Affinage

NFIC

Nuclear factor 1 C-type · UniProt P08651

Length
508 aa
Mass
55.7 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NFIC (CTF/NF-I) is a sequence-specific transcription factor that recognizes CCAAT/NFI elements through an N-terminal domain that simultaneously mediates DNA binding and dimerization, while transcriptional activation is driven by a separate C-terminal proline-rich domain representing a distinct class of activation domain (PMID:2504497). Activation proceeds through a CTD-like motif within this proline-rich region that directly contacts TBP, and mutations that abolish activation reduce TBP affinity (PMID:8029001); activity additionally depends on affinity-purified cofactors that counteract squelching and antagonize histone H1-mediated repression of basal transcription (PMID:1406693). Beyond transcription, NFIC stimulates viral DNA replication: it binds the adenovirus origin, directly interacts with the pTP-pol complex, and bends origin DNA by 60°, with concerted bending alongside Oct-1 synergistically enhancing replication (PMID:2214023, PMID:15576348), and it likewise stimulates polyomavirus (BKV) replication through interaction with Pol-primase and T antigen (PMID:22205750). NFIC activity is heavily controlled post-translationally: oxidation inactivates DNA binding via the regulatory Cys-3 in the DNA-binding domain (PMID:7961993) and represses transactivation via Cys-427 in the activation domain (PMID:10794737), TGF-β/calcium/calcineurin signaling induces its activation domain (PMID:9295299), N-glycosylation generates a distinct isoform during mammary involution that alters chromatin occupancy (PMID:11991954), and zinc-dependent Smad2/3 binding sequesters it in the cytoplasm (PMID:22228435). In vivo, NFIC is essential for postnatal tooth root formation, where its loss disrupts odontoblast differentiation, polarity, and intercellular junctions (PMID:12529411, PMID:17760551). It acts downstream of a Smad4-Shh cascade (PMID:19888897) and directly activates the KLF4, Osterix, and Hhip promoters to coordinate odontoblast/osteoblast differentiation and attenuate Hedgehog signaling (PMID:24801901, PMID:25138274, PMID:26293299), with its protein levels set by METTL3-mediated m6A modification of its mRNA (PMID:32936965). NFIC also functions context-dependently as a repressor, silencing the p21/CDKN1A promoter (PMID:17130157) and, through specific isoforms, repressing cyclin D1 (PMID:33824311) and competing with C/EBPβ to regulate PD-L1 expression (PMID:38528526).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1989 High

    Established the modular architecture of NFIC by showing DNA binding/dimerization and transcriptional activation reside in physically separable domains, defining the proline-rich domain as a new activation-domain class.

    Evidence cDNA mutant expression in E. coli and Drosophila cells with functional domain dissection

    PMID:2504497

    Open questions at the time
    • Did not identify the activation-domain target factor
    • No structural model of the DNA-binding domain
  2. 1990 High

    Resolved how NFIC stimulates adenovirus replication, showing it acts via a direct, pTP-pol-concentration-dependent protein contact distinct from the mechanism used by Oct-1.

    Evidence Reconstituted in vitro replication, DNase I footprinting, gel retardation, and glutaraldehyde cross-linking with purified proteins

    PMID:2214023 PMID:2767055

    Open questions at the time
    • Precise interaction surface on pTP-pol not mapped
    • Relevance to cellular replication not addressed
  3. 1994 High

    Defined the molecular basis of NFIC activation by identifying a CTD-like motif in the proline-rich domain that binds TBP, linking activation strength to TBP affinity.

    Evidence Deletion/point mutagenesis with in vitro TBP interaction and transcription assays

    PMID:8029001

    Open questions at the time
    • Whether TBP is the limiting cofactor from squelching studies not established
    • In vivo contribution not tested
  4. 1994 High

    Identified redox control of NFIC DNA binding, distinguishing structural cysteines required for binding from the oxidation-sensitive regulatory Cys-3.

    Evidence Site-directed mutagenesis with diamide/NEM treatment and DTT restoration in in vitro DNA-binding assays

    PMID:7961993

    Open questions at the time
    • Physiological oxidant signal not identified
    • No in vivo demonstration of redox switching
  5. 1992 High

    Showed NFIC-dependent transcription requires dedicated cofactors that relieve histone H1-mediated repression, situating NFIC activation in a chromatin context.

    Evidence Affinity purification of cofactors and in vitro reconstituted transcription with squelching experiments

    PMID:1406693

    Open questions at the time
    • Cofactor identities not molecularly defined
    • Link to the TBP-contacting motif unresolved
  6. 2000 High

    Extended redox regulation to the activation domain, identifying Cys-427 as the residue through which oxidative stress represses NFIC transactivation.

    Evidence GAL4-fusion transfection assays with systematic cysteine mutagenesis and H2O2/NEM treatment

    PMID:10794737

    Open questions at the time
    • Mechanism linking Cys-427 oxidation to reduced TBP/cofactor contact unknown
    • Cellular oxidant source unaddressed
  7. 1997 Medium

    Connected NFIC activity to signaling by demonstrating TGF-β induces its activation domain through a calcium/calcineurin/CaMKIV axis.

