Affinage

NFIB

Nuclear factor 1 B-type · UniProt O00712

Length
420 aa
Mass
47.4 kDa
Annotated
2026-04-29
100 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NFIB is a nuclear factor I (NFI) family transcription factor that binds the NFI consensus motif as homodimers or heterodimers (with NFIA) to activate or repress diverse target gene promoters, thereby orchestrating lung maturation, brain development, gliogenesis, and chromatin accessibility programs (PMID:15632069, PMID:9099724, PMID:32166136). NFIB directly binds and opens nucleosomes to increase chromatin accessibility at replication origins and distal regulatory elements, facilitating replication licensing through association with the pre-replication complex and driving metastatic gene expression programs in small cell lung cancer (PMID:37604829, PMID:27374332). It directly regulates transcription of targets including Ezh2, CDKN1A/p21, Edn2, NDUFA4L2, ITGA6, PINK1, CYP2D6, and NFIX, and is itself regulated post-transcriptionally by Drosha-mediated mRNA cleavage, YTHDF2-dependent m6A stabilization, and TRIM8-mediated ubiquitination, while serving as a CARM1 methylation substrate that recruits TRIM29 for transcriptional coactivation (PMID:24553933, PMID:13889444, PMID:30350349, PMID:27545503, PMID:38536119, PMID:36690626). NFIB is recurrently hijacked as a fusion partner (MYB-NFIB, HMGA2-NFIB, PLAG1-NFIB) in adenoid cystic carcinoma and pleomorphic adenoma, where its super-enhancers drive oncogene activation through enhancer hijacking (PMID:19841262, PMID:9484777, PMID:32654217).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1997 High

    The discovery that a truncated NFIB isoform (NFI-B3) acts as a dominant-negative by heterodimerizing with full-length NFI proteins established that NFIB functions through dimerization-dependent DNA binding and that alternative splicing generates regulatory diversity within the NFI family.

    Evidence Reconstitution in NFI-null Drosophila SL-2 cells with EMSA and transcription assays

    PMID:9099724

    Open questions at the time
    • Crystal structure of NFIB homodimer/heterodimer not determined
    • In vivo relevance of NFI-B3 dominant-negative isoform not tested
  2. 1998 High

    Identification of HMGA2-NFIB fusion transcripts in pleomorphic adenomas revealed that the NFIB locus is a recurrent translocation target in salivary gland tumors, later extended to MYB-NFIB in adenoid cystic carcinoma and PLAG1-NFIB fusions.

    Evidence 3'-RACE and RT-PCR in two independent pleomorphic adenoma cases; MYB-NFIB fusion characterized by RT-PCR and sequencing in ACC

    PMID:19841262 PMID:32654217 PMID:9484777

    Open questions at the time
    • Direct functional consequence of NFIB sequences in chimeric proteins not fully resolved
    • Enhancer-hijacking mechanism for NFIB super-enhancers inferred but not functionally validated by deletion
  3. 2002 High

    Nfib knockout mice dying perinatally with severe lung hypoplasia and failure to downregulate TGF-β1/Shh established NFIB as essential for late fetal lung maturation, answering whether any single NFI family member is non-redundant in organogenesis.

    Evidence Nfib-null mouse with histology, immunostaining, and in situ hybridization

    PMID:11850179

    Open questions at the time
    • Direct transcriptional targets mediating lung saccularization were not identified in this study
    • Whether NFIB represses TGF-β1/Shh directly or indirectly was unresolved
  4. 2005 High

    Expanded phenotyping of Nfib-null mice revealed callosal agenesis, hippocampal defects, and basilar pons malformation — more severe than Nfia loss — establishing NFIB as the predominant NFI member in forebrain and hindbrain development.

    Evidence Nfib knockout with histological and anatomical analysis; Nfib-specific pontine phenotype confirmed by comparison with Nfia/Nfix nulls

    PMID:15632069 PMID:19107796 PMID:19961580

    Open questions at the time
    • Cell-autonomous vs. non-cell-autonomous contributions initially unclear (partially resolved for corpus callosum by PMID:19961580)
    • Downstream transcriptional targets in brain not yet identified
  5. 2013 High

    Conditional Nfib knockout in hair follicle stem cells, combined with ChIP-seq, identified Edn2 as a direct NFIB target whose ectopic activation drives premature melanocyte stem cell differentiation — the first demonstration that NFIB coordinates inter-lineage stem cell niche signaling.

