progression.

    Evidence ChIP, EMSA, reporter mutagenesis, siRNA, cell-cycle analysis across multiple cancer models

    PMID:23360797 PMID:31365524 PMID:32905496 PMID:32954681

    Open questions at the time
    • Context-determinants of target selection across tumor types not defined
    • Each target characterized in single tumor contexts
  12. 2022 Medium

    Linked NF-YA isoforms to metabolic reprogramming: it was unclear how NF-YA controls tumor metabolism; isoform-specific studies showed the long form activates lipogenic ACACA/FASN while the short form activates gluconeogenic PCK1 driving distinct metabolic fates.

    Evidence Isoform-specific gain/loss of function, RT-PCR/Western, ROS and in vivo tumor assays

    PMID:31706909 PMID:36092708 PMID:37268670

    Open questions at the time
    • Direct promoter occupancy for some metabolic targets not shown
    • Physiological metabolic role outside tumors uncertain
  13. 2023 High

    Established NF-YA as a pioneer factor in development: whether NF-YA sets chromatin accessibility was unknown; conditional knockouts in cardiomyocytes and neural progenitors caused proliferation/metabolism defects and lethality, with ChIP-seq/ATAC-seq showing preferential cell-cycle promoter binding and loss of accessibility.

    Evidence Conditional KO mice, single-cell/spatial transcriptomics, ChIP-seq, SP2 co-factor interaction

    PMID:37972593 PMID:38199563

    Open questions at the time
    • Molecular basis of pioneer activity (nucleosome engagement) not directly demonstrated
    • Cofactor requirements for accessibility establishment incompletely mapped
  14. 2024 Medium

    Defined a metabolism-to-stability signaling axis: how energy state controls NF-YA was unclear; a PKM1-AMPK axis was shown to phosphorylate and destabilize NFYa, coupling ATP levels to cardiomyocyte cell-cycle control.

    Evidence Pkm1 point-mutation mouse, AMPK/NFYa phospho-Western, proliferation and cardiac phenotyping

    PMID:41536305

    Open questions at the time
    • AMPK phospho-sites on NFYa not mapped
    • Direct kinase-substrate reconstitution not shown
  15. 2025 Medium

    Revealed MDM2-controlled stability and a senescence target: how NFYA escapes degradation in cancer was unclear; circPTK2 was shown to sequester MDM2, stabilizing NFYA, which binds the FOXM1 promoter to suppress senescence.

    Evidence Co-IP, ChIP, reporter assays, siRNA, RNA-seq

    PMID:41204684

    Open questions at the time
    • MDM2 ubiquitylation sites on NFYA not defined
    • Single-lab finding
  16. 2026 High

    Demonstrated stage-specific pioneer roles in germline and early embryo: whether NFYA gates meiotic entry and embryonic genome activation was unknown; germline and oocyte/zygote knockouts blocked meiotic entry, primordial follicle activation, and ZGA with loss of chromatin accessibility at target promoters.

    Evidence Conditional and acute knockouts, single-cell ATAC-seq, RNA-seq, spatial transcriptomics

    PMID:41857150 PMID:41959188

    Open questions at the time
    • Determinants of promoter-versus-enhancer binding switch not resolved
    • Oocyte/zygote findings remain in preprint form

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NF-YA's pioneer activity, isoform choice, and the array of post-translational inputs (CDK2/Ser320, AMPK, p300 acetylation, MDM2/circPTK2 ubiquitylation) are integrated at the chromatin level to select context-specific target programs remains unresolved.
  • No unified model coupling PTM state to genome-wide binding
  • Mechanism of nucleosome engagement underlying pioneer function undefined
  • Regulators governing isoform splice choice in vivo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 6 GO:0140110 transcription regulator activity 5
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 3
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-1266738 Developmental Biology 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-4839726 Chromatin organization 2
Partners
CDK2CDKN1AEP300MDM2NFYBNFYCSP2ZHX2
Complex memberships
NF-Y/CBF heterotrimer (NF-YA/NF-YB/NF-YC)