    Evidence Transfection of constitutively active calcineurin/CaMKIV, thapsigargin, and immunosuppressant inhibitors with TAD readout in NIH3T3 cells

    PMID:9295299

    Open questions at the time
    • Direct phosphorylation site on NFIC not identified
    • Calcineurin/CaMKIV substrate specificity not proven biochemically
  8. 2002 High

    Revealed glycosylation as a developmental regulator, with an N-glycosylated NFIC isoform appearing during mammary involution and altering target promoter occupancy.

    Evidence Western blot, concanavalin A binding, peptide N-glycosidase, and tunicamycin inhibition in vivo and in mammospheres

    PMID:11991954

    Open questions at the time
    • Glycosylation sites not mapped
    • Mechanism by which glycosylation enhances chromatin binding unresolved
  9. 2003 High

    Defined the principal in vivo function by showing Nfic knockout mice fail to form tooth roots despite normal crown development.

    Evidence Nfic gene disruption in mice with histological/morphological analysis

    PMID:12529411

    Open questions at the time
    • Direct transcriptional targets not yet identified at this stage
    • Cell-autonomous vs non-autonomous role unclear
  10. 2004 High

    Provided a structural mechanism for replication synergy, measuring NFIC-induced 60° origin bending that combines with Oct-1 bending to enhance replication.

    Evidence Scanning force microscopy with in vitro replication assays

    PMID:15576348

    Open questions at the time
    • Whether bending applies to cellular promoters not tested
    • Structural basis of bend not resolved at residue level
  11. 2007 Medium

    Localized the root defect to odontoblast differentiation, showing Nfic loss disrupts polarity, junctions, and dentin sialophosphoprotein expression while sparing the epithelial root sheath.

    Evidence Immunohistochemistry and in situ hybridization in Nfic knockout mice

    PMID:17760551 PMID:19153194

    Open questions at the time
    • Direct vs indirect control of junction genes (ZO-1, occludin) not distinguished here
    • Upstream inducer of Nfic not defined
  12. 2010 High

    Placed NFIC in a signaling hierarchy, establishing a Smad4-Shh-Nfic cascade in which ectopic Shh induces Nfic and partially rescues root formation.

    Evidence Tissue-specific Cre-lox knockout (K14-Cre;Smad4fl/fl), ectopic Shh delivery, and rescue with in situ hybridization

    PMID:19888897

    Open questions at the time
    • How Shh signaling induces Nfic transcription not defined
    • Direct Nfic targets downstream not identified in this study
  13. 2014 High

    Identified direct NFIC transcriptional targets in differentiation, showing it binds and activates the Osterix and KLF4 promoters to drive osteoblast/odontoblast programs.

    Evidence ChIP, luciferase reporters, siRNA, overexpression, and BMSC transplantation in Nfic-/- mice

    PMID:24801901 PMID:25138274

    Open questions at the time
    • Cofactors required at these promoters not defined
    • Combinatorial logic with other differentiation factors unresolved
  14. 2015 High

    Showed NFIC attenuates Hedgehog signaling during root development by directly activating the Hhip promoter, with Hh inhibition partially rescuing Nfic-/- phenotypes.

    Evidence ChIP, RNAscope, RNA-seq, Gli1 reporter mice, and pharmacological Hh inhibition in Nfic-/- mice

    PMID:26293299

    Open questions at the time
    • Feedback relationship between Shh-induced Nfic and Nfic-driven Hhip not fully resolved
    • Quantitative contribution of Hhip vs other targets unclear
  15. 2020 High

    Established post-transcriptional control of NFIC by showing METTL3-mediated m6A modification sets its translational efficiency and protein levels in odontoblasts.

    Evidence METTL3 conditional knockout, siRNA, m6A-seq, and NFIC rescue overexpression

    PMID:32936965

    Open questions at the time
    • m6A reader mediating translational effect not identified
    • Specific modified residues on NFIC mRNA not mapped
  16. 2021 Medium

    Demonstrated isoform-specific NFIC function in cancer, with MCPIP1-driven splicing producing CTF5 that represses cyclin D1 to block proliferation.

    Evidence MCPIP1 manipulation, splicing analysis, ChIP on cyclin D1 promoter, reporters, flow cytometry, and proliferation assays in TNBC cells

    PMID:33824311

    Open questions at the time
    • Structural basis of CTF5 repressive activity unknown
    • Generality across NFIC targets not established
  17. 2024 Medium

    Showed NFIC regulates immune-checkpoint expression by competing allele-specifically with C/EBPβ at the PD-L1 promoter/enhancer.

