Affinage

NFIB

Nuclear factor 1 B-type · UniProt O00712

Length
420 aa
Mass
47.4 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NFIB is a site-specific transcription factor of the NFI family that binds the TGGCA/NFI motif in vivo and controls cell-fate decisions during development and oncogenesis by reprogramming chromatin accessibility and gene transcription (PMID:2339052, PMID:24661679, PMID:27374332). Mechanistically, NFIB functions as a pioneer-type factor: it physically associates with the pre-replication complex, binds and opens nucleosomes, promotes nucleosome eviction on parental chromatin, and is necessary and sufficient to open distal regulatory elements, linking its DNA-binding activity to both replication-origin licensing and metastatic enhancer programs (PMID:37604829, PMID:27374332). Its transcriptional output is bidirectional and context-dependent: it represses targets such as Ezh2, CDKN1A/p21, and Edn2 (PMID:24553933, PMID:30350349, PMID:23389444) and activates targets such as Nfix, ITGA6, ERO1A, NDUFA4L2, PINK1, and RIP2 (PMID:29106906, PMID:31754405, PMID:33751828, PMID:36369883, PMID:33981484, PMID:35409172), operating combinatorially at composite elements co-occupied with STAT5, the androgen receptor/FOXA1, and the glucocorticoid receptor (PMID:24678731, PMID:26677878, PMID:24661679). NFIB activity is potentiated by CARM1-mediated methylation read by the effector TRIM29, which maintains open chromatin and drives SCLC onset (PMID:36690626), and is post-translationally tuned by m6A/YTHDF2-dependent mRNA stabilization and TRIM8-mediated protein-stability control (PMID:38536119). Developmentally, NFIB is required in a gene-dosage-sensitive manner for late fetal lung maturation, forebrain and corpus-callosum formation, precerebellar pontine development, and gliogenesis (PMID:15632069, PMID:19961580, PMID:19107796), and human haploinsufficiency causes intellectual disability with macrocephaly (PMID:30388402).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1990 Medium

    Established that NFIB is a distinct member of a multigene NFI family of site-specific transcription factors sharing TGGCA-binding specificity, framing the question of how functional diversity arises among near-identical DNA binders.

    Evidence Peptide microsequencing and cDNA cloning with cross-species sequence alignment

    PMID:2339052

    Open questions at the time
    • No direct functional reconstitution of NFIB DNA binding
    • Does not explain target selectivity distinguishing NFIB from paralogs
  2. 1997 High

    Showed that alternative RNA processing generates a truncated NFI-B3 isoform that heterodimerizes with other NFI members to act as a dominant-negative repressor, revealing that NFI output is tuned by isoform-driven heterodimerization.

    Evidence Alternative RNA processing characterization, reporter assays in SL-2 cells, and EMSA of heterodimer DNA binding

    PMID:9099724

    Open questions at the time
    • Endogenous abundance and physiological role of NFI-B3 not established
    • Does not address full-length NFIB target gene control
  3. 2002 Medium

    Demonstrated an in vivo developmental requirement: NFIB is needed for late lung maturation, with mutants failing to down-regulate TGF-β1 and Shh, implicating NFIB as a repressive gate on these signals.

    Evidence Nfib knockout mouse with histology and in situ expression analysis

    PMID:11850179

    Open questions at the time
    • Direct vs indirect repression of TGF-β1/Shh not resolved
    • No genome-wide binding data in this study
  4. 2005 High

    Defined the multi-organ, dosage-sensitive developmental role of NFIB across lung and forebrain, establishing haploinsufficiency as a physiologically relevant mode of action.

    Evidence Nfib knockout mouse with histology, immunohistochemistry, neuroanatomical analysis of homozygous and heterozygous animals

    PMID:15632069

    Open questions at the time
    • Molecular targets underlying each organ phenotype not identified here
    • Cell-autonomy not dissected
  5. 2009 High

    Resolved cellular mechanisms of NFIB-dependent brain development, showing non-cell-autonomous control of midline glial differentiation and pontine neuron production, and establishing functional specificity of NFIB relative to NFIA/NFIX.

    Evidence Nfib, Nfia, Nfix knockout mice with retrograde tracing, IHC, proliferation/apoptosis and migration analyses

    PMID:19107796 PMID:19961580

    Open questions at the time
    • Direct transcriptional targets driving glial/neuronal phenotypes not defined
    • Basis of NFIB-specific function among paralogs unexplained
  6. 2013 High

    Provided the first direct genomic target via ChIP-seq, showing NFIB represses Edn2 in hair follicle stem cells to restrain melanocyte stem cell differentiation, with pharmacological rescue confirming the pathway.

    Evidence HFSC-specific conditional KO, ChIP-seq, transcriptional profiling, and endothelin/KIT pharmacological rescue

    PMID:23389444

    Open questions at the time
    • Cofactors mediating Edn2 repression not identified
    • Generalizability of repression mode to other tissues not tested
  7. 2014 High

    Defined NFIB's combinatorial chromatin logic by mapping in vivo motif binding, activator-biased promoter occupancy with the glucocorticoid receptor, and direct co-occupancy with STAT5 at mammary enhancers, plus direct repression of Ezh2 in cortex.

    Evidence ChIP-seq for NFIB/STAT5 in mammary tissue, NFIB lung ChIP-seq with Nr3c1 integration, and ChIP plus reporter assays for Ezh2 in KO mice

    PMID:24553933 PMID:24661679 PMID:24678731

    Open questions at the time
    • Determinants of activator vs repressor outcome at a given site unclear
    • Direct physical contact with GR not demonstrated
  8. 2015 Medium

    Extended NFIB co-regulation to AR/FOXA1 networks and to viral transcription, positioning NFIB as a context-dependent modulator of androgen signaling and a repressor at the HIV-1 LTR.