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 CBF-C (NF-YC) is required together with CBF-A (NF-YB) and CBF-B (NF-YA) to form a CBF/NF-Y–DNA complex. CBF-A and CBF-C interact with each other to form a heterodimer, and CBF-B does not interact with CBF-A or CBF-C individually but associates with the CBF-A–CBF-C complex. All three subunits are present in the protein–DNA complex. Recombinant protein reconstitution, EMSA/DNA-binding assay, co-immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America High 7878029
1994 The C-terminal HAP2-homology domain of NF-YA (CBF-B) is necessary and sufficient for interaction with NF-YB and for DNA binding. This domain contains two functionally separable subdomains: a 21-amino-acid stretch mediating subunit association and a distinct short segment mediating DNA interaction. DNA-binding mutants of NF-YA act as dominant repressors of NF-Y–DNA complex formation and NF-Y-dependent transcription. Protein affinity columns with amino acid substitution mutants, dominant-negative functional assays, transcription reporter assays The Journal of biological chemistry High 8051128
1996 CBF-B (NF-YA) interacts simultaneously with both subunits of the CBF-A–CBF-C heterodimer (NF-YB and NF-YC) to form a heterotrimeric molecule. The evolutionarily conserved histone-fold-like segment of CBF-C (NF-YC), homologous to H2A, is required for CBF-DNA complex formation and mediates interaction with CBF-A (NF-YB). Two separate domains in CBF-C interact with CBF-B (NF-YA), flanking the CBF-A interaction domain, suggesting a tridentate interaction surface. Cross-linking, immunoprecipitation, mutational analysis, yeast two-hybrid, in vitro DNA-binding assays Molecular and cellular biology High 8754798
1996 Transcriptional activation by the CBF/NF-Y heterotrimer is mediated by two distinct activation domains: one in CBF-B (NF-YB) and one in CBF-C (NF-YC); these act additively in vitro. CBF-A (NF-YA) itself does not contribute an activation domain in this assay. Both activation domains are glutamine- and hydrophobic-residue-rich, similar to Sp1. In vitro transcription reconstitution with purified recombinant CBF subunit deletion mutants in CBF-depleted nuclear extracts The Journal of biological chemistry High 8662945
2001 NF-YA protein is induced after DNA damage (MMS, UV, ionizing radiation) and directly binds to the CCAAT box in the GADD45 promoter. NF-YA binding at this CCAAT motif, together with Oct-1, is required for p53-independent induction of GADD45 transcription following DNA damage. EMSA, site-directed mutagenesis of promoter elements, Western blot of induced NF-YA protein, reporter gene assays Oncogene Medium 11420680
2003 NF-YA protein is induced by the DNA-alkylating agent MMS and directly binds to inverted CCAAT motifs in the hOGG1 promoter to activate OGG1 transcription; site-directed mutations of these CCAAT boxes abrogate promoter induction. Gel shift and supershift assay, site-directed mutagenesis, Western blot, luciferase reporter assay The Journal of biological chemistry Medium 14688259
2005 NF-Ya overexpression in primitive hematopoietic cells activates transcription of multiple HOX4 paralogs, Notch-1, LEF-1, and telomerase RNA, and HSCs overexpressing NF-Ya show increased in vivo repopulating ability after bone marrow transplantation, establishing NF-Ya as a regulator of HSC self-renewal. Retroviral overexpression, in vitro transcription assays, single/sequential bone marrow transplantation Proceedings of the National Academy of Sciences of the United States of America Medium 16081537
2008 NF-YA protein levels are regulated post-translationally by ubiquitylation and acetylation. Four C-terminal lysines are ubiquitylation targets (mutation stabilizes the protein). Two of these lysines are acetylated in vitro by p300, indicating competition between ubiquitylation and acetylation. A degradation-resistant NF-YA leads to sustained expression of mitotic cyclin complexes and increased cell proliferation. Site-directed mutagenesis of lysines, cycloheximide chase/stability assay, in vitro acetylation by p300, cell cycle and proliferation assays Molecular biology of the cell High 18815279
2009 Tuberin deficiency causes decreased NF-YA protein expression and redistribution of NF-YA from the nucleus to the cytoplasm, leading to loss of OGG1 transcription. Restoration of tuberin (via adenoviral Ad-TSC2) rescues nuclear NF-YA localization and OGG1 expression. siRNA knockdown, adenoviral rescue, Western blot, immunostaining/fractionation Journal of molecular signaling Medium 20040097
2010 Transcriptional activation of RGS4 in confluent PC6 cells is mediated by NF-YA binding to an inverted CCAAT box element (ICE) in the RGS4 promoter. NF-YA nuclear levels increase at confluence, acetylation of NF-YA increases, and dominant-negative NF-YA represses RGS4 promoter activity. NF-YA cooperates with C/EBPβ while Bcl6 (also acetylated) acts as a repressor at a nearby site. Chromatin immunoprecipitation, dominant-negative overexpression, luciferase reporter assay, Western blot of nuclear fractions The Journal of biological chemistry Medium 20630860