    Evidence Binding microarray, siRNA silencing, and luciferase reporters in NSCLC cell lines

    PMID:38528526

    Open questions at the time
    • In vivo relevance to tumor immunity not demonstrated
    • Direction-determining cofactors not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse post-translational and splicing controls (redox, glycosylation, calcium signaling, zinc/Smad sequestration, m6A, isoform switching) are integrated to select activator versus repressor behavior on specific promoters remains unresolved.
  • No unified model linking modifications to target-specific outcomes
  • Genome-wide occupancy and isoform-specific binding landscapes not defined
  • Structural basis of context-dependent activation vs repression unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-69306 DNA Replication 3
Partners
C/EBPBOCT-1SKISMAD2/3TBPTTF-2

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 The N-terminal portion of CTF/NF-I (CTF-1) is sufficient for site-specific DNA recognition, protein dimerization, and adenovirus replication, while transcriptional activation requires a distinct C-terminal proline-rich domain (~25% proline residues), representing a novel class of activation domain distinct from acidic or glutamine-rich motifs. cDNA mutant expression in E. coli and Drosophila cells, functional dissection of domain activities Cell High 2504497
1989 The adenovirus DNA binding protein (DBP) increases the affinity of NFI for its binding site in the replication origin by increasing the rate of NFI association and decreasing its dissociation rate, demonstrating cooperative protein-protein interaction that enhances adenovirus DNA replication. Gel retardation assays, kinetic binding analysis, purified protein co-incubation with reconstituted replication system The EMBO journal High 2767055
1990 NFI and NFIII/Oct-1 bind independently and without cooperative effects to their recognition sequences in the adenovirus origin, and each stimulates DNA replication through distinct mechanisms: NFI stimulation is strongly dependent on pTP-pol concentration and involves direct interaction with pTP-pol (shown by glutaraldehyde cross-linking), whereas NFIII/Oct-1 stimulation is concentration-independent. Reconstituted in vitro replication system with purified proteins, DNase I footprinting, gel retardation, glutaraldehyde cross-linking Journal of virology High 2214023
1989 Cytosine methylation within the CTF recognition site has no effect on CTF binding affinity in vitro, indicating that methylation-mediated transcriptional repression in vivo occurs through a mechanism other than directly blocking CTF binding. In vitro factor binding assays with methylated vs. unmethylated substrates, in vivo transcription assays Nucleic acids research Medium 2557588
1991 CTF/NF-I transactivates the grp78 promoter through interaction with a CCAAT motif-containing element (-129 to -90), mediating the stress-induced transcriptional response to malfolded proteins, glycosylation block, and calcium ionophore. 5' deletion, linker-scanning, and internal deletion mutations of grp78 promoter; transfection assays; protein-DNA interaction studies Molecular and cellular biology Medium 1656235
1991 CTF/NF-I proline-rich transcriptional activation domain synergizes with the estrogen receptor for transcriptional activation; synergism results from stronger tethering of a common limiting target factor, as both activators compete for the same limiting mediator demonstrated by in vivo competition experiments. Cotransfection in HeLa cells, GAL4-fusion proteins, in vivo competition assays Molecular and cellular biology Medium 2038313
1992 Purified cofactors with affinity for CTF-1 are required for CTF-1-regulated transcription in vitro, counteract squelching, and possess inhibitory activity for basal transcription relieved by the activator. Histone H1 represses basal transcription, and CTF-1 together with its cofactors antagonizes this histone-mediated repression. Affinity purification of cofactors, in vitro reconstituted transcription assays, squelching experiments Molecular and cellular biology High 1406693
1994 The proline-rich activation domain of CTF/NF-I contains a CTD-like motif (with sequence similarity to the RNA pol II heptapeptide repeat) essential for transcriptional activation; this motif mediates direct interaction with TATA-box-binding protein (TBP), and mutations abolishing transcriptional activation reduce TBP affinity. Deletion and point mutations of CTF/NF-I activation domain, in vitro direct interaction assays with TBP, transcription activation assays Nucleic acids research High 8029001
1994 Conserved cysteine residues Cys-2, Cys-4, and Cys-5 in the DNA-binding domain of NFI-C are essential for DNA binding (mutation abolishes binding), while Cys-3 is an oxidation-sensitive regulatory residue: diamide-mediated oxidation inactivates DNA binding of wild-type NFI, and mutation of Cys-3 confers resistance to oxidative inactivation. Site-directed mutagenesis, in vitro DNA-binding assays, N-ethylmaleimide and diamide treatment, DTT restoration experiments The Journal of biological chemistry High 7961993