    Evidence Conditional KO mouse, ChIP-seq, pharmacological rescue with endothelin receptor antagonists and KIT-blocking antibodies

    PMID:23389444

    Open questions at the time
    • Whether NFIB directly represses or indirectly controls Edn2 chromatin state not fully dissected
    • Relevance to human hair graying not demonstrated
  6. 2014 High

    ChIP and reporter assays showed NFIB directly binds and represses the Ezh2 promoter, limiting neural progenitor self-renewal; genome-wide ChIP-seq in fetal lung confirmed NFIB recognizes the NFI consensus motif in vivo and co-regulates genes with the glucocorticoid receptor, defining NFIB's dual role as a direct activator and repressor.

    Evidence ChIP/ChIP-seq in brain and lung, Nfib-KO microarray, overexpression reporter assays

    PMID:24553933 PMID:24661679

    Open questions at the time
    • Genome-wide activator vs. repressor target classification incomplete
    • Mechanism of context-dependent switching between activation and repression unknown
  7. 2014 High

    ChIP-seq in mammary epithelium revealed NFIB co-occupies enhancers with STAT5, and combined Nfib/Stat5 loss prevents alveolar function, establishing NFIB as a tissue-specific cofactor that collaborates with lineage-determining transcription factors at enhancers.

    Evidence Mammary conditional Nfib KO, ChIP-seq for NFIB and STAT5, gene expression analysis

    PMID:24678731

    Open questions at the time
    • Whether NFIB directly interacts with STAT5 protein was not shown by co-IP in this study
    • Mechanism of enhancer selection by NFIB-STAT5 unknown
  8. 2015 High

    ChIP-seq in prostate cancer cells demonstrated extensive NFIB co-binding with AR and FOXA1 at regulatory elements, and Nfib loss caused castration-resistant prostatic hyperplasia, revealing NFIB as a coregulator that restrains androgen receptor signaling.

    Evidence ChIP-seq in LNCaP cells, siRNA knockdown, Nfib-KO prostatic engraftment in vivo

    PMID:26677878

    Open questions at the time
    • Direct physical interaction between NFIB and AR not shown by co-IP
    • Mechanism by which NFIB restrains AR target gene expression unresolved
  9. 2016 High

    Three independent studies in SCLC mouse models converged to show that NFIB amplification/overexpression drives metastasis by opening distal chromatin at thousands of regulatory elements genome-wide, establishing NFIB as a chromatin accessibility factor — not merely a classical transcription factor — that enables metastatic gene programs.

    Evidence ATAC-seq, NFIB KD/OE, in vivo metastasis assays in Rb1/Trp53-deleted GEMMs

    PMID:27373156 PMID:27374332 PMID:27613844

    Open questions at the time
    • Biophysical mechanism of chromatin opening not yet determined (resolved later in 2020)
    • Whether NFIB is strictly required for metastasis or can be compensated was unresolved
  10. 2016 High

    Discovery that Drosha directly destabilizes NFIB mRNA independently of Dicer/miRNAs to restrict oligodendrocyte fate in adult hippocampal stem cells established a non-canonical post-transcriptional control layer for NFIB levels during cell fate decisions.

    Evidence Conditional Drosha KO in adult NSCs, NFIB knockdown rescue, lineage tracing

    PMID:27545503

    Open questions at the time
    • Drosha cleavage site on NFIB mRNA not mapped
    • Whether this mechanism operates outside hippocampus unknown
  11. 2017 Medium

    Multiple studies expanded NFIB's transcriptional network: NFIB activates NFIX in spinal cord gliogenesis (establishing NFI family hierarchy), forms heterodimers with NFIA in vivo (co-IP), interacts with ESR1-FOXA1 to repress estrogen receptor signaling, and in melanoma acts downstream of BRN2 to upregulate EZH2.