2010 TAT-fused NF-Ya protein enters the nucleus of human CD34+ hematopoietic cells and activates the NF-Ya target gene HOXB4, increasing proliferation 4-fold and enhancing engraftment in NOD-SCID IL2Rγ-null mice. Protein transduction (TAT fusion), real-time PCR, luciferase reporter, xenograft transplantation Blood Medium 20616221
2012 The short isoform of NF-YA (NF-YAs) is highly expressed in mouse ESCs and declines upon differentiation. A dominant-negative NF-YA mutant reduces expression of stem cell genes. NF-Y binding is required for NANOG association to its genomic loci (30–50% of NANOG peaks contain NF-Y sites). Protein transduction of TAT-NF-YAs compensates for LIF withdrawal in ESC cultures. Dominant-negative overexpression, protein transduction, bioinformatics analysis of ChIP-seq data, cell culture differentiation assays Stem cells (Dayton, Ohio) Medium 22969033
2013 NF-YA binds to two CCAAT boxes in the proximal EZH2 promoter in epithelial ovarian cancer (EOC) cells (enhanced compared to normal cells), and NF-YA knockdown downregulates EZH2 expression, decreases H3K27Me3 levels, and suppresses EOC cell growth in vitro and in a xenograft model. Chromatin immunoprecipitation (ChIP), siRNA knockdown, Western blot, luciferase reporter assay, xenograft mouse model Molecular cancer research : MCR Medium 23360797
2014 p21 directly binds NF-YA and inhibits CDK2–NF-YA interaction at the CCAAT box region of the PLK1 promoter. Upon adriamycin-induced DNA damage, p21 recruitment to this region displaces CDK2 and suppresses PLK1 transcription. NF-YA knockdown abolishes p21-mediated PLK1 repression and impairs p53-mediated protection from mitotic death. Co-immunoprecipitation, in vitro direct binding assay, chromatin immunoprecipitation, luciferase reporter assay, siRNA knockdown Cell death & disease High 24407240
2014 Paeoniflorin (PF) significantly increases NF-YA expression, which upregulates molecules of the ubiquitin-proteasome system (molecular chaperones, CHIP) and autophagy (TFEB), promoting clearance of mutant androgen receptor in SBMA models. Western blot, behavioral/pathological assays in SBMA mouse model, cell-based assays Human molecular genetics Low 24549037
2015 ZHX2 interacts with NF-YA (co-IP) and reduces NF-Y binding to the MDR1 promoter (ChIP), thereby repressing NF-Y-mediated MDR1 transcription. Knockdown of NF-YA or mutation of the NF-Y binding site in the MDR1 promoter eliminates ZHX2-mediated repression. Co-immunoprecipitation, chromatin immunoprecipitation, luciferase reporter assay, siRNA knockdown, mutagenesis Oncotarget Medium 25473899
2016 NF-YA overexpression upregulates EZH2 expression in melanoma cells, leading to enhanced STAT3 methylation/activation and increased VEGF secretion and angiogenesis. EZH2 knockdown attenuates NF-YA-induced angiogenesis. Overexpression/knockdown, Western blot, VEGF ELISA, in vitro angiogenesis assays Oncology reports Low 27109360
2016 The two NF-YA splice isoforms have distinct roles in myoblast fate: NF-YAs enhances proliferation while NF-YAl boosts differentiation. NF-YAl directly activates Mef2D, Six genes, and p57kip2 (Cdkn1c) via NF-Y binding to CCAAT promoters; it also reduces expression of lncRNA Kcnq1ot1, a negative regulator of Cdkn1c transcription. Overexpression of isoforms, expression profiling, bioinformatic analysis of CCAAT in regulated promoters, NF-Y binding assay Biochimica et biophysica acta Medium 26921500
2018 NF-YA contains two cell-penetrating peptide (CPP) sequences within its DNA-binding alpha-helices (A1 and A2), overlapping with nuclear localization signals, that allow nanomolar-concentration entry into cells without carrier peptides. Internalized NF-YA trimerizes with NF-YB/NF-YC and binds to CCAAT target DNA. Protein transfection into C2C12 myoblasts inhibits differentiation to myotubes. Protein transduction experiments, mutagenesis of CPP regions, EMSA for DNA binding after transduction, C2C12 differentiation assay Biochimica et biophysica acta. Molecular cell research Medium 30296497
2018 Ser320 of NF-YA (phosphorylatable by CDK2) makes structural contacts with the DNA phosphate backbone. Ser320 phosphorylation is the major NF-YA phospho-isoform in HeLa cells, increases upon mitotic arrest, and Ser320Ala/Glu mutants reduce DNA binding (EMSA) and transactivation of CCAAT-dependent MDR1 and RHOB promoters. Ser326 phosphorylation does not affect DNA binding. EMSA with Ala/Glu phosphomimetic mutants, transactivation assays, high-throughput proteomics phospho-site confirmation, phylogenetic analysis FASEB journal : official publication of the Federation of American Societies for Experimental Biology High 30589568
