Affinage

Showing NFIL3 — E4BP4 is a alias.

NFIL3

Nuclear factor interleukin-3-regulated protein · UniProt Q16649

Length
462 aa
Mass
51.5 kDa
Annotated
2026-06-10
100 papers in source corpus 65 papers cited in narrative 64 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NFIL3 (E4BP4) is a basic leucine-zipper transcription factor that integrates cytokine and metabolic signals to control immune cell development, circadian gene expression, and hepatic lipid and glucose metabolism, acting predominantly as a repressor but also as a context-dependent activator (PMID:11316793, PMID:19749763, PMID:19995955, PMID:24663216). Its repressor function is conferred by a discrete C-terminal 65-amino-acid domain that recruits the TBP-binding co-repressor Dr1, and is amplified by epigenetic co-repressors including the histone methyltransferase G9a and the HDAC1/EZH2 machinery (PMID:8127655, PMID:8836190, PMID:23283977, PMID:32191636). In the circadian clock NFIL3 oscillates in antiphase to the PAR factors (DBP/HLF/TEF), competing for shared D-box sites to repress targets such as Per2, Fgf21, Nampt, and Bmp4, thereby setting period and amplitude (PMID:11316793, PMID:17182630, PMID:20851878, PMID:35036997, PMID:24794868). In immunity NFIL3 is an essential cell-intrinsic factor acting downstream of IL-15 via a PDK1–mTORC1 axis to drive NK cell and innate lymphoid cell commitment through direct transactivation of Id2, Eomes, TOX, and Notch1, and it independently directs CD8α+/cDC1 dendritic cell development through Batf3 and a Zeb2–Id2 circuit (PMID:19749763, PMID:19995955, PMID:24663216, PMID:25310240, PMID:25801035, PMID:25624444, PMID:31406377, PMID:29311361). Beyond lineage specification NFIL3 tunes effector function by repressing Il12b in myeloid cells, repressing Bcl6 to limit Tfh differentiation, repressing Foxp3 in Tregs, and driving Tim-3/IL-10 co-expression downstream of IL-27 (PMID:21383239, PMID:21566115, PMID:25614966, PMID:32191636, PMID:31311918). In the liver NFIL3 suppresses gluconeogenesis by competing with CREB at CRE sites, while promoting de novo lipogenesis by stabilizing nuclear SREBP-1c and, after HFD-induced deSUMOylation, transactivating the lipid-droplet gene Fsp27 via CREBH (PMID:27252523, PMID:29132537, PMID:36508222). NFIL3 protein abundance and activity are set post-translationally by CK1ε-mediated Ser182 phosphorylation that triggers proteasomal degradation, by SUMOylation, by sulfhydrylation, and translationally by hnRNP A1-dependent IRES activity (PMID:15182670, PMID:36508222, PMID:28220845, PMID:38049061).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1994 High

    Established that NFIL3 acts as a transcriptional repressor through a defined, transferable domain rather than as a generic DNA binder, localizing its repressive function molecularly.

    Evidence deletion mapping, GAL4 fusion reporters, and charge-mutagenesis of a 65-aa C-terminal domain

    PMID:8127655

    Open questions at the time
    • The general transcription machinery contact was inferred, not identified
    • Did not establish the in vivo target genes repressed via this domain
  2. 1995 High

    Showed NFIL3 can also act as a sequence-specific activator, demonstrating its dual transcriptional capacity depends on promoter context.

    Evidence DNase I footprinting, EMSA, and cotransfection reporter assays on the IL-3 promoter

    PMID:7565758

    Open questions at the time
    • Mechanism switching between activation and repression unresolved
    • No co-factor identified for activation
  3. 1996 Medium

    Identified the co-repressor Dr1 as the molecular mediator of NFIL3 repression, connecting the repression domain to the basal transcription machinery.

    Evidence in vitro protein binding with repression-defective mutant correlation

    PMID:8836190

    Open questions at the time
    • Single in vitro binding method without reciprocal validation
    • Not shown on an endogenous target gene
  4. 1997 High

    Placed NFIL3 downstream of cytokine survival signaling, showing it transduces IL-3 anti-apoptotic signals in lymphoid progenitors.