    Evidence ChIP-seq in LNCaP, NFIB knockdown, prostate KO engraftment; and ChIP plus knockdown at the HIV-1 LTR in T-cell lines

    PMID:25664610 PMID:26677878

    Open questions at the time
    • Mechanism of AR co-occupancy (direct binding vs tethering) not resolved
    • HIV-1 LTR repression mechanism not detailed
  9. 2016 High

    Established NFIB as a chromatin-accessibility driver in SCLC metastasis, showing copy-number amplification opens distal elements and that NFIB is necessary and sufficient to increase accessibility and pro-metastatic neuronal programs.

    Evidence SCLC GEMMs with ATAC-seq, genome-wide binding analysis, and gain/loss-of-function in cell lines

    PMID:27373156 PMID:27374332

    Open questions at the time
    • Biophysical basis of NFIB-driven accessibility not yet shown
    • Cofactors required for pro-metastatic program incompletely defined
  10. 2016 Medium

    Placed NFIB in post-transcriptional lineage-restriction circuits and revealed tissue-dependent tumor-suppressive output, broadening its functional repertoire beyond a single activity.

    Evidence Conditional Drosha deletion with NFIB knockdown rescue in adult NSCs; ectopic NFIB in patient-derived GBM cells with phospho-STAT3 readout

    PMID:27083054 PMID:27545503

    Open questions at the time
    • How NFIB toggles between oncogenic and tumor-suppressive roles unresolved
    • Direct NFIB targets in GBM/STAT3 axis not mapped
  11. 2017 Medium

    Built the NFI auto-regulatory and protein-interaction architecture, showing NFIB activates Nfix, heterodimerizes additively with NFIA in cortex, and represses ESR1 transactivation in complex with YBX1/FOXA1; in melanoma NFIB drives invasion via an EZH2→MITF axis.

    Evidence Nfia/Nfib KO mice with Nfix promoter reporters, compound KO and co-IP, ESR1/FOXA1 co-IP with reporter assays, and melanoma knockdown/overexpression invasion assays

    PMID:28119061 PMID:29106906 PMID:29180470 PMID:32166136

    Open questions at the time
    • Stoichiometry and DNA-binding consequences of NFIA/NFIB heterodimers in vivo unclear
    • Whether ESR1 repression requires NFIB DNA binding not established
  12. 2018 High

    Confirmed disease causation and direct cell-cycle control, linking human NFIB haploinsufficiency to intellectual disability with macrocephaly and demonstrating direct repression of CDKN1A/p21 governing apoptosis and chemosensitivity.

    Evidence Human variant cohort with reporter assays and cortex-specific KO mouse MRI; ChIP at CDKN1A with siRNA and double-knockdown epistasis plus drug-sensitivity assays

    PMID:30350349 PMID:30388402

    Open questions at the time
    • Full target set explaining macrocephaly not enumerated
    • Context dictating p21 repression vs activation unknown
  13. 2019 Medium

    Expanded the direct-activator target catalog into cancer metastasis programs by identifying ITGA6 as a directly bound NFIB target mediating colorectal metastasis.

    Evidence ChIP, luciferase reporter, and NFIB knockdown functional assays in CRC cells

    PMID:31754405

    Open questions at the time
    • Cofactors at the ITGA6 promoter not identified
    • In vivo requirement not tested in this study
  14. 2020 Medium

    Revealed how NFIB is co-opted oncogenically through enhancer hijacking and identified KDM4D/MLL1 as a chromatin-modifying interaction module enabling NFIB-dependent gene activation.

    Evidence RNA-seq/RT-PCR fusion mapping with super-enhancer analysis in pleomorphic adenoma; co-IP and ChIP of KDM4D with NFIB/MLL1 in adipogenesis with rescue

    PMID:32080306 PMID:32654217

    Open questions at the time
    • Whether NFIB recruits or follows MLL1 at native loci unresolved
    • Direct vs indirect role of NFIB protein in fusion-driven activation not separated
  15. 2021 High

    Mapped multiple direct metastasis- and stress-relevant targets (ERO1A, PINK1, CDH1/VIM, RIP2) and uncovered RNA-level (m6A/YTHDF2) and protein-level (TRIM8) regulation of NFIB itself, plus a sufficiency for astrocyte differentiation requiring MAPK.

    Evidence In vivo piggyBac NFIB overexpression with ERO1A promoter assays; ChIP at CDH1/VIM with m6A-seq, YTHDF2 RIP and TRIM8 co-IP; PINK1 and RIP2 ChIP/reporter assays; NFIB overexpression in hPSC-NPCs with MAPK inhibition

    PMID:33751828 PMID:33949692 PMID:33981484 PMID:35409172 PMID:38536119

    Open questions at the time
    • Site of CARM1 methylation relative to these regulatory layers not yet connected here
    • Tissue specificity of each target circuit not cross-validated
  16. 2022 Medium

    Connected NFIB to drug metabolism and therapy resistance, showing repression of CYP2D6 (with a pharmacogenomic variant correlate) and activation of NDUFA4L2 to limit ROS and confer sorafenib resistance.

    Evidence NFIB overexpression in Huh7/liver spheroids with patient genotyping; ChIP at NDUFA4L2 with ROS measurement and in vivo tumor assay

    PMID:35253216 PMID:36369883

    Open questions at the time
    • Cofactors switching NFIB between CYP2D6 repression and NDUFA4L2 activation unknown
    • Direct binding at CYP2D6 not shown in this study
  17. 2023 High

    Provided mechanistic, biophysical understanding: NFIB is a pioneer factor that opens nucleosomes and partners with the pre-RC to license replication origins, and its chromatin-opening oncogenic activity is gated by CARM1 methylation read by TRIM29.