2019 NF-YA directly binds the CCAAT box in the SOX2 promoter (confirmed by EMSA and ChIP) and transcriptionally activates SOX2 expression in cervical cancer stem cells; overexpression of NF-YA in SiHa and C33A cells increases SOX2 transcription and protein. Dual-luciferase reporter assay, mutagenesis, EMSA, chromatin immunoprecipitation, overexpression PloS one Medium 31365524
2019 NF-YA overexpression confers resistance to glutamine deprivation by increasing GLUL mRNA/protein expression (key glutamine biosynthetic enzyme) and preventing activation of pro-apoptotic CHOP/DDIT3. GLUL inhibitors suppress the NF-YA-mediated protective effect. Elevated SERCA1/2 levels in NF-YA OE cells correlate with resistance to thapsigargin. Stable overexpression clones, cell death assays, RT-PCR/Western blot, pharmacological inhibition Biochimica et biophysica acta. Molecular cell research Medium 31706909
2020 NF-YA directly binds the CCAAT box in the SOX2 promoter in cervical cancer cells (confirmed by ChIP and EMSA), transactivating SOX2 expression and promoting cell proliferation and tumorigenic properties; knockdown of NF-YA reduces SOX2 expression. Luciferase reporter assay, site-directed mutagenesis, qChIP, EMSA, siRNA knockdown Journal of cellular and molecular medicine Medium 32954681
2020 NFYA directly binds the promoter regions of CDK4 and cyclin D1 (CCND1) in ccRCC cells, transactivating their expression, leading to RB phosphorylation and E2F pathway activation, thereby promoting G1/S cell cycle progression. ChIP, luciferase reporter assay, siRNA knockdown, cell cycle analysis American journal of cancer research Medium 32905496
2021 Metabolic syndrome-induced mitochondrial ROS enhance miR-193b expression, which degrades NFYA mRNA, reducing NFYA protein levels and consequently decreasing sGCβ1 expression and cGMP signaling in pulmonary artery smooth muscle cells. Forced AAV6-mediated NFYA overexpression restores sGCβ1 levels and ameliorates exercise-induced pulmonary hypertension in obese rats. miRNA overexpression/inhibition, AAV6 gene delivery in vivo, Western blot, cell culture with metabolic stress inducers Circulation Medium 34157861
2021 NFYA functions as a transcriptional activator of HOXB4 in hematopoietic progenitor cells, with TAT-NF-Ya protein transduction into CD34+ cells activating HOXB4 transcription (confirmed by luciferase reporter) and increasing proliferation and engraftment. Protein transduction, real-time PCR, luciferase reporter assay Methods in molecular biology (Clifton, N.J.) Low 22914950
2021 NF-YA isoform NF-YAl overexpression increases cell motility while NF-YAs enhances proliferation in prostate cancer 3D spheroids and xenografts, and NF-YA depletion reduces tumorigenic potential both in vitro and in vivo; NF-YAs transcript levels are higher in aggressive PCa and in LumB subtype. Lentiviral transduction, CRISPR-Cas9 depletion, 3D spheroid assays, RNA-seq profiling, xenograft in vivo Journal of experimental & clinical cancer research : CR Medium 34782004
2022 NFYAv1 (long-form isoform) upregulates transcription of lipogenic enzymes ACACA and FASN in triple-negative breast cancer (TNBC), enhancing malignant behavior in vitro and in vivo. Loss of the NFYAv1-lipogenesis axis strongly suppresses malignant behavior; Nfyav1-deficient mice show no developmental abnormalities. Isoform-specific overexpression/knockdown, in vitro proliferation/invasion assays, in vivo tumor model, RT-PCR/Western blot Communications biology Medium 37268670
2022 NFYA transcriptionally activates EHMT2-repressed ALDH2 (cooperatively with NFYA overexpression and EHMT2 inhibition) in NSCLC cells, and ALDH2 overexpression activates the RAS/RAF oncogenic pathway contributing to paclitaxel resistance. Gene microarray, siRNA/overexpression, cell viability assay, xenograft model Molecular cancer Low 35477569
2022 NFYAv2 (short-form isoform) upregulates transcription of gluconeogenic enzyme PCK1 in hepatocellular carcinoma (HCC), inducing high ROS levels and energy crisis promoting cell death with anti-tumor effects. Nfyav1-deficient mice spontaneously overexpress Nfyav2 but show no increased gluconeogenesis in the liver. Isoform-specific overexpression, RT-PCR/Western blot, ROS measurement, in vitro cell death assays, mouse model Frontiers in cell and developmental biology Medium 36092708
2023 NFYa, interacting with cofactor SP2, activates genes linking metabolism and proliferation at the transcriptional level in developing mouse cardiomyocytes. NFYa deletion (nestin-Cre not applicable here; cardiac-specific deletion) causes reduced cardiomyocyte proliferation, impaired mitochondrial metabolism, cardiac growth defects and embryonic death. Spatial and single-cell transcriptomics identify decreased immature regenerative cardiomyocytes and increased trabecular/mature cardiomyocytes. Conditional knockout mouse, spatial transcriptomics, single-cell transcriptomics, ChIP/co-factor interaction (SP2), metabolic assays Developmental cell High 37972593