    Evidence Northern blot, cytokine-withdrawal survival assay, and cDNA overexpression in pro-B cells

    PMID:9122243

    Open questions at the time
    • Pro-survival target genes not defined
    • Relationship between repressor activity and survival function unclear
  5. 2001 High

    Embedded NFIL3 in the core circadian oscillator as the negative D-box regulator opposing PAR activators through DNA-site competition.

    Evidence in situ hybridization, luciferase reporters, EMSA, and Cry-knockout mouse analysis in SCN and liver

    PMID:11316793

    Open questions at the time
    • Direct clock target genes not yet enumerated
    • Mechanism placing E4bp4 downstream of CRY not fully resolved
  6. 2004 High

    Defined the principal post-translational control of NFIL3 stability, showing CK1ε phosphorylation at Ser182 drives proteasomal degradation and limits repression.

    Evidence co-IP, in vitro kinase assay, proteasome inhibition, site-directed mutagenesis, and reporter assays

    PMID:15182670

    Open questions at the time
    • Phosphatase counteracting CK1ε not identified
    • Whether degradation is gated by circadian or signaling inputs unresolved
  7. 2006 High

    Provided direct in vivo evidence that NFIL3 represses a clock gene by binding the Per2 promoter B-site, mechanizing its circadian role.

    Evidence siRNA knockdown, reporter mutagenesis, and ChIP correlating peak binding with trough Per2 mRNA

    PMID:17182630

    Open questions at the time
    • Co-repressors recruited at the Per2 B-site not identified at this stage
  8. 2009 High

    Identified NFIL3 as a non-redundant, cell-intrinsic master regulator of NK cell development acting downstream of IL-15 and upstream of Id2.

    Evidence two independent Nfil3-/- mouse lines, bone marrow chimeras, and progenitor overexpression

    PMID:19749763 PMID:19995955

    Open questions at the time
    • Direct vs indirect regulation of Id2 not yet shown by ChIP
    • Developmental stage of NFIL3 requirement undefined
  9. 2011 High

    Broadened NFIL3's immune role beyond NK cells to dendritic cell development and cytokine programming, including IL-12p40 repression and IL-10/IL-13 control.

    Evidence Nfil3-/- mice, ChIP on Il12b/Il13 loci, enhancer mutagenesis, and gain/loss-of-function across DC and T cell subsets

    PMID:21383239 PMID:21460847 PMID:21474667 PMID:21499227 PMID:21566115

    Open questions at the time
    • Whether the same repression machinery operates across all loci unclear
    • Direct vs Batf3-mediated DC effects not fully separated
  10. 2013 High

    Mechanized NFIL3 repression epigenetically by showing direct recruitment of G9a to deposit H3K9me2 at the Fgf21 promoter.

    Evidence co-IP, G9a catalytic-mutant and inhibitor, H3K9me2 ChIP, and in vivo G9a depletion

    PMID:23283977

    Open questions at the time
    • Generality of G9a recruitment to other NFIL3 targets not established here
  11. 2014 High

    Resolved the transcriptional circuitry of NFIL3-driven lymphopoiesis, showing direct activation of Eomes, Id2, and TOX at the common lymphoid/ILC precursor stage.

    Evidence ChIP, retroviral Eomes/Id2 rescue of Nfil3-/- progenitors, and stage-specific conditional analysis

    PMID:24277151 PMID:24532575 PMID:24663216 PMID:25310240

    Open questions at the time
    • Why NFIL3 is required only early/transiently in NK lineage not fully explained
    • Eomes-independent TRAIL+ NK pathway mechanism unclear
  12. 2015 High

    Connected upstream signaling to NFIL3 induction, defining a PDK1–mTOR–E4BP4–CD122 feedback loop downstream of IL-15 and an IL-27–NFIL3–Tim-3/IL-10 dysfunction axis.

    Evidence conditional PDK1 KO with mTOR/E4BP4 rescue, and IL-27R-/- mice with chromatin accessibility assays

    PMID:25614966 PMID:25624444

    Open questions at the time
    • Direct mTORC1 target driving E4bp4 transcription not identified
    • How IL-27 vs IL-15 inputs are integrated at the Nfil3 locus unclear
  13. 2016 High

    Established NFIL3 as a hepatic metabolic regulator that stabilizes nuclear SREBP-1c to promote de novo lipogenesis.