    Evidence Co-IP with pre-RC, ATAC-seq, nucleosome binding assays, single-molecule magnetic tweezers, TEM and Hi-C; plus CARM1 methylation/TRIM29 pulldown with SCLC GEMM and ATAC-seq, and a NAD+/NAMPT metabolic axis in CRC

    PMID:36690626 PMID:37491379 PMID:37604829

    Open questions at the time
    • How replication-licensing role integrates with transcriptional targeting unresolved
    • Structure of NFIB-nucleosome and NFIB-pre-RC complexes undetermined
  18. 2024 High

    Refined the oncogenic model by genetic dissection, showing NFIB contributes to but is dispensable for SCLC metastasis, with FOXA1/2 as candidate compensatory drivers, underscoring tumor plasticity.

    Evidence Conditional Nfib knockout in SCLC GEMM with molecular profiling

    PMID:37963187

    Open questions at the time
    • Mechanism of FOXA1/2 compensation not defined
    • Reconciliation with earlier necessity/sufficiency claims incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single TGGCA-binding factor selects activating versus repressing outcomes at different loci and how its pioneer/replication-licensing function is mechanistically coupled to context-specific transcriptional programs.
  • No structural model of NFIB on nucleosomes or with the pre-RC
  • Rules governing cofactor selection (STAT5 vs AR/FOXA1 vs GR vs MLL1) not defined
  • Determinants of activator vs repressor behavior at a given promoter unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-4839726 Chromatin organization 3 R-HSA-69306 DNA Replication 1
Partners
ARCARM1ESR1FOXA1KDM4DSTAT5TRIM29YBX1
Complex memberships
MLL1 complex (associated)pre-replication complex (associated)