    Evidence Compound Nfia/Nfib KO, co-IP, promoter reporter assays, KD/OE in melanoma and breast cancer cells

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

    Open questions at the time
    • Heterodimer stoichiometry and DNA-binding preference differences between NFIB homodimers and NFIA-NFIB heterodimers not characterized
    • NFIB context-dependent switch from Ezh2 repressor (brain) to EZH2 activator (melanoma) mechanistically unexplained
  12. 2018 High

    ChIP demonstrated NFIB directly occupies the CDKN1A (p21) promoter in TP53-mutant TNBC; double knockdown of p21 and NFIB rescued docetaxel sensitivity, establishing p21 as a critical downstream effector of NFIB-mediated drug resistance.

    Evidence ChIP, siRNA single and double knockdown, drug sensitivity assays in TNBC cells

    PMID:30350349

    Open questions at the time
    • Whether NFIB repression of p21 requires TP53 mutation context not tested in TP53-WT cells
    • Generalizability to other chemotherapeutic agents not established
  13. 2020 High

    Single-molecule magnetic tweezers and TEM revealed NFIB directly binds and opens nucleosomes, and co-IP showed it associates with pre-replication complex components; NFIB deficiency altered replication origin firing and 3D chromosome compartments, unifying NFIB's chromatin remodeling and replication licensing activities.

    Evidence Magnetic tweezers, TEM, co-IP with pre-RC, ChIP-seq/ATAC-seq, Hi-C in mammalian cells

    PMID:37604829

    Open questions at the time
    • Whether nucleosome opening is catalytic or stoichiometric not determined
    • Structural basis of NFIB-nucleosome interaction unknown
    • Relative contribution of replication vs. transcription functions to metastasis not separated
  14. 2023 High

    Identification of CARM1 as a methyltransferase for NFIB, with methylated NFIB recruiting TRIM29, established the first defined post-translational modification-effector axis for NFIB; in vivo, a methylation-site mutant delayed SCLC onset as severely as CARM1 loss.

    Evidence Biochemical substrate identification, co-IP, ATAC-seq, mouse SCLC model with NFIB methylation-site point mutant

    PMID:36690626

    Open questions at the time
    • TRIM29's effector mechanism at NFIB target sites not defined
    • Whether CARM1-NFIB axis operates outside SCLC unknown
  15. 2024 High

    Discovery that YTHDF2 stabilizes m6A-modified NFIB mRNA while TRIM8 ubiquitinates NFIB protein for degradation provided dual epitranscriptomic/proteasomal control of NFIB levels, and conditional Nfib KO in SCLC GEMMs revealed FOXA1/2 can compensate for NFIB loss in driving metastasis.

    Evidence m6A-RIP, YTHDF2/TRIM8 functional studies, conditional Nfib KO in SCLC GEMM with molecular profiling

    PMID:37963187 PMID:38536119

    Open questions at the time
    • Whether YTHDF2-NFIB and TRIM8-NFIB axes interact or are independent pathways not tested
    • FOXA1/2 compensation mechanism and whether it requires chromatin opening activity unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of NFIB's nucleosome-opening activity, how the same factor switches between transcriptional activation and repression in different tissues, and whether NFIB's replication licensing and transcriptional functions are mechanistically separable.
  • No high-resolution structure of NFIB bound to nucleosome or DNA
  • Context-dependent activation vs. repression mechanism unknown
  • Replication vs. transcription functions not genetically separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 7 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 5 GO:0005694 chromosome 1
Pathway
R-HSA-74160 Gene expression (Transcription) 11 R-HSA-1266738 Developmental Biology 8 R-HSA-1643685 Disease 4 R-HSA-4839726 Chromatin organization 3 R-HSA-1640170 Cell Cycle 1 R-HSA-69306 DNA Replication 1
Partners
CARM1ESR1FOXA1KDM4DNFIASTAT5TRIM29TRIM8
Complex memberships
NFI homodimer/heterodimerpre-replication complex (pre-RC)