    Evidence co-IP, ubiquitination/acetylation assays, adenoviral liver depletion, and E4bp4-/- hepatocytes

    PMID:27252523

    Open questions at the time
    • How NFIL3 preserves SREBP-1c acetylation mechanistically not resolved
  14. 2017 High

    Linked NFIL3 to systemic and intestinal metabolic control, integrating microbiota, ILC3, and circadian inputs to regulate epithelial lipid handling.

    Evidence germ-free, ILC3-depleted, and Nfil3-/- mice with STAT3 pathway analysis and lipid absorption assays; plus IRES translational regulation

    PMID:28220845 PMID:28860383

    Open questions at the time
    • Direct epithelial lipid-gene targets of NFIL3 incompletely mapped
    • How circadian and microbial signals are integrated at the locus unresolved
  15. 2017 High

    Showed NFIL3 represses gluconeogenesis and is itself a Smad3 target, expanding its metabolic and developmental regulatory network.

    Evidence ChIP, reporter competition with CREB, in vivo hepatic rescue of hyperglycemia, and Smad3-/- NK differentiation

    PMID:28262747 PMID:29132537

    Open questions at the time
    • Whether CREB competition uses the same DNA element in all gluconeogenic promoters unclear
  16. 2018 High

    Mechanized NFIL3 repression in adaptive immunity through HDAC1/EZH2 recruitment at Bcl6, and tied its activity to phosphorylation status relevant to autoimmunity.

    Evidence conditional KO/KI T cells, ChIP for HDAC1/EZH2 recruitment, phospho-mutants, and SLE patient samples

    PMID:29311361 PMID:32191636

    Open questions at the time
    • Kinase/phosphatase controlling the relevant phosphosite in T cells not pinpointed
    • Notch1 as direct target needs further validation beyond rescue
  17. 2019 High

    Defined the upstream and downstream architecture of NFIL3-dependent cDC1 development and added drug-metabolism and Treg targets to its repertoire.

    Evidence scRNA-seq and genetic epistasis (Nfil3/Zeb2/Id2), PBX1 ChIP and promoter binding-site CRISPR KO, and Cyp3a11/Foxp3 ChIP with KO pharmacokinetics

    PMID:30796914 PMID:31311918 PMID:31406377 PMID:32190943

    Open questions at the time
    • Integration of PBX1 and cytokine inputs at the Nfil3 promoter unresolved
    • Direct vs methylation-mediated Foxp3 repression mechanism incompletely separated
  18. 2021 High

    Embedded NFIL3 in a REV-ERB→E4BP4→NAMPT→NAD+ circadian metabolic pathway controlling cardiac homeostasis.

    Evidence cardiomyocyte-specific Rev-erb double KO, ChIP at Nampt enhancers, and NAD+ metabolite measurement

    PMID:35036997

    Open questions at the time
    • Tissue specificity of the NAMPT regulation not generalized
  19. 2023 High

    Revealed SUMOylation as a metabolic switch and a CREBH partnership controlling lipid-droplet gene Fsp27, refining NFIL3's pro-steatotic role.

    Evidence SUMOylation-site mutants, co-IP for CREBH, HFD liver-specific KO, and Fsp27 rescue

    PMID:36508222 PMID:39473081

    Open questions at the time
    • The deSUMOylating enzyme acting on E4BP4 after HFD not identified
    • How SUMOylation status reprograms target selection mechanistically unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single bZIP factor selects between repression (Dr1/G9a/HDAC1/EZH2) and activation, and how its many post-translational modifications (phosphorylation, SUMOylation, sulfhydrylation) and translational IRES control are coordinately decoded to specify distinct immune, circadian, and metabolic outputs, remains unresolved.
  • No unified model linking PTM state to target-gene choice
  • No structural basis for activator vs repressor mode
  • Cross-talk between circadian, immune, and metabolic programs in vivo not integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-168256 Immune System 6 R-HSA-1430728 Metabolism 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-9909396 Circadian clock 5 R-HSA-1266738 Developmental Biology 4
Partners
CK1ΕCREBHDR1EZH2G9AHDAC1PER2SREBP-1C