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 NFI-B3, a truncated isoform of NFIB generated by failure to excise the first intron and use of an intron-internal polyadenylation signal, lacks independent DNA-binding and transcriptional activity but forms heterodimers with other NFI family members (NFI-B, -C, -X), reducing their DNA-binding activity and thereby repressing their transcriptional activation in a dominant-negative manner. Alternative RNA processing characterization, SL-2 cell transfection reporter assays, gel-shift (EMSA) analysis of heterodimer DNA binding The Journal of Biological Chemistry High 9099724
1990 NFIB (NFI-B) is one of at least three independent NFI gene family members encoding site-specific transcription factors with identical DNA-binding specificity (TGGCA motif); functional diversity is generated through differential RNA splicing from each gene. Peptide microsequencing, PCR-supported cDNA cloning, sequence alignment across species Nucleic Acids Research Medium 2339052
2005 Nfib is essential for late fetal lung maturation and forebrain development; Nfib-deficient mice die perinatally with severe lung hypoplasia, agenesis of the corpus callosum, basilar pons formation defects, and hippocampal developmental defects. Heterozygous animals exhibit haploinsufficiency (callosal agenesis and delayed lung maturation), indicating a gene dosage requirement. Nfib knockout mouse model; histology, immunohistochemistry, neuroanatomical analysis Molecular and Cellular Biology High 15632069
2002 Nfib null mutants display severe lung hypoplasia and die early postnatally; TGF-β1 and Sonic hedgehog (Shh) expression are not down-regulated in mutant lung epithelium at late morphogenesis stages, suggesting NFIB normally represses these signals to permit lung maturation. Nfib knockout mouse model; histology, in situ hybridization / expression analysis of TGF-β1 and Shh Mechanisms of Development Medium 11850179
2009 In Nfib-deficient mice, corpus callosum agenesis arises through non-cell-autonomous mechanisms: midline radial progenitors fail to differentiate into mature glia (without abnormal proliferation or apoptosis), and cingulate neurons show reduced neuropilin-1 expression causing failure of pioneer axons to cross the midline. Nfib knockout mouse; retrograde tracer labeling, immunohistochemistry, cell proliferation and apoptosis assays Neural Development High 19961580
2009 NFI-B expression is specifically restricted to mossy fiber populations of the precerebellar system; in Nfib(-/-) mice, basilar pontine nuclei development is delayed with fewer pontine neurons produced and slower migration, while Nfia and Nfix null mice show no pontine phenotype—demonstrating functional specificity of NFIB among NFI family members. Immunohistochemistry in Nfib, Nfia, and Nfix knockout mice; neuronal migration analysis The Journal of Comparative Neurology High 19107796
2013 NFIB in hair follicle stem cells (HFSCs) suppresses melanocyte stem cell (McSC) proliferation and differentiation by repressing endothelin 2 (Edn2) transcription; conditional deletion of Nfib in HFSCs leads to ectopic Edn2 upregulation, which promotes McSC differentiation. KIT-ligand from dermal papilla is identified as an additional signal, and endothelin receptor antagonists or KIT-blocking antibodies prevent precocious McSC differentiation in NFIB-deficient mice. HFSC-specific Nfib conditional knockout mouse; ChIP-seq, transcriptional profiling, pharmacological rescue with endothelin receptor antagonists and KIT antibodies Nature High 23389444
2014 NFIB directly binds the Ezh2 promoter and represses Ezh2 transcription; loss of Nfib in mice results in increased EZH2 expression in the neocortex and hippocampus, increased proliferating ventricular zone progenitors expressing progenitor markers, and misregulation of downstream EZH2 epigenetic targets—demonstrating NFIB as a transcriptional repressor of Ezh2 during cortical development. Nfib knockout mouse; ChIP assay showing NFIB binding to Ezh2 promoter; NFIB overexpression reporter assay; immunohistochemistry for EZH2 and progenitor markers The Journal of Neuroscience High 24553933
2014 NFIB co-occupies genomic binding sites with STAT5 and androgen-receptor/FOXA1 at composite regulatory elements marked by enhancer histone modifications; NFIB loss combined with STAT5 loss prevents formation of functional mammary alveoli, and ChIP-seq demonstrates NFIB-STAT5 co-binding at a shared set of mammary-specific gene regulatory elements. Mammary-specific Nfib conditional knockout mouse; ChIP-seq for NFIB and STAT5; gene expression analysis; integration with published HFSC ChIP-seq datasets Molecular Endocrinology High 24678731
2015 NFIB binding sites in LNCaP prostate cancer cells overlap with 64.3% of AR and FOXA1 binding sites by ChIP-seq; NFIB knockdown increases AR expression and superinduces a subset of AR target genes; loss of Nfib in mouse prostate (rescued via renal capsule engraftment) causes prostatic hyperplasia that does not resolve after castration, identifying NFIB as a co-regulator of AR signaling. ChIP-seq in LNCaP cells; NFIB siRNA knockdown; mouse Nfib knockout tissue engraftment under renal capsule; immunohistochemistry Endocrinology High 26677878
2016 Nfib copy number amplification in SCLC metastases correlates with widespread opening of distal chromatin regulatory elements enriched for NFIB binding sites; Nfib is necessary and sufficient to increase chromatin accessibility at intergenic regions and drives pro-metastatic neuronal gene expression programs in SCLC cells. Genetically engineered mouse model of SCLC; ATAC-seq for chromatin accessibility; genome-wide NFIB binding site analysis; Nfib overexpression and knockdown in SCLC cell lines Cell High 27374332