2023 NF-YA (short isoform) is the dominant isoform in neural progenitors and co-expressed with cell cycle genes. Conditional deletion of NF-YA in neural progenitors (nestin-Cre) causes thinning of the cerebral cortex, loss of striatum, progressive decline in neural progenitors, increased apoptosis, and reduced proliferation. ChIP-seq reveals preferential NF-Y binding to cell cycle gene promoters. Forced expression of the long NF-YA isoform in neural progenitors reduces neuronal count, revealing an isoform switch during neuronal differentiation. Conditional knockout mouse (nestin-Cre), ChIP-seq, spatial and single-cell transcriptomics, immunohistochemistry, long-isoform overexpression The Journal of biological chemistry High 38199563
2024 PKM1 sustains ATP levels to inhibit AMPK, which otherwise phosphorylates and destabilizes NFYa. In Pkm1 mutant embryos, AMPK is activated, NFYa is phosphorylated and destabilized, reducing cardiomyocyte proliferation and causing thin myocardium and perinatal lethality. This defines a PKM1-AMPK-NFYa axis linking energy metabolism to cell cycle control in the embryonic heart. Point mutation Pkm1 mouse model, Western blot for AMPK/NFYa phosphorylation, cardiomyocyte proliferation assays, cardiac phenotyping National science review Medium 41536305
2024 NFYA transcriptionally suppresses PEBP1 expression in lung adenocarcinoma cells by binding to the PEBP1 promoter (confirmed by dual-luciferase reporter and ChIP), thereby inhibiting ferroptosis (reducing MDA, Fe2+, and lipid ROS). Dual-luciferase reporter assay, chromatin immunoprecipitation, overexpression/knockdown, ferroptosis marker assays (MDA, Fe2+, lipid ROS) Mutation research Medium 38996537
2025 circPTK2 binds MDM2 in the cytoplasm, preventing MDM2 from interacting with and ubiquitylating NFYA. This stabilizes NFYA, which then binds the FOXM1 promoter to upregulate FOXM1 and suppress cellular senescence in NSCLC cells. Co-immunoprecipitation, ChIP, dual-luciferase reporter assay, siRNA knockdown, RNA-seq British journal of pharmacology Medium 41204684
2025 NFYA mediates BRD2 upregulation in response to BET inhibitor treatment; NFYA depletion attenuates BRD2 upregulation upon BETi, establishing NFYA as a transcriptional regulator of the BRD2 adaptive resistance mechanism. siRNA knockdown of NFYA, Western blot/RT-PCR of BRD2, ChIP-seq (BRD2/BRD4), cancer cell line models bioRxivpreprint Low
2026 NFYA acts as a pioneer factor at meiotic gene promoters in pre-meiotic germ cells: conditional germline deletion of Nfya in male mice blocks meiotic entry. Single-cell ATAC-seq shows loss of chromatin accessibility at meiotic gene promoters (including those regulated by STRA8/MEISON) upon NFYA deletion. Conditional germline knockout (Nfya), single-cell ATAC-seq, spatial transcriptomics The EMBO journal High 41857150
2026 NFYA regulates two sequential waves of transcriptional activation during oocyte-to-embryo transition: primordial follicle oocyte activation (PFA) and zygotic genome activation (ZGA). Oocyte-specific Nfya deletion impairs open chromatin establishment and transcription during PFA, causing ferroptosis and early folliculogenesis failure. Acute NFYA depletion in zygotes causes defective ZGA and two-cell embryo arrest. During PFA, NFYA predominantly binds promoters; during ZGA, it predominantly binds enhancers, though it consistently targets chaperone and histone gene promoters in both stages. Oocyte-specific conditional knockout, ATAC-seq (chromatin accessibility), RNA-seq, zygote acute depletion bioRxivpreprint Medium 41959188
2007 In Drosophila, NF-YA (dNF-YA) overexpression with eyeless-GAL4 causes headless lethality, enhanced by reduction of eyeless gene dose and suppressed by reduction of Distal-less gene dose, placing dNF-YA in the eye disc specification pathway downstream of or parallel to eyeless/Distal-less. Crossing dNF-YA-overexpressing flies with Notch mutants had no apparent effect. Transgenic Drosophila overexpression/RNAi, genetic epistasis (dosage reduction of eyeless, Distal-less, Notch) Genesis (New York, N.Y. : 2000) Medium 17216611
2021 C. elegans NFYA-1 (T08D10.1) acts as an in vitro substrate for activated ERK MAP kinase and its DNA-binding activity is reduced after ERK treatment. Genetic analysis places nfya-1 as inhibiting vulval development, acting downstream or in parallel to let-60/ras. In vitro kinase assay with purified NFYA-1, DNA-binding activity assay post-ERK treatment, genetic epistasis with let-60/ras mutants Cells & development Medium 34838796
2007 GATA, NF-YA, and CREB form a complex that binds the overlapping GATA/NF-Y motif in the claudin-11 promoter in vivo to promote transcription. siRNA against NF-YA reduces claudin-11 reporter activity. Smad3/4 can displace this complex and repress transcription by recruiting HDAC1 and mSin3A. EMSA, chromatin immunoprecipitation, siRNA knockdown, luciferase reporter assay Journal of cellular physiology Medium 17226765