Evidence

Reading pass · 64 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 E4BP4 transcriptional repression was mapped to a minimal 65-amino-acid domain near the C-terminus; a charge-configuration mutation in this domain abolished repressor activity. The mechanism involves interaction with components of the general transcription machinery rather than resembling known Krüppel/Engrailed repression domains. Deletion mapping, GAL4 fusion reporter assays, mutagenesis Nucleic Acids Research High 8127655
1995 NF-IL3A (NFIL3) binds the IL-3 promoter footprint A region (TAATTACGTCTG; minimal site ATTACG) and acts as a transcriptional activator of the IL-3 promoter in resting T cells; the binding site is required for transactivation. DNase I footprinting, gel shift assay, cotransfection reporter assay Molecular and Cellular Biology High 7565758
1995 E4BP4 protein produced in Sf9 insect cells is phosphorylated, and this phosphorylation enhances its DNA-binding activity compared with bacterially produced (unphosphorylated) protein. Baculovirus expression, gel shift assay, post-translational modification analysis Biochimica et Biophysica Acta Medium 8547328
1996 The E4BP4 repression domain interacts specifically with the TBP-binding repressor protein Dr1; E4BP4 mutants defective in repression are also deficient in Dr1 binding, indicating that Dr1 recruitment mediates E4BP4 transcriptional repression. Protein–protein interaction assay (in vitro binding), repression-domain mutant analysis Nucleic Acids Research Medium 8836190
1997 NFIL3/E4BP4 expression is regulated by IL-3 in murine pro-B cells as a delayed-early gene requiring de novo protein synthesis; enforced NFIL3 expression promotes survival (but not growth) of IL-3-deprived pro-B cells, positioning NFIL3 downstream of IL-3 in an anti-apoptotic signaling pathway. Northern blot, cytokine withdrawal survival assay, cDNA overexpression Proceedings of the National Academy of Sciences High 9122243
1997 E4BP4 mRNA is induced by the synthetic glucocorticoid dexamethasone in mouse fibroblasts, and E4BP4-binding elements are present in the promoters of glucocorticoid-repressed genes COX-2, iNOS, and cPLA2, suggesting E4BP4 mediates glucocorticoid gene repression. cDNA subtraction screening, Northern blot, promoter sequence analysis Biochemical and Biophysical Research Communications Low 9125190
1999 NFIL3 expression is regulated by oncogenic Ras through both the Raf-MAPK and PI3K pathways in IL-3-dependent pro-B cells; NFIL3-mediated survival is independent of Bcl-xL, defining two parallel IL-3 survival pathways. Oncogenic Ras mutants, kinase pathway inhibitors, survival assays Molecular and Cellular Biology Medium 10082541
1999 E4BP4 represses HBV core promoter and enhancer II transcription; its repressive mechanism requires DNA binding (binding site occlusion) and does not strictly require a separate repression domain beyond the DNA-binding domain. Transient transfection reporter assay, E4BP4 overexpression, antisense experiments Journal of Virology Medium 10074173
2000 E4BP4 binds to HBV enhancer II (nucleotides 1640–1663) and suppresses its transcriptional activity, in contrast to HLF and FTF which activate the same element. Yeast one-hybrid screening, transcriptional activity assays Journal of Virology Medium 10627534
2001 E4BP4 oscillates in antiphase to the PAR transcription factors (DBP, HLF, TEF) in the SCN and liver; E4BP4 suppresses while PAR proteins activate transcription from the shared PAR/E4BP4 binding site; E4BP4 cannot dimerize with PAR proteins but competes for the same DNA sites. In Cry-deficient mice, E4bp4 levels are sustained low while dbp is high, placing E4BP4 within the core circadian oscillatory mechanism. In situ hybridization, luciferase reporter assay, EMSA, Cry-knockout mouse analysis Genes & Development High 11316793