1997 TGF-β induces the transcriptional activation domain (TAD) of CTF-1 via calcium signaling: TGF-β stimulates calcium influx in NIH3T3 cells, and constitutively active calcineurin or CaMKIV specifically induce CTF-1 TAD activity through the previously identified TGF-β-responsive domain; cyclosporin A and FK506 abolish calcineurin-mediated CTF-1 induction. Transfection with constitutively active calcineurin/CaMKIV, thapsigargin treatment, immunosuppressant inhibitors, TAD activation assays The Journal of biological chemistry Medium 9295299
1997 Ski oncoprotein physically binds NFI proteins and co-activates transcription of NFI-dependent reporters only in the presence of NFI; Ski homodimerization (via its C-terminal domain) is required for co-activation with NFI. SELEX for Ski DNA-binding sites, EMSA, co-activation transcription assays, domain deletion analysis Nucleic acids research Medium 9380514
1998 The four NFI isoforms (NFI-A, -B, -C, -X) differ in their maximal transcriptional activation potentials in a promoter-context-specific manner: NFI-X is the strongest activator of a simple NFI-Ad promoter, while NFI-B is strongest on the MMTV promoter. NFI heterodimers display intermediate activation potentials compared to homodimers. Transient transfection in JEG-3 cells with two model promoters, comparison of all four NFI genes and heterodimer combinations The Journal of biological chemistry Medium 9660824
1999 CTF/NF-I-C physically interacts with the forkhead transcription factor TTF-2 (via GST pull-down) and is required for hormone-induced TPO gene transcription; increasing the distance between CTF/NF1 and TTF-2 binding sites abolishes promoter activity. Moreover, CTF/NF-I-C protein levels are themselves induced by TSH, cAMP, and insulin. Transfection assays, protein-DNA interaction studies, GST pull-down, EMSA with specific antibodies The Journal of biological chemistry Medium 10329730
2000 Oxidative stress represses NFI/CTF transactivating function via a critical cysteine residue (Cys-427) in the transactivation domain: micromolar H2O2 represses the CTF-1 TAD in a dose-dependent manner, and mutation of Cys-427 to serine completely abolishes this repression. N-ethylmaleimide-mediated repression of transactivation is also Cys-427-dependent. GAL4-fusion proteins and transfection assays, systematic point mutations of cysteine/serine/tyrosine residues, H2O2 and NEM treatment The Biochemical journal High 10794737
2003 Genetic disruption of Nfic in mice results in specific tooth root development defects (molars lacking roots, abnormal incisors) while molar crown development is normal, establishing NFIC as an essential transcription factor specifically required for postnatal tooth root formation. Nfic gene disruption (knockout mice), histological and morphological analysis Molecular and cellular biology High 12529411
2004 NFI bends adenovirus origin DNA by 60° and Oct-1 bends it by 42°; simultaneous binding induces an 82° collective bend, and this concerted DNA bending leads to synergistic enhancement of DNA replication in functional assays. Scanning force microscopy, in vitro DNA replication assays Nucleic acids research High 15576348
2004 NFI chromatin binding at the MMTV promoter is cooperatively enhanced by glucocorticoid receptor (GR): co-expression of GR and NF1 in Xenopus oocytes reveals GR-NF1 cooperativity in DNA binding and chromatin remodeling. A fraction of NF1 sites are constitutively occupied (concentration-dependent) while hormone increases NF1 accessibility ~50-fold. Xenopus oocyte expression system, chromatin accessibility assays, co-expression experiments Molecular and cellular biology Medium 15024090
2005 PPARγ suppresses the alpha1(I) collagen promoter by inhibiting p300-facilitated NF-I binding to a proximal CCAAT box (-97/-85 bp); ChIP demonstrates that PPARγ inhibits NF-I binding to this site, and the NF-I site mutation nearly completely abrogates promoter activity. NF-I synergistically enhances Sp1-induced promoter activity. Deletion-reporter constructs, ChIP assay, DNA footprinting, promoter mutation analysis The Journal of biological chemistry Medium 16216869
2006 NFI functions as a transcriptional repressor of the p21 (CDKN1A) gene: ChIP and LMPCR identified a functional NFI binding site in the p21 basal promoter in vivo; mutations of this site increase promoter activity; RNAi-mediated NFI knockdown increases p21 promoter activity; overexpression of different NFI isoforms differentially affect cell cycle progression. LMPCR, ChIP, site-directed mutagenesis of p21 promoter, RNAi knockdown, transfection assays, cell cycle analysis Nucleic acids research High 17130157
2007 Nfic disruption does not affect formation of Hertwig's epithelial root sheath but causes severely disrupted odontoblast differentiation: Nfic-deficient odontoblasts lose intercellular junctions, polarity, and expression of dentin sialophosphoprotein, and form aberrant osteodentin-like roots with decreased cementoblasts. Immunohistochemistry, in situ hybridization, morphological analysis of Nfic knockout mice Journal of periodontology Medium 17760551