2016 NFIB overexpression in Rb1/Trp53-deleted SCLC mouse models specifically promotes metastatic spread and expansion of an E-cadherin-negative invasive cell population, while both NFIB and MYCL overexpression accelerate tumor growth; suppression of Nfib in cell lines increases apoptosis and inhibits proliferation; transcriptional analysis shows Nfib regulates axon guidance, focal adhesion, and extracellular matrix receptor interaction genes. Rb1/p53-deficient SCLC mouse model with doxycycline-inducible Nfib overexpression; Nfib knockdown in SCLC cell lines; transcriptional profiling Cell Reports High 27373156
2016 Drosha directly targets NFIB mRNA to repress its expression independently of Dicer and microRNAs in adult hippocampal NSCs; deletion of Drosha activates NFIB expression, which in turn activates oligodendrogenesis at the expense of neurogenesis; NFIB knockdown in Drosha-deficient NSCs restores neurogenesis, placing NFIB downstream of Drosha as the key effector of lineage restriction. Conditional Drosha deletion in adult dentate gyrus NSCs; NFIB knockdown rescue experiments; Dicer-independent mechanism confirmed by genetic controls Cell Stem Cell High 27545503
2017 NFIB acts downstream of BRN2 in melanoma cells to promote invasion; NFIB upregulates EZH2, which epigenetically represses MITF, thereby driving an invasive, less-proliferative melanoma phenotype. NFIB knockdown reduces migration and invasion, and EZH2 knockdown phenocopies NFIB loss. NFIB and EZH2 knockdown/overexpression in melanoma cells; migration and invasion assays; Western blot for MITF and EZH2 EBioMedicine Medium 28119061
2017 NFIB transcriptionally activates Nfix expression in the spinal cord; in the absence of Nfia or Nfib, NFIX expression is markedly reduced, and in vitro NFIB overexpression drives Nfix promoter activity, establishing a hierarchical auto-regulatory cascade: NFIB → NFIX in spinal cord gliogenesis. Nfia and Nfib knockout mice; in vitro Nfix promoter reporter assay with NFIB overexpression; immunohistochemistry Developmental Biology Medium 29106906
2017 NFIB and YBX1 physically interact with the ESR1-FOXA1 complex and inhibit ESR1 transactivational potential; FGFR2 signaling augments these interactions and further represses ESR1 target gene expression. Co-immunoprecipitation of NFIB and YBX1 with ESR1/FOXA1; ESR1 transcriptional reporter assays; FGFR2 signaling modulation Cancer Research Medium 29180470
2017 NFIA and NFIB are co-expressed in the developing cerebral cortex, can form heterodimers in vivo (detected by co-immunoprecipitation), and function additively: compound heterozygous loss of both genes causes a cortical phenotype similar to single homozygous knockouts, while double homozygous loss causes a more severe phenotype with greater ventricular enlargement and fewer differentiated glia and neurons. Compound Nfia/Nfib knockout mouse models; co-immunoprecipitation; immunofluorescence; gene expression analysis; MRI Brain and Neuroscience Advances Medium 32166136
2018 NFIB directly binds the CDKN1A (p21) promoter in TP53-mutated TNBC cells and suppresses p21 transcription; NFIB depletion induces CDKN1A expression, cell cycle arrest, apoptosis, and enhanced docetaxel sensitivity; combined knockdown of p21 and NFIB reverses the drug-sensitization, placing NFIB's effect upstream of p21. ChIP assay showing NFIB occupancy at CDKN1A promoter; siRNA knockdown; combined NFIB/p21 knockdown rescue; cell death and drug sensitivity assays The Journal of Pathology High 30350349
2018 NFIB haploinsufficiency in humans (point mutations creating premature stop codons or single-nucleotide variants) causes intellectual disability with macrocephaly; in vitro reporter assays confirm loss of transcriptional activity of variant proteins. Cortex-specific Nfib conditional knockout mice exhibit enlarged cerebral cortex, confirming macrocephaly as a functional consequence of NFIB loss. Human genetic cohort with NFIB variants; in vitro transcriptional reporter assay for variant NFIB proteins; Nfib cortex-specific conditional KO mouse; MRI and histology American Journal of Human Genetics High 30388402
2019 NFIB promotes ITGA6 transcription in colorectal cancer cells; ChIP assay demonstrates NFIB occupancy at the ITGA6 promoter, and this transcriptional activation mediates the metastasis-promoting effect of NFIB. ChIP assay for NFIB binding to ITGA6 promoter; luciferase reporter and NFIB knockdown functional assays in CRC cells Theranostics Medium 31754405
2020 NFIB activates PLAG1 and HMGA2 in pleomorphic adenoma via promoter-swapping gene fusions (NFIB-PLAG1 and HMGA2-NFIB chimeric transcripts); super-enhancers in the NFIB locus are translocated upstream of PLAG1 or downstream of HMGA2, constituting an enhancer-hijacking mechanism. RNA-seq and RT-PCR identification of fusion transcripts; chromatin landscape analysis (super-enhancer mapping) around NFIB locus Genes, Chromosomes & Cancer Medium 32654217
2020 KDM4D histone demethylase physically interacts with NFIB and the MLL1 complex; KDM4D demethylates H3K9me3, which is required for NFIB and MLL1 to deposit H3K4me3 and activate PPARγ and C/EBPα transcription during adipogenesis. NFIB and MLL1 complex bind target promoters independently of KDM4D. Co-immunoprecipitation of KDM4D with NFIB and MLL1; ChIP for H3K9me3, H3K4me3, NFIB, and MLL1 at target promoters; rescue experiments in KDM4D-depleted cells Scientific Reports High 32080306
2021 NFIB directly increases expression of ERO1A, which enhances HIF1α-VEGFA-mediated angiogenesis and lung metastatic colonization of breast cancer; overexpression of NFIB alone (via piggyBac transposon) is sufficient to enhance primary mammary tumor growth and lung metastasis. Inducible piggyBac transposon screen; NFIB overexpression in mammary tumor model; ChIP or promoter assays for ERO1A; in vivo lung colonization assays EMBO Molecular Medicine Medium 33751828
2022 NFIB regulates CYP2D6 gene expression in the liver; NFIB inhibits CYP2D6 transcription in Huh7 cells and 3D liver spheroids; carriers of NFIB rs28379954 T>C allele have reduced nuclear NFIB expression and elevated CYP2D6-dependent risperidone hydroxylation in vivo. NFIB overexpression in Huh7 cells and 3D liver spheroids; genotyping of 604 risperidone-treated patients for CYP2D6 and NFIB; translational pharmacogenomic study Clinical Pharmacology and Therapeutics Medium 35253216