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Nfib-deficient mice exhibit defects in lung maturation (failure of saccularization, reduced epithelial differentiation markers), callosal agenesis, forebrain defects more severe than Nfia-null, basilar pons formation defects, and hippocampal developmental abnormalities, establishing NFIB as essential for late fetal lung maturation and brain development; heterozygotes also show haploinsufficiency phenotypes. Knockout mouse model with histological, molecular, and anatomical phenotypic analysis Molecular and cellular biology High 11850179 15632069
2002 Nfib null mutants die early postnatally with severe lung hypoplasia; TGF-β1 and Shh are not downregulated in mutant lung epithelium at late morphogenesis stages, suggesting NFIB-dependent repression of these signaling molecules is required for normal lung maturation. Knockout mouse model, immunostaining, in situ hybridization Mechanisms of development High 11850179
1997 NFI-B3, a truncated isoform of NFIB generated by alternative RNA processing (retention of first intron + intron-internal polyadenylation), lacks DNA-binding activity alone but forms heterodimers with other NFI-B, -C, and -X isoforms, reducing their DNA-binding and transcriptional activation in a dominant-negative manner. In vitro transcription assay in NFI-null SL-2 cells, gel shift (EMSA), co-expression of isoforms The Journal of biological chemistry High 9099724
2009 In Nfib-deficient mice, callosal agenesis results from non-cell-autonomous defects: (1) midline radial progenitors fail to differentiate into mature glia (not due to proliferation/apoptosis changes), and (2) cingulate cortex neurons that express Nfib fail to extend neuropilin-1-positive pioneering axons across the midline, with diminished neuropilin-1 expression. Knockout mouse histology, retrograde tracer labeling, immunohistochemistry, cellular proliferation/apoptosis assays Neural development High 19961580
2009 In Nfib-null mice, development of the basilar pontine nuclei is delayed (neurons migrate 1–2 days later than controls) and fewer pontine neurons are produced; other mossy fiber nuclei of the caudal medulla also show developmental delay. Nfia and Nfix null mice show no pontine phenotype, indicating Nfib-specific action. Knockout mouse immunohistochemistry, comparative analysis of Nfia and Nfix null mice The Journal of comparative neurology High 19107796
2013 Hair-follicle-stem-cell-specific conditional knockout of Nfib in mice uncouples melanocyte stem cell synchrony from the hair cycle: loss of NFIB in hair follicle stem cells promotes premature melanocyte stem cell proliferation and differentiation via ectopic activation of the NFIB target Edn2 (endothelin 2). Endothelin receptor antagonists or KIT-blocking antibodies rescue the premature melanocyte differentiation phenotype. Conditional KO mouse, ChIP-seq, transcriptional profiling, pharmacological rescue with receptor antagonists/antibodies Nature High 23389444
2014 NFIB binds the Ezh2 promoter and represses Ezh2 transcription, thereby limiting neural progenitor cell self-renewal during cortical development; Nfib-null mice show increased EZH2 expression and excess proliferating ventricular zone progenitors, with misregulation of downstream EZH2 epigenetic targets. Knockout mouse, ChIP (NFIB binding to Ezh2 promoter), NFIB overexpression reporter assay, immunohistochemistry The Journal of neuroscience High 24553933
2016 In a mouse SCLC model, Nfib copy-number amplification correlates with widespread opening of distal chromatin regulatory elements genome-wide; Nfib is necessary and sufficient to increase chromatin accessibility at intergenic regions and drives pro-metastatic neuronal gene expression programs, promoting metastatic spread of SCLC. Genetically engineered mouse model (GEMM), ATAC-seq (chromatin accessibility), NFIB KD/OE in cancer cells, in vivo metastasis assays Cell High 27374332
2016 NFIB overexpression specifically promotes metastatic spread (not just primary tumor growth) in Rb1/Trp53-deleted mouse SCLC models; high NFIB levels are associated with poorly differentiated, E-cadherin-negative invasive tumor cell populations. Mouse SCLC model with NFIB overexpression, histological and immunophenotypic analysis Cell reports High 27373156