2009 Disruption of Nfic causes loss of intercellular junctions in odontoblasts, with decreased expression of tight junction proteins ZO-1 and occludin, leading to dissociation of odontoblasts, loss of cellular polarity, and formation of osteodentin-like mineralized tissue. Immunohistochemistry, RT-PCR, morphological analysis of Nfic knockout mice The journal of histochemistry and cytochemistry Medium 19153194
2010 TGF-β/BMP signaling through Smad4 in Hertwig's epithelial root sheath induces Shh expression, which in turn induces Nfic expression in cranial neural crest-derived dental mesenchyme; ectopic Shh induces Nfic expression and partially rescues root development in Smad4 conditional knockout mice, establishing a Smad4-Shh-Nfic signaling cascade. Tissue-specific Cre-lox knockout (K14-Cre;Smad4fl/fl mice), ectopic Shh delivery, in situ hybridization, rescue experiments Journal of bone and mineral research High 19888897
2011 BKV DNA replication is stimulated by NFI family members: NFI binds BKV origin sequences, NFIC/CTF1 stimulates BKV template replication in vitro at low DNA polymerase-α primase concentrations, and the p58 subunit of Pol-primase associates with NFIC/CTF1. NFI family members also interact with the helicase domain of BKV T antigen in pulldown assays. In vitro replication assay, pulldown assays, site-directed mutagenesis of NFI binding sites Journal of virology Medium 22205750
2002 NFIC undergoes N-glycosylation during mammary gland involution: a 74-kDa NFIC isoform (vs. 49-kDa during lactation) specifically binds concanavalin A, is sensitive to peptide N-glycosidase (reducing apparent size to ~63 kDa), and tunicamycin blocks its formation in vivo and in mammospheres. This glycosylated NFIC correlates with enhanced occupation of clusterin promoter NFI sites. Western blot with NFIC-specific antibodies, concanavalin A binding, peptide N-glycosidase treatment, tunicamycin inhibition in vivo (Elvax depot pellets) and in vitro The Journal of biological chemistry High 11991954
2012 Zinc modulates NFIC localization and activity during odontoblast differentiation: zinc enhances phosphorylation of Smad2/3 and increases NFI-C/p-Smad2/3 binding in the cytoplasm, retaining NFIC outside the nucleus; zinc deficiency causes nuclear accumulation of NFIC, which then binds to DSPP promoter and activates DSPP transcription and dentin mineralization. Western blot, subcellular fractionation, co-immunoprecipitation (NFI-C/p-Smad2/3), ChIP (DSPP promoter binding), luciferase reporter assays, zinc chelation/supplementation experiments Journal of cellular biochemistry Medium 22228435
2014 NFI-C directly regulates Osterix expression and acts downstream of the BMP-2-Runx2 pathway to control osteoblast differentiation in bone marrow stromal cells; transplantation of Nfic-overexpressing BMSCs stimulates new bone formation and inhibits adipocyte differentiation in Nfic-/- mice. Nfic knockout mice, BMSC transplantation, ChIP (Osterix promoter), siRNA knockdown, overexpression studies, in vivo bone formation assay Stem cells High 24801901
2014 NFIC directly binds to the KLF4 promoter (shown by ChIP) and stimulates Klf4 transcriptional activity, thereby regulating downstream Dmp1 and DSPP expression during odontoblast differentiation; Nfic also regulates E-cadherin promoter activity via KLF4 upregulation and suppresses Slug expression. ChIP, luciferase reporter assays, RT-PCR, immunohistochemistry in Nfic-/- mice The Journal of biological chemistry High 25138274
2015 Nfic regulates Hedgehog signaling during root development by directly binding to the Hhip promoter (shown by ChIP and RNAscope), activating Hhip (an Hh attenuator) expression; loss of Nfic elevates Hh signaling in dental mesenchyme and treatment of Nfic-/- mice with Hh inhibitor partially restores cell proliferation and root development. ChIP, RNAscope, RNA sequencing, Gli1 reporter mice, Hh inhibitor treatment, histological analysis of Nfic-/- and transgenic mice Development High 26293299
2020 METTL3-mediated m6A modification of NFIC mRNA controls its translational efficiency; loss of METTL3 reduces NFIC protein levels in odontoblasts, impairs tooth root formation and odontogenic differentiation, and this phenotype is partially rescued by overexpressing NFIC. METTL3 conditional knockout (Osterix-Cre), siRNA knockdown in human dental pulp cells, NFIC rescue overexpression, m6A sequencing Journal of bone and mineral research High 32936965
2021 MCPIP1 regulates NFIC alternative splicing to promote CTF5 (an NFIC isoform) synthesis in triple-negative breast cancer cells; CTF5 transcriptionally represses cyclin D1 expression and downregulates its downstream targets p-Rb and E2F1, thereby inhibiting cell cycle progression and proliferation. MCPIP1 overexpression/knockdown, splicing analysis, ChIP (cyclin D1 promoter), luciferase reporter assays, flow cytometry, in vitro and in vivo proliferation assays Cell death & disease Medium 33824311
2024 NFIC competitively binds to the PD-L1 promoter/enhancer region in an allele-specific manner (at rs822336 SNP site) and differentially regulates induction of PD-L1 expression; NFIC and C/EBPβ compete for binding to this region with opposing effects on PD-L1 expression, as demonstrated by binding microarray and silencing experiments. Binding microarray, siRNA silencing of NFIC and C/EBPβ, luciferase reporter assays, NSCLC cell line functional assays Molecular cancer Medium 38528526