2022 NFIB directly binds the NDUFA4L2 promoter and promotes its transcription, thereby reducing sorafenib-induced reactive oxygen species accumulation and promoting sorafenib resistance in hepatocellular carcinoma. ChIP assay confirming NFIB binding to NDUFA4L2 promoter; gene expression profiling; NFIB knockdown with ROS measurement; in vivo tumor growth assay Cancer Science Medium 36369883
2023 CARM1 methylates NFIB and acts as its coactivator; TRIM29 is an effector molecule that reads methylated NFIB. Both CARM1 and the CARM1 methylation site on NFIB are required for rapid SCLC onset in a mouse model, and CARM1/methylated-NFIB maintain open chromatin states in tumors. Biochemical substrate identification of NFIB as CARM1 substrate; TRIM29 pulldown as effector of methylated NFIB; SCLC mouse model with CARM1 KO and NFIB methylation-site mutant; ATAC-seq for chromatin accessibility Nature Communications High 36690626
2023 NFIB physically associates with the pre-replication complex (pre-RC) in mammalian cells, increases chromatin accessibility at replication origins by binding and opening nucleosomes (shown by nucleosome binding assay and single-molecule magnetic tweezers), and promotes nucleosome eviction on parental chromatin (TEM). NFIB deficiency alters chromosome contacts/compartments in G1 and S phase and impairs firing of a subset of early-replication origins. Cancer-associated NFIB overexpression provokes gene duplication and genomic alterations. Co-immunoprecipitation of NFIB with pre-RC components; ATAC-seq; nucleosome binding assay; single-molecule magnetic tweezers; transmission electron microscopy; Hi-C for chromosome contacts Nature Communications High 37604829
2021 NFIB directly binds to gene promoters of CDH1 (E-cadherin) and VIM (vimentin) and regulates their transcription independently of canonical EMT transcription factors; elevated m6A modification of NFIB mRNA in AR-negative CRPC recruits YTHDF2 to increase NFIB mRNA stability, while reduced TRIM8 (due to m6A modification of its own mRNA) further stabilizes NFIB protein, collectively promoting EMT and metastasis. ChIP assay for NFIB binding to CDH1 and VIM promoters; m6A-seq and YTHDF2 RIP; TRIM8 co-immunoprecipitation; NFIB knockdown migration assays; in vivo metastasis model Cancer Research High 38536119
2015 HIV-1 infection induces NFIB expression, and NFIB associates with the HIV-1 LTR region (−386 to −453 nt) as shown by ChIP assay; this association negatively correlates with HIV-1 transcription, and NFIB knockdown increases HIV-1 replication, indicating NFIB functions as a repressor of HIV-1 transcription. ChIP assay for NFIB binding to HIV-1 LTR; NFIB knockdown in T-cell lines (J1.1, J-Lat-Tat-GFP); viral replication quantification Viruses Medium 25664610
2021 Overexpression of NFIB in human pluripotent stem cell-derived neural precursor cells is sufficient to rapidly induce astrocyte differentiation in 2 weeks; MAPK pathway activity is necessary for this NFIB-driven astrogliogenesis. NFIB overexpression in hPSC-derived NPCs; RNA-seq transcriptomics; MAPK pathway inhibitor experiments; functional astrocyte assays Journal of Cellular Physiology Medium 33949692
2023 NFIB promotes colorectal cancer cell proliferation by inhibiting miR-182-5p, which normally targets and suppresses NAMPT (the NAD+ salvage synthesis rate-limiting enzyme); thus NFIB maintains NAD+ levels to sustain proliferation, and NMN supplementation rescues proliferation in NFIB-knockdown cells. NFIB knockdown with NAD+ measurement; miR-182-5p reporter assays; NMN rescue experiment; in vivo tumor growth assay Communications Biology Medium 37491379
2021 NFIB directly binds to the PINK1 promoter and regulates PINK1 transcription in kidney renal clear cell carcinoma (KIRC), promoting tumor progression and metastasis; ChIP experiments confirm NFIB occupancy at the PINK1 promoter. ChIP assay for NFIB binding to PINK1 promoter; NFIB knockdown proliferation and migration assays; in vivo tumor progression experiments PeerJ Medium 33981484
2021 NFIB transcriptionally activates RIP2 gene expression by binding to its core promoter region (−2300 to −1839 bp), as confirmed by dual-luciferase reporter assay and ChIP-PCR; NFIB overexpression exacerbates APEC-induced apoptosis and inflammation via RIP2-mediated NF-κB signaling. Dual-luciferase reporter assay; ChIP-PCR for NFIB binding to RIP2 promoter; NFIB overexpression and RIP2 knockdown in chicken HD11 cells International Journal of Molecular Sciences Medium 35409172
2014 ChIP-seq of NFIB in mouse lung at E16.5 confirms that NFIB binds in vivo to the same NFI motif identified in vitro; NFIB binding is over-represented in promoters of genes under-expressed in Nfib-KO mice, indicating an activator role; NFIB and glucocorticoid receptor (Nr3c1) co-regulate an overlapping set of 52 genes (~13x greater than chance) during lung maturation. ChIP-seq for NFIB in mouse lung; motif analysis; integration with Nr3c1-KO microarray data BMC Genomics Medium 24661679
2016 NFIB expression in patient-derived GBM cells (classical and mesenchymal subtypes) activates phospho-STAT3 signaling; ectopic NFIB expression inhibits tumourigenesis in these subtypes, identifying context-dependent tumor suppressor activity mediated through STAT3 pathway activation. Ectopic NFIB expression in patient-derived GBM cells; tumourigenesis assays; Western blot for phospho-STAT3 Oncotarget Medium 27083054
2024 Conditional genetic knockout of Nfib in SCLC genetically engineered mouse models demonstrates that while Nfib upregulation contributes to tumor progression, Nfib is not required for metastasis; FOXA1/2 are identified as candidate drivers of Nfib-independent metastatic progression, highlighting SCLC plasticity. Conditional Nfib knockout in SCLC GEMM; molecular profiling identifying FOXA1/2 upregulation in NFIB-KO tumors Cancer Research High 37963187