2016 In mouse SCLC models, Nfib overexpression cooperates with Rb1/Trp53 deletion to accelerate SCLC; Nfib suppression in cell lines increases apoptosis and reduces proliferation; Nfib transcriptionally regulates axon guidance, focal adhesion, and extracellular matrix-receptor interaction gene networks; Nfib amplifications are more frequent in liver metastases than primary tumors. Mouse SCLC model (doxycycline-inducible Nfib overexpression), cell line Nfib knockdown, transcriptional profiling Oncotarget High 27613844
2016 Drosha directly targets NFIB mRNA to repress its expression in adult hippocampal neural stem cells, independently of Dicer and microRNAs; Drosha deletion activates oligodendrogenesis and reduces neurogenesis, phenotypes that are rescued by NFIB knockdown, establishing a Drosha/NFIB axis that restricts oligodendrocyte fate acquisition. Conditional Drosha KO in adult dentate gyrus NSCs, NFIB knockdown rescue experiments, lineage tracing Cell stem cell High 27545503
2014 NFIB (together with STAT5) co-regulates mammary-specific genetic programs: ChIP-seq demonstrates STAT5 and NFIB bind composite regulatory elements with H3K4me2 enhancer marks and progesterone receptor binding; combined absence of NFIB and STAT5 prevents functional alveoli formation, whereas NFIB alone is not required for alveolar expansion. Mammary-specific conditional Nfib KO, ChIP-seq (NFIB and STAT5), gene expression analysis Molecular endocrinology High 24678731
2017 NFIB acts downstream of BRN2 in melanoma to promote migration and invasion via upregulation of the polycomb protein EZH2; NFIB-driven EZH2 upregulation leads to decreased MITF expression, shifting cells to a less proliferative, more invasive phenotype. Knockdown/overexpression in melanoma cells, migration/invasion assays, western blot, gene expression analysis EBioMedicine Medium 28119061
2017 NFIB directly interacts with the CDKN1A (p21) promoter in TP53-mutated TNBC cells to suppress p21 transcription; NFIB knockdown induces p21 upregulation, cell death, and cell cycle arrest, and double knockdown of p21 and NFIB reverses docetaxel-induced growth inhibition, establishing p21 as a key mediator of NFIB's pro-survival, drug-resistance function. ChIP (NFIB binding to CDKN1A promoter), siRNA knockdown, double knockdown rescue experiment, drug sensitivity assays The Journal of pathology High 30350349
2015 In androgen-dependent LNCaP prostate cancer cells, 64.3% of NFIB ChIP-seq binding sites overlap with AR and FOXA1 binding sites; NFIB knockdown increases AR expression and superinduces a subset of AR target genes; loss of Nfib in mouse prostate (renal capsule engraftment model) results in prostatic hyperplasia not resolved by castration, suggesting NFIB is a coregulator of AR action. ChIP-seq (NFIB in LNCaP cells), siRNA knockdown, Nfib KO prostatic renal capsule engraftment Endocrinology High 26677878
2021 NFIB directly upregulates ERO1A transcription, which enhances HIF1α-VEGFA-mediated angiogenesis to promote metastatic colonization; NFIB overexpression alone (via piggyBac transposon screen) is sufficient to enhance primary mammary tumor growth and lung metastatic colonization. PiggyBac transposon mutagenesis screen, NFIB overexpression in mammary tumor cells, in vivo metastasis assays, mechanistic follow-up on ERO1A-HIF1α-VEGFA pathway EMBO molecular medicine Medium 33751828
2017 NFIB transcriptionally activates Nfix expression in spinal cord; in the absence of Nfia or Nfib, spinal cord NFIX expression is markedly reduced, and NFIB can activate the Nfix promoter in vitro, demonstrating a hierarchical auto-regulatory transcriptional program within the NFI family during spinal cord gliogenesis. Nfia/Nfib knockout mouse spinal cord analysis, in vitro promoter reporter assay Developmental biology Medium 29106906
2017 Combined allelic loss of Nfia and Nfib in mouse cerebral cortex reveals additive/cooperative function: NFIA and NFIB are co-expressed and form heterodimers in vivo (co-immunoprecipitation). Double homozygous KO produces more severe phenotype (increased ventricular enlargement, decreased differentiated glia and neurons) than single KO. Compound Nfia/Nfib knockout mice, co-immunoprecipitation, immunofluorescence, gene expression analysis Brain and neuroscience advances Medium 32166136