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell 822 16325577
1989 The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain. Cell 763 2504497
2000 Roles of the NFI/CTF gene family in transcription and development. Gene 459 10831836
2019 Single-Cell RNA-Seq Analysis of Retinal Development Identifies NFI Factors as Regulating Mitotic Exit and Late-Born Cell Specification. Neuron 378 31128945
2013 Adaptor complex AP2/PICALM, through interaction with LC3, targets Alzheimer's APP-CTF for terminal degradation via autophagy. Proceedings of the National Academy of Sciences of the United States of America 201 24067654
2011 A small-molecule enhancer of autophagy decreases levels of Abeta and APP-CTF via Atg5-dependent autophagy pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 184 21368103
2016 Intraneuronal aggregation of the β-CTF fragment of APP (C99) induces Aβ-independent lysosomal-autophagic pathology. Acta neuropathologica 182 27138984
1990 Chicken NFI/TGGCA proteins are encoded by at least three independent genes: NFI-A, NFI-B and NFI-C with homologues in mammalian genomes. Nucleic acids research 172 2339052
2003 Essential role for NFI-C/CTF transcription-replication factor in tooth root development. Molecular and cellular biology 165 12529411
1990 The CHL 1 (CTF 1) gene product of Saccharomyces cerevisiae is important for chromosome transmission and normal cell cycle progression in G2/M. The EMBO journal 137 2265610
1991 Transactivation of the grp78 promoter by malfolded proteins, glycosylation block, and calcium ionophore is mediated through a proximal region containing a CCAAT motif which interacts with CTF/NF-I. Molecular and cellular biology 133 1656235
2010 Smad4-Shh-Nfic signaling cascade-mediated epithelial-mesenchymal interaction is crucial in regulating tooth root development. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 124 19888897
1992 A mammary cell-specific enhancer in mouse mammary tumor virus DNA is composed of multiple regulatory elements including binding sites for CTF/NFI and a novel transcription factor, mammary cell-activating factor. Molecular and cellular biology 109 1328867
2011 Global mapping of cell type-specific open chromatin by FAIRE-seq reveals the regulatory role of the NFI family in adipocyte differentiation. PLoS genetics 101 22028663
1990 Transcription factors NFI and NFIII/oct-1 function independently, employing different mechanisms to enhance adenovirus DNA replication. Journal of virology 99 2214023
2014 MicroRNA 21 (miR-21) and miR-181b couple with NFI-A to generate myeloid-derived suppressor cells and promote immunosuppression in late sepsis. Infection and immunity 96 24980967
2015 An Nfic-hedgehog signaling cascade regulates tooth root development. Development (Cambridge, England) 86 26293299
1991 Synergistic transcriptional activation by CTF/NF-I and the estrogen receptor involves stabilized interactions with a limiting target factor. Molecular and cellular biology 83 2038313
1994 Cloning and functional analysis of spliced isoforms of human nuclear factor I-X: interference with transcriptional activation by NFI/CTF in a cell-type specific manner. Nucleic acids research 76 7937100
2015 Partial BACE1 reduction in a Down syndrome mouse model blocks Alzheimer-related endosomal anomalies and cholinergic neurodegeneration: role of APP-CTF. Neurobiology of aging 74 26923405
1989 Cytosine methylation in CTF and Sp1 recognition sites of an HSV tk promoter: effects on transcription in vivo and on factor binding in vitro. Nucleic acids research 74 2557588
2020 NFI transcription factors provide chromatin access to maintain stem cell identity while preventing unintended lineage fate choices. Nature cell biology 71 32393888
1991 Identification of a fourth nuclear factor I gene in chicken by cDNA cloning: NFI-X. Nucleic acids research 67 1754401
1989 Co-operative interactions between NFI and the adenovirus DNA binding protein at the adenovirus origin of replication. The EMBO journal 67 2767055
2007 Nfic gene disruption inhibits differentiation of odontoblasts responsible for root formation and results in formation of short and abnormal roots in mice. Journal of periodontology 66 17760551
2000 Experimental analysis and computer prediction of CTF/NFI transcription factor DNA binding sites. Journal of molecular biology 65 10736221
1997 A combination of MEF3 and NFI proteins activates transcription in a subset of fast-twitch muscles. Molecular and cellular biology 65 9001219
1988 Analysis of transcription control elements of the mouse myelin basic protein gene in HeLa cell extracts: demonstration of a strong NFI-binding motif in the upstream region. Nucleic acids research 62 2463515
1994 Identification of a conserved oxidation-sensitive cysteine residue in the NFI family of DNA-binding proteins. The Journal of biological chemistry 61 7961993
2010 Phosphorylation of APP-CTF-AICD domains and interaction with adaptor proteins: signal transduction and/or transcriptional role--relevance for Alzheimer pathology. Journal of neurochemistry 60 21039524
2006 Transcriptional regulation of the cyclin-dependent kinase inhibitor 1A (p21) gene by NFI in proliferating human cells. Nucleic acids research 59 17130157
1996 A composite element binding the vitamin D receptor, retinoid X receptor alpha, and a member of the CTF/NF-1 family of transcription factors mediates the vitamin D responsiveness of the c-fos promoter. Molecular and cellular biology 59 8552086
1997 Regulation of the transforming growth factor beta-responsive transcription factor CTF-1 by calcineurin and calcium/calmodulin-dependent protein kinase IV. The Journal of biological chemistry 58 9295299