2002 IL-3-dependent transcription of E4bp4 requires a GATA motif downstream of the major transcription start site; both GATA-1 and GATA-2 bind this site in vitro and in vivo, with GATA-1 binding confirmed by ChIP; GATA-1 overexpression transactivates the E4bp4 reporter and modulates apoptosis on IL-3 withdrawal. Promoter deletion analysis, EMSA, chromatin immunoprecipitation, overexpression/apoptosis assay Journal of Biological Chemistry High 12023274
2003 PTH rapidly and transiently induces E4BP4 as a primary response gene in osteoblasts (no protein synthesis required); E4BP4 overexpression inhibits EBPRE-containing promoters and attenuates PTH-induced COX-2 promoter activity in osteoblasts. Northern blot, cycloheximide experiments, reporter assay, E4BP4 overexpression Journal of Biological Chemistry Medium 12743120
2004 Casein kinase 1ε (CK1ε) physically associates with E4BP4 and phosphorylates it at Ser182; CK1ε-catalyzed phosphorylation leads to proteasomal degradation of E4BP4 and attenuates E4BP4 nuclear accumulation and transcriptional repression of cPer2. Co-immunoprecipitation, in vitro kinase assay, proteasome inhibitor experiments, site-directed mutagenesis, luciferase reporter assay Current Biology High 15182670
2004 E4BP4 overexpression protects embryonic motoneurons from apoptosis induced by neurotrophic factor withdrawal or death receptor activation, and promotes neuronal cell size and axonal growth (3.5-fold longer axons) in a PI3K-dependent manner; in vivo overexpression in chick embryos reduced dying motoneurons by 45%. Motoneuron electroporation, survival and axon growth assays, PI3K inhibition, in ovo overexpression Development Medium 15306565
2004 E4BP4 represses VWF promoter activity by binding a negative response element at nucleotides +96/+105 of the VWF promoter in vivo, as demonstrated by ChIP; the repressive mechanism is cell-type specific (larger E4BP4 forms bind DNA in HepG2 cells; smaller forms in endothelial cells do not bind directly but may sequester co-repressors). Chromatin immunoprecipitation, promoter reporter assays, site mutagenesis Blood Medium 15498853
2006 E4BP4 negatively regulates Per2 mRNA oscillation by binding a specific B-site in the mPer2 promoter; ChIP shows peak E4BP4 binding corresponds to trough Per2 mRNA; both the B-site and the E2 enhancer are required for robust circadian Per2 oscillation in the cell-autonomous clock. siRNA knockdown, luciferase reporter assay with promoter mutants, chromatin immunoprecipitation Nucleic Acids Research High 17182630
2007 E4BP4 physically interacts with PER2 (requiring the C-terminal repression domain) and with CRY2; these interactions place E4BP4 in a negative regulator complex of the mammalian circadian clock. Co-immunoprecipitation, deletion mutant analysis Biochemical and Biophysical Research Communications Medium 17274955
2009 E4BP4/NFIL3 is essential for NK cell development in a cell-intrinsic manner, acting downstream of the IL-15 receptor and upstream of (and through) the transcription factor Id2; E4BP4-deficient mice specifically lack NK cells while retaining B, T, and NKT cells. Nfil3-/- mouse generation, bone marrow reconstitution, cytotoxicity assays, hematopoietic progenitor overexpression Nature Immunology High 19749763 19995955
2009 NFIL3 is required for IgE class switching in a B-cell-intrinsic manner; NFIL3 binds the Iε promoter in vivo (ChIP) and is required for IL-4/LPS-induced germline epsilon (GLε) transcript production; NFIL3 expression in NFIL3-deficient B cells restores GLε transcription. Nfil3-/- mice, B-cell chimeras, chromatin immunoprecipitation, rescue experiments, cycloheximide GLε induction Proceedings of the National Academy of Sciences High 20080759