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proceedings of the National Academy of Sciences of the United States of America 626 19841262
2016 Nfib Promotes Metastasis through a Widespread Increase in Chromatin Accessibility. Cell 303 27374332
2011 Analysis of MYB expression and MYB-NFIB gene fusions in adenoid cystic carcinoma and other salivary neoplasms. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 276 21572406
2005 The transcription factor gene Nfib is essential for both lung maturation and brain development. Molecular and cellular biology 253 15632069
2010 Comprehensive analysis of the MYB-NFIB gene fusion in salivary adenoid cystic carcinoma: Incidence, variability, and clinicopathologic significance. Clinical cancer research : an official journal of the American Association for Cancer Research 239 20702610
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
2015 Novel MYBL1 Gene Rearrangements with Recurrent MYBL1-NFIB Fusions in Salivary Adenoid Cystic Carcinomas Lacking t(6;9) Translocations. Clinical cancer research : an official journal of the American Association for Cancer Research 170 26631609
2013 NFIB is a governor of epithelial-melanocyte stem cell behaviour in a shared niche. Nature 141 23389444
2012 Clinically significant copy number alterations and complex rearrangements of MYB and NFIB in head and neck adenoid cystic carcinoma. Genes, chromosomes & cancer 125 22505352
2011 Novel chromosomal rearrangements and break points at the t(6;9) in salivary adenoid cystic carcinoma: association with MYB-NFIB chimeric fusion, MYB expression, and clinical outcome. Clinical cancer research : an official journal of the American Association for Cancer Research 125 21976542
2016 Transcription Factor NFIB Is a Driver of Small Cell Lung Cancer Progression in Mice and Marks Metastatic Disease in Patients. Cell reports 124 27373156
1998 Identification of NFIB as recurrent translocation partner gene of HMGIC in pleomorphic adenomas. Oncogene 121 9484777
2021 CircHIF1A regulated by FUS accelerates triple-negative breast cancer progression by modulating NFIB expression and translocation. Oncogene 87 33714984
2002 Nuclear factor I-B (Nfib) deficient mice have severe lung hypoplasia. Mechanisms of development 85 11850179
2015 A Genome-Wide Scan Identifies Variants in NFIB Associated with Metastasis in Patients with Osteosarcoma. Cancer discovery 84 26084801
2011 The MYB-NFIB gene fusion-a novel genetic link between adenoid cystic carcinoma and dermal cylindroma. The Journal of pathology 84 21618541
2017 MYBL1 rearrangements and MYB amplification in breast adenoid cystic carcinomas lacking the MYB-NFIB fusion gene. The Journal of pathology 79 29149504
2016 Multipotency of Adult Hippocampal NSCs In Vivo Is Restricted by Drosha/NFIB. Cell stem cell 79 27545503
2019 miR-302a Inhibits Metastasis and Cetuximab Resistance in Colorectal Cancer by Targeting NFIB and CD44. Theranostics 75 31754405
2014 MYB-NFIB gene fusion in adenoid cystic carcinoma of the breast with special focus paid to the solid variant with basaloid features. Human pathology 75 25217885
2017 NFIB Mediates BRN2 Driven Melanoma Cell Migration and Invasion Through Regulation of EZH2 and MITF. EBioMedicine 72 28119061
2014 NFIB-mediated repression of the epigenetic factor Ezh2 regulates cortical development. The Journal of neuroscience : the official journal of the Society for Neuroscience 70 24553933
2014 miR-365 promotes cutaneous squamous cell carcinoma (CSCC) through targeting nuclear factor I/B (NFIB). PloS one 67 24949940
2017 MYB, MYBL1, MYBL2 and NFIB gene alterations and MYC overexpression in salivary gland adenoid cystic carcinoma. Histopathology 66 28594149
2017 ERα Binding by Transcription Factors NFIB and YBX1 Enables FGFR2 Signaling to Modulate Estrogen Responsiveness in Breast Cancer. Cancer research 65 29180470
2016 NFIB overexpression cooperates with Rb/p53 deletion to promote small cell lung cancer. Oncotarget 62 27613844
2009 Multiple non-cell-autonomous defects underlie neocortical callosal dysgenesis in Nfib-deficient mice. Neural development 53 19961580
2011 NFIB is a potential target for estrogen receptor-negative breast cancers. Molecular oncology 52 21925980
2017 Transcriptional regulation of Nfix by NFIB drives astrocytic maturation within the developing spinal cord. Developmental biology 51 29106906
2015 p53-induced microRNA-1246 inhibits the cell growth of human hepatocellular carcinoma cells by targeting NFIB. Oncology reports 49 25591821
2012 MicroRNA profiling in pediatric pilocytic astrocytoma reveals biologically relevant targets, including PBX3, NFIB, and METAP2. Neuro-oncology 48 23161775
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
2018 NFIB Haploinsufficiency Is Associated with Intellectual Disability and Macrocephaly. American journal of human genetics 47 30388402
2021 YAP regulates alveolar epithelial cell differentiation and AGER via NFIB/KLF5/NKX2-1. iScience 46 34466790
2017 miR-1224 inhibits cell proliferation in acute liver failure by targeting the antiapoptotic gene Nfib. Journal of hepatology 43 28645739
2021 The NFIB-ERO1A axis promotes breast cancer metastatic colonization of disseminated tumour cells. EMBO molecular medicine 42 33751828
2016 Developmental transcription factor NFIB is a putative target of oncofetal miRNAs and is associated with tumour aggressiveness in lung adenocarcinoma. The Journal of pathology 42 27357447
2024 m6A Modification Promotes EMT and Metastasis of Castration-Resistant Prostate Cancer by Upregulating NFIB. Cancer research 41 38536119
2018 NFIB promotes cell survival by directly suppressing p21 transcription in TP53-mutated triple-negative breast cancer. The Journal of pathology 41 30350349
2020 Hsa_circ_0026416 promotes proliferation and migration in colorectal cancer via miR-346/NFIB axis. Cancer cell international 38 33061846
2016 Nuclear factor one B (NFIB) encodes a subtype-specific tumour suppressor in glioblastoma. Oncotarget 36 27083054
2005 Fusion of the HMGA2 and NFIB genes in lipoma. Virchows Archiv : an international journal of pathology 36 16133369
2001 A novel amplicon at 9p23 - 24 in squamous cell carcinoma of the esophagus that lies proximal to GASC1 and harbors NFIB. Japanese journal of cancer research : Gann 36 11346465
2023 The NFIB/CARM1 partnership is a driver in preclinical models of small cell lung cancer. Nature communications 34 36690626
2020 Common Regulatory Targets of NFIA, NFIX and NFIB during Postnatal Cerebellar Development. Cerebellum (London, England) 31 31838646
2008 NFIB rearrangement in superficial, retroperitoneal, and colonic lipomas with aberrations involving chromosome band 9p22. Genes, chromosomes & cancer 31 18663748
2022 The Polymorphic Nuclear Factor NFIB Regulates Hepatic CYP2D6 Expression and Influences Risperidone Metabolism in Psychiatric Patients. Clinical pharmacology and therapeutics 30 35253216
2018 UM-HACC-2A: MYB-NFIB fusion-positive human adenoid cystic carcinoma cell line. Oral oncology 28 30527239
2017 Combined allelic dosage of Nfia and Nfib regulates cortical development. Brain and neuroscience advances 27 32166136
2009 HMGA2-NFIB fusion in a pediatric intramuscular lipoma: a novel case of NFIB alteration in a large deep-seated adipocytic tumor. Cancer genetics and cytogenetics 27 19837271
2019 MicroRNA-346 inhibits the growth of glioma by directly targeting NFIB. Cancer cell international 26 31807116