2009 NFI-A directs the fate of hematopoietic progenitors to the erythroid or granulocytic lineage and controls beta-globin and G-CSF receptor expression. Blood 55 19542302
1998 Nuclear factor I (NFI) isoforms differentially activate simple versus complex NFI-responsive promoters. The Journal of biological chemistry 55 9660824
2005 Peroxisome proliferator-activated receptor gamma suppresses proximal alpha1(I) collagen promoter via inhibition of p300-facilitated NF-I binding to DNA in hepatic stellate cells. The Journal of biological chemistry 54 16216869
1994 The upstream activator CTF/NF1 and RNA polymerase II share a common element involved in transcriptional activation. Nucleic acids research 53 8029001
2014 NFI-C regulates osteoblast differentiation via control of osterix expression. Stem cells (Dayton, Ohio) 51 24801901
1998 Endonuclease V (nfi) mutant of Escherichia coli K-12. Journal of bacteriology 51 9422591
1996 The CCAAT-binding proteins CP1 and NF-I cooperate with ATF-2 in the transcription of the fibronectin gene. The Journal of biological chemistry 51 8703044
1997 NFI-B3, a novel transcriptional repressor of the nuclear factor I family, is generated by alternative RNA processing. The Journal of biological chemistry 48 9099724
1994 Complex organization of CTF/NF-I, C/EBP, and HNF3 binding sites within the promoter of the liver-specific vitellogenin gene. The Journal of biological chemistry 48 7806524
1991 NF-I proteins from brain interact with the proenkephalin cAMP inducible enhancer. Nucleic acids research 47 1828294
1990 Regulation of brain-specific transcription of the mouse myelin basic protein gene: function of the NFI-binding site in the distal promoter. Biochemical and biophysical research communications 47 1690988
2010 A major role of p95/611-CTF, a carboxy-terminal fragment of HER2, in the down-modulation of the estrogen receptor in HER2-positive breast cancers. Cancer research 46 20978202
2004 Co-expressed presenilin 1 NTF and CTF form functional gamma-secretase complexes in cells devoid of full-length protein. Journal of neurochemistry 46 15030388
2000 GSK3 beta forms a tetrameric complex with endogenous PS1-CTF/NTF and beta-catenin. Effects of the D257/D385A and FAD-linked mutations. Annals of the New York Academy of Sciences 45 11193155
1992 Purified cofactors and histone H1 mediate transcriptional regulation by CTF/NF-I. Molecular and cellular biology 45 1406693
2003 The clinical outcome of patients with stage Ia1 and Ia2 squamous cell carcinoma of the uterine cervix: a Cooperation Task Force (CTF) study. European journal of gynaecological oncology 44 14658592
1994 Transcriptional activation by CTF proteins is mediated by a bipartite low-proline domain. Proceedings of the National Academy of Sciences of the United States of America 43 8171010
1999 The interaction between the forkhead thyroid transcription factor TTF-2 and the constitutive factor CTF/NF-1 is required for efficient hormonal regulation of the thyroperoxidase gene transcription. The Journal of biological chemistry 42 10329730
1997 DNA binding and transcriptional activation by the Ski oncoprotein mediated by interaction with NFI. Nucleic acids research 42 9380514
2020 METTL3-Mediated m6 A mRNA Methylation Modulates Tooth Root Formation by Affecting NFIC Translation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 40 32936965
2016 GPR56/ADGRG1 Activation Promotes Melanoma Cell Migration via NTF Dissociation and CTF-Mediated Gα12/13/RhoA Signaling. The Journal of investigative dermatology 40 27818281
2003 The Nuclear Factor I (NFI) gene family in mammary gland development and function. Journal of mammary gland biology and neoplasia 40 14635798
2022 Accumulation of APP-CTF induces mitophagy dysfunction in the iNSCs model of Alzheimer's disease. Cell death discovery 38 35013145
1995 Regulation of the DNA-binding and transcriptional activities of Xenopus laevis NFI-X by a novel C-terminal domain. Molecular and cellular biology 37 7565707
2022 Dual function NFI factors control fetal hemoglobin silencing in adult erythroid cells. Nature genetics 36 35618846
2014 The convergence of endosomal and autophagosomal pathways: implications for APP-CTF degradation. Autophagy 36 24447917
2014 Nuclear factor I-C (NFIC) regulates dentin sialophosphoprotein (DSPP) and E-cadherin via control of Krüppel-like factor 4 (KLF4) during dentinogenesis. The Journal of biological chemistry 36 25138274
1993 The adenovirus DNA binding protein effects the kinetics of DNA replication by a mechanism distinct from NFI or Oct-1. Nucleic acids research 36 8441675
1992 Nuclear factor I (NF I) binds to an NF I-type site but not to the CCAAT site in the human alpha-globin gene promoter. The Journal of biological chemistry 36 1569098
2024 Robust reprogramming of glia into neurons by inhibition of Notch signaling and nuclear factor I (NFI) factors in adult mammalian retina. Science advances 35 38996013
2014 Regulatory interplay between NFIC and TGF-β1 in apical papilla-derived stem cells. Journal of dental research 35 24570148
1995 NFI/X proteins: a class of NFI family of transcription factors with positive and negative regulatory domains. Cellular & molecular biology research 33 8581067
1991 DNA replication of human polyomavirus JC is stimulated by NF-I in vivo. Virology 33 1850908
1997 nfi, the gene for endonuclease V in Escherichia coli K-12. Journal of bacteriology 32 8990280