2020 NFIB facilitates replication licensing by associating physically with the pre-replication complex (pre-RC) in mammalian cells; NFIB increases chromatin accessibility at replication origins, binds to and opens nucleosomes (single-molecule magnetic tweezers), and promotes nucleosome eviction (TEM); NFIB deficiency alters chromosome contacts/compartments in G1 and S phase and impairs firing of early-replication domain origins. Co-immunoprecipitation (NFIB with pre-RC components), ChIP-seq/ATAC-seq, single-molecule magnetic tweezers (nucleosome binding/opening), transmission electron microscopy, Hi-C (chromosome contacts) Nature communications High 37604829
2023 CARM1 methylates NFIB, and methylated NFIB recruits TRIM29 as an effector molecule; CARM1 functions as a coactivator for NFIB-dependent transcription. In a mouse SCLC model, the CARM1 methylation site on NFIB and CARM1 itself are both critical for rapid SCLC onset; CARM1 and methylated NFIB maintain similar open chromatin states in tumors. Biochemical substrate identification, co-IP (NFIB-CARM1, NFIB-TRIM29), mouse SCLC model with methylation-site mutant NFIB, ATAC-seq Nature communications High 36690626
2022 NFIB regulates hepatic CYP2D6 expression: NFIB inhibits CYP2D6 gene expression in Huh7 cells and 3D liver spheroids; carriers of NFIB rs28379954 T>C polymorphism have reduced NFIB expression and elevated risperidone hydroxylation rates (equivalent to CYP2D6 ultrarapid metabolizers), demonstrating NFIB as a transcriptional regulator of CYP2D6 in vivo. 3D liver spheroid and Huh7 cell overexpression/inhibition, in vivo pharmacokinetic analysis in 604 patients genotyped for NFIB and CYP2D6 Clinical pharmacology and therapeutics High 35253216
2021 NFIB directly binds the NDUFA4L2 promoter region and promotes its transcription; NFIB-upregulated NDUFA4L2 inhibits sorafenib-induced reactive oxygen species accumulation, conferring sorafenib resistance in hepatocellular carcinoma cells. ChIP (NFIB binding to NDUFA4L2 promoter), NFIB knockdown in HCC cells, ROS measurement, drug sensitivity assays Cancer science Medium 36369883
2024 NFIB directly binds promoters of CDH1 (E-cadherin) and VIM (vimentin) to regulate EMT-related transcription independently of canonical EMT transcription factors; NFIB protein stability in AR-negative CRPC is regulated by m6A: YTHDF2 recognizes m6A-methylated NFIB mRNA to increase its stability, while downregulation of TRIM8 (its E3 ubiquitin ligase, itself translationally reduced by m6A modification via ALKBH5 reduction) increases NFIB protein stability. ChIP (NFIB at CDH1 and VIM promoters), NFIB loss-of-function, m6A-RIP/MeRIP, YTHDF2 and TRIM8 functional studies, in vivo metastasis Cancer research High 38536119
2021 NFIB directly binds the PINK1 promoter and transcriptionally regulates PINK1 expression in kidney renal clear cell carcinoma, promoting tumor progression and metastasis. ChIP (NFIB at PINK1 promoter), NFIB knockdown, in vitro migration/invasion assays PeerJ Medium 33981484
2019 NFIB binds the ITGA6 promoter (chromatin immunoprecipitation) in colorectal cancer cells and activates ITGA6 transcription to promote cell metastasis; miR-302a directly targets the NFIB 3'-UTR (luciferase reporter assay) to suppress this pro-metastatic NFIB→ITGA6 axis. ChIP (NFIB at ITGA6 promoter), luciferase 3'-UTR reporter assay, functional migration/invasion assays Theranostics Medium 31754405
2025 NFIB promotes NFIB-ITGA6-driven metastasis as a direct transcriptional activator of ITGA6; separately, circHIF1A modulates NFIB expression and nuclear translocation through posttranscriptional and posttranslational mechanisms, leading to AKT/STAT3 pathway activation and p21 inhibition in TNBC; NFIB in turn transcriptionally regulates FUS, forming a circHIF1A/NFIB/FUS positive feedback loop. Gain/loss-of-function in TNBC cells and xenografts, posttranslational modification analysis, RNA-protein interaction studies Oncogene Medium 33714984
2017 NFIB interacts physically with the estrogen receptor ESR1-FOXA1 complex (co-immunoprecipitation) and inhibits ESR1 transactivational potential; FGFR2 signaling augments these interactions to further repress ESR1 target gene expression. Co-immunoprecipitation, gene expression reporter assays, FGFR2 signaling inhibition Cancer research Medium 29180470