2018 NFIB promotes cell growth, aggressiveness, metastasis and EMT of gastric cancer through the Akt/Stat3 signaling pathway. Oncology reports 26 30015981
2017 Frequent NFIB-associated Gene Rearrangement in Adenoid Cystic Carcinoma of the Vulva. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 24 27662035
2015 Nfib Regulates Transcriptional Networks That Control the Development of Prostatic Hyperplasia. Endocrinology 24 26677878
2009 Absence of the transcription factor Nfib delays the formation of the basilar pontine and other mossy fiber nuclei. The Journal of comparative neurology 24 19107796
2020 Regulatory effect of LncRNA DRAIC/miR-149-5p/NFIB molecular network on autophagy of esophageal cancer cells and its biological behavior. Experimental and molecular pathology 21 32659236
2020 Long non-coding RNA OIP5-AS1 plays an oncogenic role in ovarian cancer through targeting miR-324-3p/NFIB axis. European review for medical and pharmacological sciences 21 32706064
2022 Development and Characterization of MYB-NFIB Fusion Expression in Adenoid Cystic Carcinoma. Cancers 20 35565392
2022 Transcriptional regulation of NDUFA4L2 by NFIB induces sorafenib resistance by decreasing reactive oxygen species in hepatocellular carcinoma. Cancer science 20 36369883
2021 NFIB induces functional astrocytes from human pluripotent stem cell-derived neural precursor cells mimicking in vivo astrogliogenesis. Journal of cellular physiology 20 33949692
2021 lncRNA LOXL1-AS1 promotes liver cancer cell proliferation and migration by regulating the miR-377-3p/NFIB axis. Oncology letters 20 34267816
2020 Histone demethylase KDM4D cooperates with NFIB and MLL1 complex to regulate adipogenic differentiation of C3H10T1/2 mesenchymal stem cells. Scientific reports 20 32080306
2020 Activation of PLAG1 and HMGA2 by gene fusions involving the transcriptional regulator gene NFIB. Genes, chromosomes & cancer 20 32654217
2019 Transcription factors NFIA and NFIB induce cellular differentiation in high-grade astrocytoma. Journal of neuro-oncology 20 31760595
2021 CircATL2 enhances paclitaxel resistance of ovarian cancer via impacting miR-506-3p/NFIB axis. Drug development research 19 34541682
2020 MicroRNA-138-5p targets the NFIB-Snail1 axis to inhibit colorectal cancer cell migration and chemoresistance. Cancer cell international 19 33013202
2019 LncRNA LINC00461 Promotes Colorectal Cancer Progression via miRNA-323b-3p/NFIB Axis. OncoTargets and therapy 19 31908480
2017 Non-small cell lung cancer: miR-30d suppresses tumor invasion and migration by directly targeting NFIB. Biotechnology letters 19 28861760
2014 NFIB regulates embryonic development of submandibular glands. Journal of dental research 19 25403566
2011 Studies of genomic imbalances and the MYB-NFIB gene fusion in polymorphous low-grade adenocarcinoma of the head and neck. International journal of oncology 19 21901247
2022 Transcriptional Regulation of RIP2 Gene by NFIB Is Associated with Cellular Immune and Inflammatory Response to APEC Infection. International journal of molecular sciences 17 35409172
2022 Knockdown of circ-PIP5K1A overcomes resistance to cisplatin in ovarian cancer by miR-942-5p/NFIB axis. Anti-cancer drugs 17 36730637
2015 Transcription factor and microRNA interactions in lung cells: an inhibitory link between NK2 homeobox 1, miR-200c and the developmental and oncogenic factors Nfib and Myb. Respiratory research 17 25763778
2021 NFIB promotes the progression of gastric cancer by upregulating circMAP7D1 to stabilize HER2 mRNA. Molecular medicine reports 16 33576439
2020 LINC00319 promotes osteosarcoma progression by regulating the miR-455-3p/NFIB axis. The journal of gene medicine 16 32621625
2014 Coregulation of genetic programs by the transcription factors NFIB and STAT5. Molecular endocrinology (Baltimore, Md.) 16 24678731
2022 Circular RNA circPTK2 modulates migration and invasion via miR-136/NFIB signaling on triple-negative breast cancer cells in vitro. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 15 35234989
2021 NFIB-Mediated lncRNA PVT1 Aggravates Laryngeal Squamous Cell Carcinoma Progression via the miR-1301-3p/MBNL1 Axis. Journal of immunology research 14 34805417
2020 RGMB-AS1/miR-22-3p/NFIB axis contributes to the progression of gastric cancer. Neoplasma 14 32064882
2020 Inhibition of microRNA-346 inhibits myocardial inflammation and apoptosis after myocardial infarction via targeting NFIB. European review for medical and pharmacological sciences 14 33275244
2014 An overlapping set of genes is regulated by both NFIB and the glucocorticoid receptor during lung maturation. BMC genomics 14 24661679
2024 Small Cell Lung Cancer Plasticity Enables NFIB-Independent Metastasis. Cancer research 13 37963187
2021 MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting nuclear factor I/B (NFIB). Acta neuropathologica communications 13 34922631
2019 MYB-NFIB gene fusion in prostatic basal cell carcinoma: clinicopathologic correlates and comparison with basal cell adenoma and florid basal cell hyperplasia. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 13 31189999
2015 HIV-1 induced nuclear factor I-B (NF-IB) expression negatively regulates HIV-1 replication through interaction with the long terminal repeat region. Viruses 13 25664610
2023 NFIB facilitates replication licensing by acting as a genome organizer. Nature communications 12 37604829
2021 NFIA and NFIB function as tumour suppressors in high-grade glioma in mice. Carcinogenesis 12 33346791
2023 Downregulation of miR-182-5p by NFIB promotes NAD+ salvage synthesis in colorectal cancer by targeting NAMPT. Communications biology 11 37491379
2023 MiR-326-mediated overexpression of NFIB offsets TGF-β induced epithelial to mesenchymal transition and reverses lung fibrosis. Cellular and molecular life sciences : CMLS 11 37950757
2022 Circ_0007841 knockdown confers cisplatin sensitivity to ovarian cancer cells by down-regulation of NFIB expression in a miR-532-5p-dependent manner. Journal of chemotherapy (Florence, Italy) 11 35380509
2022 Circ_0082182 upregulates the NFIB level via sponging miR-326 to promote oxaliplatin resistance and malignant progression of colorectal cancer cells. Molecular and cellular biochemistry 11 36219357
2021 LncRNA PCAT1 enhances cell proliferation, migration and invasion by miR-508-3p/NFIB axis in diffuse large B-cell lymphoma. European review for medical and pharmacological sciences 11 33829443
2021 NFIB promotes the migration and progression of kidney renal clear cell carcinoma by regulating PINK1 transcription. PeerJ 11 33981484
2015 PAX6 does not regulate Nfia and Nfib expression during neocortical development. Scientific reports 11 26021864
2016 The impact of the MYB-NFIB fusion proto-oncogene in vivo. Oncotarget 10 27213588
2022 Circ_0003645 serves as miR-335-5p sponge to promote the biological process of diffuse large B-cell lymphoma by upregulating NFIB. Autoimmunity 9 35001739
2020 NFIB functions as an oncogene in estrogen receptor-positive breast cancer and is regulated by miR-205-5p. Pathology, research and practice 9 33038688
2019 MYB-NFIB gene fusions identified in archival adenoid cystic carcinoma tissue employing NanoString analysis: an exploratory study. Diagnostic pathology 9 31301736
2022 Exosomal miR-626 promotes the malignant behavior of oral cancer cells by targeting NFIB. Molecular biology reports 8 35711020
2017 Nfib hemizygous mice are protected from hyperoxic lung injury and death. Physiological reports 8 28830981

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