2002 Transcription factor NFIC undergoes N-glycosylation during early mammary gland involution. The Journal of biological chemistry 31 11991954
2011 Stimulation of BK virus DNA replication by NFI family transcription factors. Journal of virology 30 22205750
2021 MCPIP1-mediated NFIC alternative splicing inhibits proliferation of triple-negative breast cancer via cyclin D1-Rb-E2F1 axis. Cell death & disease 29 33824311
2020 LBX2-AS1 up-regulated by NFIC boosts cell proliferation, migration and invasion in gastric cancer through targeting miR-491-5p/ZNF703. Cancer cell international 29 32351330
2020 ECRG4 Represses Cell Proliferation and Invasiveness via NFIC/OGN/NF-κB Signaling Pathway in Bladder Cancer. Frontiers in genetics 29 32922434
2010 Evolutionarily conserved, growth plate zone-specific regulation of the matrilin-1 promoter: L-Sox5/Sox6 and Nfi factors bound near TATA finely tune activation by Sox9. Molecular and cellular biology 29 21173167
2008 Differential binding of the transcription factors Sp1, AP-1, and NFI to the promoter of the human alpha5 integrin gene dictates its transcriptional activity. Investigative ophthalmology & visual science 28 18775869
1988 Isolation and characterization of the porcine nuclear factor I (NFI) gene. FEBS letters 28 2841167
2011 CTF/NF1 transcription factors act as potent genetic insulators for integrating gene transfer vectors. Gene therapy 27 21562592
1989 Hydroxyl radical footprints reveal novel structural features around the NF I binding site in adenovirus DNA. Nucleic acids research 27 2552414
2009 Disruption of Nfic causes dissociation of odontoblasts by interfering with the formation of intercellular junctions and aberrant odontoblast differentiation. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 26 19153194
2011 A fast algorithm for computing and correcting the CTF for tilted, thick specimens in TEM. Ultramicroscopy 25 21740865
2009 Cardiac and vascular functions of the zebrafish orthologues of the type I neurofibromatosis gene NFI. Proceedings of the National Academy of Sciences of the United States of America 25 19966217
2004 Chromatin-mediated restriction of nuclear factor 1/CTF binding in a repressed and hormone-activated promoter in vivo. Molecular and cellular biology 24 15024090
1996 CTF5--a new transcriptional activator of the NFI/CTF family. Nucleic acids research 24 8710515
2023 Adipose-derived stem cell exosome NFIC improves diabetic foot ulcers by regulating miR-204-3p/HIPK2. Journal of orthopaedic surgery and research 23 37710299
2004 NFI and Oct-1 bend the Ad5 origin in the same direction leading to optimal DNA replication. Nucleic acids research 23 15576348
1999 Negative regulation of the androgen receptor gene promoter by NFI and an adjacently located multiprotein-binding site. Molecular endocrinology (Baltimore, Md.) 23 10478840
1993 Identification of a large bent DNA domain and binding sites for serum response factor adjacent to the NFI repeat cluster and enhancer region in the major IE94 promoter from simian cytomegalovirus. Journal of virology 23 8380090
2024 rs822336 binding to C/EBPβ and NFIC modulates induction of PD-L1 expression and predicts anti-PD-1/PD-L1 therapy in advanced NSCLC. Molecular cancer 22 38528526
2017 Myeloid Cell-Specific Knockout of NFI-A Improves Sepsis Survival. Infection and immunity 22 28167668
2015 Nfic regulates tooth root patterning and growth. Anatomy & cell biology 22 26417478
2010 Repressors NFI and NFY participate in organ-specific regulation of von Willebrand factor promoter activity in transgenic mice. Arteriosclerosis, thrombosis, and vascular biology 21 20431063
1996 Altered expression of the developmentally regulated NFI gene family during phorbol ester-induced differentiation of human leukemic cells. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 21 9052991
2015 NFI-A disrupts myeloid cell differentiation and maturation in septic mice. Journal of leukocyte biology 20 26259914
2012 Zinc balance is critical for NFI-C mediated regulation of odontoblast differentiation. Journal of cellular biochemistry 20 22228435
1991 Enhancement of DNA replication by transcription factors NFI and NFIII/Oct-1 depends critically on the positions of their binding sites in the adenovirus origin of replication. Biochimica et biophysica acta 20 1883843
2006 In vivo and in vitro analysis of factor binding sites in Jaagsiekte sheep retrovirus long terminal repeat enhancer sequences: roles of HNF-3, NF-I, and C/EBP for activity in lung epithelial cells. Journal of virology 19 16352558
2004 Transcriptional regulation of rat CYP2A3 by nuclear factor 1: identification of a novel NFI-A isoform, and evidence for tissue-selective interaction of NFI with the CYP2A3 promoter in vivo. The Journal of biological chemistry 19 15123731
2000 The repression of nuclear factor I/CCAAT transcription factor (NFI/CTF) transactivating domain by oxidative stress is mediated by a critical cysteine (Cys-427). The Biochemical journal 19 10794737
1997 Synergistic transactivation of HNF-1alpha, HNF-3, and NF-I contributes to the activation of the liver-specific protein C gene. DNA and cell biology 19 9174162
2016 Reciprocal autoregulation by NFI occupancy and ETV1 promotes the developmental expression of dendrite-synapse genes in cerebellar granule neurons. Molecular biology of the cell 18 26941328
1999 Sp1 and CTF/NF-1 transcription factors are involved in the basal expression of the Hmgi-c proximal promoter. Biochemical and biophysical research communications 18 10558886

Missed literature

Know a paper Affinage missed for NFIC? Flag it for the maintainers and the community.

No submissions yet.