2020 KDM4D histone demethylase physically interacts with NFIB and MLL1 complex; KDM4D-mediated demethylation of H3K9me3 is required for NFIB and MLL1 complex to deposit H3K4me3 and activate PPARγ and C/EBPα expression during adipogenesis, placing NFIB in a defined chromatin-remodeling hierarchy for adipogenic differentiation. Co-IP (KDM4D-NFIB-MLL1), ChIP (NFIB and MLL1 at target promoters), KDM4D KD/rescue in C3H10T1/2 cells Scientific reports Medium 32080306
2015 HIV-1 infection induces NF-IB (NFIB) expression, and NFIB associates with the HIV-1 long terminal repeat (LTR) region (−386 to −453 nt) as shown by ChIP assay; this association negatively correlates with HIV-1 transcription. NFIB knockdown increases HIV-1 replication in latently infected cells, indicating a repressive role of NFIB at the LTR. ChIP assay (NFIB at HIV-1 LTR), siRNA knockdown of NFIB in J1.1 and J-Lat cells, viral replication measurement Viruses Medium 25664610
2021 NFIB overexpression in hPSC-derived neural precursor cells induces differentiation into functional astrocytes within 2 weeks, recapitulating in vivo astrogliogenesis transcriptomically and physiologically; the MAPK pathway is necessary for NFIB-driven astrocyte differentiation. NFIB overexpression in hPSC-derived NPCs, RNA-seq, functional astrocyte assays, MAPK pathway inhibition Journal of cellular physiology Medium 33949692
2024 Using conditional gene knockout in SCLC GEMMs, NFIB upregulation contributes to tumor progression but is not strictly required for metastasis; FOXA1/2 pioneer transcription factors were identified as candidate drivers of metastasis in NFIB-knockout SCLC tumors, revealing SCLC plasticity and NFIB-independent metastatic mechanisms. Conditional Nfib knockout in SCLC GEMMs, molecular profiling of NFIB WT vs. KO tumors, identification of FOXA1/2 as compensatory factors Cancer research High 37963187
2014 NFIB ChIP-seq in mouse lung at E16.5 shows NFIB binds the NFI consensus motif in vivo; this motif is over-represented in promoters of genes under-expressed in Nfib-KO lung at E18.5, indicating NFIB acts as a transcriptional activator of lung maturation genes; 52 genes are co-regulated by NFIB and the glucocorticoid receptor (Nr3c1), overlapping 13.1-fold above chance. ChIP-seq (NFIB in lung E16.5), microarray (Nfib-KO and Nr3c1-KO), motif analysis BMC genomics Medium 24661679
1998 NFIB is identified as a recurrent translocation partner gene of HMGIC (HMGA2) in pleomorphic adenomas of the salivary glands; 3'-RACE and RT-PCR analyses reveal chimeric transcripts where the last five amino acids of NFIB replace the carboxy-terminal segment of HMGIC, established in two independent adenoma cases. 3'-RACE analysis, RT-PCR, nucleotide sequencing of fusion transcripts Oncogene High 9484777
2009 The t(6;9)(q22-23;p23-24) translocation in adenoid cystic carcinoma creates MYB-NFIB fusion transcripts predominantly consisting of MYB exon 14 linked to the last coding exon(s) of NFIB; the minimal deleted region includes MYB exon 15/3'-UTR containing conserved miR-15a/16 and miR-150 target sites, suggesting loss of miRNA-mediated repression of MYB leads to MYB-NFIB overexpression and activation of MYB target genes. RT-PCR, nucleotide sequencing, forced miRNA overexpression in primary ACC cells, molecular characterization of translocation breakpoints Proceedings of the National Academy of Sciences High 19841262
2020 In pleomorphic adenomas, NFIB fusions with PLAG1 (NFIB-PLAG1) and HMGA2 result in activation of PLAG1 and HMGA2 through promoter swapping; analysis of the NFIB chromatin landscape reveals super-enhancers in the 5'- and 3'-parts of the NFIB locus, suggesting PLAG1 and HMGA2 are activated by enhancer-hijacking events in which NFIB super-enhancers are translocated upstream of these oncogenes. RNA-seq, RT-PCR (fusion transcript identification), chromatin landscape analysis (super-enhancer identification) Genes, chromosomes & cancer Medium 32654217
2023 NFIB downregulates miR-182-5p, which directly targets NAMPT (the rate-limiting enzyme of NAD+ salvage synthesis); this NFIB→miR-182-5p→NAMPT axis promotes NAD+ production and colorectal cancer cell proliferation; NAD+ precursor NMN supplementation rescues proliferation in NFIB-knockdown cells. NFIB KD/OE in CRC cells, miRNA profiling, luciferase 3'-UTR reporter (miR-182-5p→NAMPT), NAD+ measurement, NMN rescue Communications biology Medium 37491379