Source papers

Stage 0 corpus · 87 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 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. Proceedings of the National Academy of Sciences of the United States of America 253 7878029
2009 Members of miR-169 family are induced by high salinity and transiently inhibit the NF-YA transcription factor. BMC molecular biology 217 19351418
1994 Dominant negative analogs of NF-YA. The Journal of biological chemistry 191 8051128
1996 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. Molecular and cellular biology 130 8754798
2001 Transcription factors Oct-1 and NF-YA regulate the p53-independent induction of the GADD45 following DNA damage. Oncogene 92 11420680
2015 The NF-YA transcription factor OsNF-YA7 confers drought stress tolerance of rice in an abscisic acid independent manner. Plant science : an international journal of experimental plant biology 87 26706071
2005 NF-Ya activates multiple hematopoietic stem cell (HSC) regulatory genes and promotes HSC self-renewal. Proceedings of the National Academy of Sciences of the United States of America 86 16081537
2016 NUCLEAR FACTOR Y, Subunit A (NF-YA) Proteins Positively Regulate Flowering and Act Through FLOWERING LOCUS T. PLoS genetics 73 27977687
1996 The transcriptional activity of the CCAAT-binding factor CBF is mediated by two distinct activation domains, one in the CBF-B subunit and the other in the CBF-C subunit. The Journal of biological chemistry 70 8662945
2021 Metabolic Syndrome Mediates ROS-miR-193b-NFYA-Dependent Downregulation of Soluble Guanylate Cyclase and Contributes to Exercise-Induced Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction. Circulation 67 34157861
2022 An EHMT2/NFYA-ALDH2 signaling axis modulates the RAF pathway to regulate paclitaxel resistance in lung cancer. Molecular cancer 57 35477569
2020 miR169c-NFYA-C-ENOD40 modulates nitrogen inhibitory effects in soybean nodulation. The New phytologist 54 33245793
2018 LINC01016 promotes the malignant phenotype of endometrial cancer cells by regulating the miR-302a-3p/miR-3130-3p/NFYA/SATB1 axis. Cell death & disease 54 29467441
2013 NF-YA underlies EZH2 upregulation and is essential for proliferation of human epithelial ovarian cancer cells. Molecular cancer research : MCR 52 23360797
2012 The short isoform of NF-YA belongs to the embryonic stem cell transcription factor circuitry. Stem cells (Dayton, Ohio) 49 22969033
2008 Posttranslational regulation of NF-YA modulates NF-Y transcriptional activity. Molecular biology of the cell 49 18815279
2003 Transcription factors NF-YA regulate the induction of human OGG1 following DNA-alkylating agent methylmethane sulfonate (MMS) treatment. The Journal of biological chemistry 44 14688259
2022 NF-YA transcription factors suppress jasmonic acid-mediated antiviral defense and facilitate viral infection in rice. PLoS pathogens 43 35560151
2019 Overexpression and alternative splicing of NF-YA in breast cancer. Scientific reports 43 31506469
2007 Dual transcriptional control of claudin-11 via an overlapping GATA/NF-Y motif: positive regulation through the interaction of GATA, NF-YA, and CREB and negative regulation through the interaction of Smad, HDAC1, and mSin3A. Journal of cellular physiology 40 17226765
2018 Genome-wide characterization and expression analysis of citrus NUCLEAR FACTOR-Y (NF-Y) transcription factors identified a novel NF-YA gene involved in drought-stress response and tolerance. PloS one 36 29906271
2010 TAT-mediated transduction of NF-Ya peptide induces the ex vivo proliferation and engraftment potential of human hematopoietic progenitor cells. Blood 36 20616221
2016 NF-YA splice variants have different roles on muscle differentiation. Biochimica et biophysica acta 33 26921500
2002 Synergistic regulation of human cystathionine-beta-synthase-1b promoter by transcription factors NF-YA isoforms and Sp1. Biochimica et biophysica acta 33 12427542
2015 ZHX2 enhances the cytotoxicity of chemotherapeutic drugs in liver tumor cells by repressing MDR1 via interfering with NF-YA. Oncotarget 32 25473899
2023 CDCA8 induced by NF-YA promotes hepatocellular carcinoma progression by regulating the MEK/ERK pathway. Experimental hematology & oncology 30 36639822
2020 NF-YA Overexpression in Lung Cancer: LUAD. Genes 29 32075093
2014 Paeoniflorin eliminates a mutant AR via NF-YA-dependent proteolysis in spinal and bulbar muscular atrophy. Human molecular genetics 29 24549037
2019 NF-YA Overexpression in Lung Cancer: LUSC. Genes 27 31744190
2018 Curcumin ameliorates PRMT5-MEP50 arginine methyltransferase expression by decreasing the Sp1 and NF-YA transcription factors in the A549 and MCF-7 cells. Molecular and cellular biochemistry 27 30392062
2019 The carcinogen cadmium elevates CpG-demethylation and enrichment of NFYA and E2F1 in the promoter of oncogenic PRMT5 and EZH2 methyltransferases resulting in their elevated expression in vitro. Chemosphere 25 31675590
2020 Transcription factor NFYA promotes G1/S cell cycle transition and cell proliferation by transactivating cyclin D1 and CDK4 in clear cell renal cell carcinoma. American journal of cancer research 24 32905496
2023 Transcription factor NFYa controls cardiomyocyte metabolism and proliferation during mouse fetal heart development. Developmental cell 22 37972593
2021 Alternative splicing of NF-YA promotes prostate cancer aggressiveness and represents a new molecular marker for clinical stratification of patients. Journal of experimental & clinical cancer research : CR 22 34782004
2016 NF-YA promotes invasion and angiogenesis by upregulating EZH2-STAT3 signaling in human melanoma cells. Oncology reports 22 27109360
2007 Complex interference in the eye developmental pathway by Drosophila NF-YA. Genesis (New York, N.Y. : 2000) 21 17216611
2021 KLF5 and NFYA factors as novel regulators of prostate cancer cell metabolism. Endocrine-related cancer 20 33690159
2019 Long noncoding RNA PANDA promotes esophageal squamous carcinoma cell progress by dissociating from NF-YA but interact with SAFA. Pathology, research and practice 18 31495606
2022 miR-140-3P Induces Chemotherapy Resistance in Esophageal Carcinoma by Targeting the NFYA-MDR1 Axis. Applied biochemistry and biotechnology 17 36255597
2020 NF-YA promotes the cell proliferation and tumorigenic properties by transcriptional activation of SOX2 in cervical cancer. Journal of cellular and molecular medicine 17 32954681
2023 NFYA promotes malignant behavior of triple-negative breast cancer in mice through the regulation of lipid metabolism. Communications biology 16 37268670
2000 Possible role of subunit A of nuclear factor Y (NF-YA) in normal human diploid fibroblasts during senescence. Biogerontology 16 11707903
2020 Genome-wide identification of NF-YA gene family in cotton and the positive role of GhNF-YA10 and GhNF-YA23 in salt tolerance. International journal of biological macromolecules 15 33080263
2019 NF-YA transcriptionally activates the expression of SOX2 in cervical cancer stem cells. PloS one 15 31365524
2014 Association of p21 with NF-YA suppresses the expression of Polo-like kinase 1 and prevents mitotic death in response to DNA damage. Cell death & disease 14 24407240
2016 Transcription factor NF‑YA promotes a malignant phenotype by upregulating fatty acid synthase expression. Molecular medicine reports 13 27840951
2022 Identification and expression analysis of maize NF-YA subunit genes. PeerJ 12 36389434
2016 Advances on plant miR169/NF-YA regulation modules. Yi chuan = Hereditas 12 27531608
1996 Cloning of Schistosoma mansoni transcription factor NF-YA subunit: phylogenic conservation of the HAP-2 homology domain. Molecular and biochemical parasitology 12 8813662
2018 The phosphorylatable Ser320 of NF-YA is involved in DNA binding of the NF-Y trimer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 11 30589568
2010 A novel mechanism involving coordinated regulation of nuclear levels and acetylation of NF-YA and Bcl6 activates RGS4 transcription. The Journal of biological chemistry 11 20630860
2022 NFYA promotes the anti-tumor effects of gluconeogenesis in hepatocellular carcinoma through the regulation of PCK1 expression. Frontiers in cell and developmental biology 9 36092708
2004 Down-regulation of human topoisomerase IIalpha correlates with altered expression of transcriptional regulators NF-YA and Sp1. Anti-cancer drugs 9 15057140
2003 Dexamethasone inhibits transforming growth factor-beta receptor (Tbeta R) messenger RNA expression in hamster preantral follicles: possible association with NF-YA. Biology of reproduction 9 12606399
2009 Molecular mechanism of regulation of OGG1: tuberin deficiency results in cytoplasmic redistribution of transcriptional factor NF-YA. Journal of molecular signaling 8 20040097
2024 Transcription factor NFYA inhibits ferroptosis in lung adenocarcinoma cells by regulating PEBP1. Mutation research 7 38996537
2022 Phylogeny of NF-YA trans-activation splicing isoforms in vertebrate evolution. Genomics 7 35589059
2014 The repair of oxidized purines in the DNA of human lymphocytes requires an activation involving NF-YA-mediated upregulation of OGG1. DNA repair 7 25463392