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 624 19841262
2016 Nfib Promotes Metastasis through a Widespread Increase in Chromatin Accessibility. Cell 297 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 275 21572406
2005 The transcription factor gene Nfib is essential for both lung maturation and brain development. Molecular and cellular biology 251 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 237 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 168 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 124 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 124 21976542
2016 Transcription Factor NFIB Is a Driver of Small Cell Lung Cancer Progression in Mice and Marks Metastatic Disease in Patients. Cell reports 122 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 86 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
2016 Multipotency of Adult Hippocampal NSCs In Vivo Is Restricted by Drosha/NFIB. Cell stem cell 79 27545503
2017 MYBL1 rearrangements and MYB amplification in breast adenoid cystic carcinomas lacking the MYB-NFIB fusion gene. The Journal of pathology 78 29149504
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 69 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 65 28594149
2017 ERα Binding by Transcription Factors NFIB and YBX1 Enables FGFR2 Signaling to Modulate Estrogen Responsiveness in Breast Cancer. Cancer research 64 29180470
2016 NFIB overexpression cooperates with Rb/p53 deletion to promote small cell lung cancer. Oncotarget 61 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 50 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 45 30388402
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
2018 NFIB promotes cell survival by directly suppressing p21 transcription in TP53-mutated triple-negative breast cancer. The Journal of pathology 41 30350349
2021 YAP regulates alveolar epithelial cell differentiation and AGER via NFIB/KLF5/NKX2-1. iScience 40 34466790
2024 m6A Modification Promotes EMT and Metastasis of Castration-Resistant Prostate Cancer by Upregulating NFIB. Cancer research 39 38536119
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 33 36690626
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
2020 Common Regulatory Targets of NFIA, NFIX and NFIB during Postnatal Cerebellar Development. Cerebellum (London, England) 29 31838646
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 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 Transcriptional regulation of NDUFA4L2 by NFIB induces sorafenib resistance by decreasing reactive oxygen species in hepatocellular carcinoma. Cancer science 20 36369883
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 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 20 32659236
2022 Development and Characterization of MYB-NFIB Fusion Expression in Adenoid Cystic Carcinoma. Cancers 19 35565392
2020 Activation of PLAG1 and HMGA2 by gene fusions involving the transcriptional regulator gene NFIB. Genes, chromosomes & cancer 19 32654217
2020 MicroRNA-138-5p targets the NFIB-Snail1 axis to inhibit colorectal cancer cell migration and chemoresistance. Cancer cell international 19 33013202
2019 Transcription factors NFIA and NFIB induce cellular differentiation in high-grade astrocytoma. Journal of neuro-oncology 19 31760595
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
2021 NFIB induces functional astrocytes from human pluripotent stem cell-derived neural precursor cells mimicking in vivo astrogliogenesis. Journal of cellular physiology 18 33949692
2021 CircATL2 enhances paclitaxel resistance of ovarian cancer via impacting miR-506-3p/NFIB axis. Drug development research 18 34541682
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
2022 Transcriptional Regulation of RIP2 Gene by NFIB Is Associated with Cellular Immune and Inflammatory Response to APEC Infection. International journal of molecular sciences 16 35409172
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.] 14 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
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
2021 NFIA and NFIB function as tumour suppressors in high-grade glioma in mice. Carcinogenesis 12 33346791
2024 Small Cell Lung Cancer Plasticity Enables NFIB-Independent Metastasis. Cancer research 11 37963187
2023 NFIB facilitates replication licensing by acting as a genome organizer. Nature communications 11 37604829
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
2023 Downregulation of miR-182-5p by NFIB promotes NAD+ salvage synthesis in colorectal cancer by targeting NAMPT. Communications biology 10 37491379
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