2023 PDGFRβ Activation Induced the Bovine Embryonic Genome Activation via Enhanced NFYA Nuclear Localization. International journal of molecular sciences 6 38069370
2020 SSEA3 and Sialyl Lewis a Glycan Expression Is Controlled by B3GALT5 LTR through Lamin A-NFYA and SIRT1-STAT3 Signaling in Human ES Cells. Cells 6 31936807
2019 NF-YA overexpression protects from glutamine deprivation. Biochimica et biophysica acta. Molecular cell research 6 31706909
2018 25-hydroxycholesterol down-regulates oxysterol binding protein like 2 (OSBPL2) via the p53/SREBF2/NFYA signaling pathway. The Journal of steroid biochemistry and molecular biology 6 30391516
2025 SNORD9 promotes ovarian cancer tumorigenesis via METTL3/IGF2BP2-mediated NFYA m6A modification and is a potential target for antisense oligonucleotide therapy. Life sciences 5 40044032
2024 The transcription factor NF-YA is crucial for neural progenitor maintenance during brain development. The Journal of biological chemistry 5 38199563
2024 Coptisine-mediated downregulation of E2F7 induces G2/M phase arrest in hepatocellular carcinoma cells through inhibition of E2F4/NFYA/NFYB transcription factors. Chemico-biological interactions 4 38795876
2021 Nfya-1 functions as a substrate of ERK-MAP kinase during Caenorhabditis elegans vulval development. Cells & development 4 34838796
1996 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. The Biochemical journal 4 8760361
2021 Rapid excavating a FLOWERING LOCUS T-regulator NF-YA using genotyping-by-sequencing. Molecular breeding : new strategies in plant improvement 3 37309386
2022 Genome-Wide Identification and Characterization of the NF-YA Gene Family and Its Expression in Response to Different Nitrogen Forms in Populus × canescens. International journal of molecular sciences 2 36232523
2018 NF-YA enters cells through cell penetrating peptides. Biochimica et biophysica acta. Molecular cell research 2 30296497
2012 NF-Ya protein delivery as a tool for hematopoietic progenitor cell expansion. Methods in molecular biology (Clifton, N.J.) 2 22914950
2025 PKM1 is required for embryonic cardiomyocyte proliferation through energetic regulation of NFYa stability. National science review 1 41536305
2024 JARID2 activation by NFYA promotes stemness of triple-negative breast cancer cells through the PI3K/AKT pathway. Expert review of anticancer therapy 1 39254227
2023 NF-YA isoforms with alternative splicing of exon-5 in Aves. Genomics 1 37536396
2026 NFYA transcriptionally activates GPX4 inhibiting ferroptosis in colorectal cancer. Tissue & cell 0 41544530
2026 Transcription factor NFYA directs male meiotic entry by regulating accessible chromatin at meiotic promoters in mice. The EMBO journal 0 41857150
2026 NFYA regulates two sequential genome-wide transcriptional activation events during oocyte to embryo transition. bioRxiv : the preprint server for biology 0 41959188
2026 NFYA-Mediated TTK Up-Regulation Drives Fast Cell Cycle Progression and Its Inhibition Leads to Mitotic Catastrophe in Triple Negative Breast Cancer. Cancers 0 42122120
2026 Genome-Wide Identification of NF-YA Transcription Factors in Strawberry and Their Responses to Salt Stress. Plants (Basel, Switzerland) 0 42197610
2026 NFYA Activates REG1A Expression to Promote Malignant Progression and Chemosensitivity in Rectal Cancer. Annals of clinical and laboratory science 0 42259544
2025 Multiple Retrotransposon-mediated NF-YA Gene Duplication Events Recurred in Diverse Groups of Mammals at Different Ancestry Levels. Genome biology and evolution 0 40408078
2025 Tr-KIT Downstream Regulation by YY1 and NFYA Transcription Factors Knockdown in Prostate Cancer Cells. Genes, chromosomes & cancer 0 40716089
2025 A gene-expression signature defines a subtype of Stomach Adenocarcinomas with low levels of Claudins and a high ratio of NF-YA long/NF-YA short splicing variants. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 0 41082105
2025 Comprehensive Analysis of Miscanthus NF-YA Genes Reveals Potential Involvement in Drought Stress Adaptation. Plants (Basel, Switzerland) 0 41095241
2025 CircPTK2 enhances non-small cell lung cancer proliferation by inhibiting cellular senescence through stabilizing NFYA and elevating FOXM1. British journal of pharmacology 0 41204684
2024 Clinical relevance of NFYA splice variants in patients with acute myeloid leukaemia undergoing intensive chemotherapy. British journal of haematology 0 39192759
2024 NFYA-mediated promotion of castration-resistant prostate cancer progression through EGR4 regulation. Discover oncology 0 39367986

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