2010 E4BP4 represses FGF21 transcription by binding a D-box element in the distal Fgf21 promoter; this repression is insulin-responsive via AKT-mediated induction of E4BP4. E4BP4 knockdown augments Fgf21 oscillation amplitude and overexpression represses FGF21 secretion from primary hepatocytes. ChIP, luciferase reporter assay, siRNA knockdown, overexpression in hepatocytes, D-box mutagenesis Journal of Biological Chemistry High 20851878
2011 NFIL3/E4BP4 is essential for CD8α+ conventional dendritic cell development; Nfil3-/- mice specifically lack CD8α+ cDCs but retain CD8α- cDCs and pDCs. NFIL3 regulates CD8α+ cDC development partly through Batf3 expression; loss of NFIL3 impairs cross-priming of CD8+ T cells and IL-12 production after TLR3 stimulation. Nfil3-/- mice, bone marrow reconstitution, Flt3L cultures, T cell cross-priming assay, cytokine production assay Blood High 21474667
2011 NFIL3 is a negative regulator of IL-12 p40 (Il12b) transcription in macrophages; NFIL3 binds the Il12b promoter (confirmed by ChIP); NFIL3 is induced by IL-10/STAT3 signaling and its repression of Il12b does not require IL-10 but requires a C-terminal minimal repression domain. ChIP, luciferase reporter with BAC-GFP reporter line, shRNA knockdown, Nfil3-/- mice Journal of Immunology High 21383239
2011 A single NFIL3-binding site 10 kb upstream of Il12b is required for IL-10/STAT3-mediated repression of IL-12p40; NFIL3 binds this enhancer site and myeloid cells lacking NFIL3 overproduce IL-12p40 and IL-12p70. Enhancer deletion, ChIP, site mutagenesis, Nfil3-/- myeloid cells Journal of Biological Chemistry High 21566115
2011 E4BP4 regulates IL-10 and IL-13 production in CD4+ T cells: enforced E4BP4 expression drives IL-10 and IL-13 production in Th1 cells; E4bp4-/- Th1 cells, Treg cells, and NKT cells show attenuated IL-10 and IL-13; E4bp4-/- Th2 cells show impaired IL-10 (but not IL-13) production. Nfil3-/- mice, retroviral overexpression, cytokine ELISA and intracellular staining Nature Immunology High 21460847
2011 NFIL3 directly binds and negatively regulates the Il13 gene in Th2 cells; NFIL3 deficiency increases IL-13 and IL-5 but decreases IL-4 production in a T-cell-intrinsic manner. ChIP, retroviral NFIL3 expression, Nfil3-/- Th2 cell cytokine analysis EMBO Journal High 21499227
2011 DBP (positive D-box regulator) knockdown shortens the circadian period of Per1/Per2 reporters in fibroblasts, while E4BP4 (negative D-box regulator) knockdown has the opposite effect; overexpression produces reciprocal phenotypes, demonstrating that D-box regulators including E4BP4 determine circadian period length. siRNA knockdown, cDNA overexpression, bioluminescent reporter assay in Rat-1 fibroblasts FEBS Letters Medium 21635892
2013 E4BP4 represses Fgf21 via recruitment of histone methyltransferase G9a, which catalyzes H3K9me2 at the Fgf21 promoter; E4BP4 physically interacts with G9a; G9a SET-domain deletion abolishes repression; acute hepatic G9a knockdown de-represses Fgf21 during refeeding. Co-immunoprecipitation, G9a inhibitor (BIX01294), H3K9me2 ChIP, overexpression, shRNA knockdown, adenoviral G9a depletion in vivo Journal of Biological Chemistry High 23283977
2013 Nfil3 is required only early during NK cell development (at or before the NK progenitor stage); specific deletion in mature peripheral NK cells or immature BM NK cells has no effect on lineage maintenance; viral signals (Ly49H engagement, proinflammatory cytokines) can bypass Nfil3 to generate Ly49H+ NK cells in Nfil3-/- mice infected with MCMV. Conditional Nfil3 deletion (immature/mature NK stages), MCMV infection model, memory NK cell persistence assay Journal of Experimental Medicine High 24277151
2013 Nfil3 is required for glucocorticoid-induced apoptosis (GICD) in T cells; a glucocorticoid response element 5 kb upstream of the Nfil3 promoter is bound by GR (confirmed by ChIP); Nfil3 siRNA knockdown to 20% of normal abrogates GICD in CTLL-2 T cells. Microarray, ChIP, siRNA knockdown, apoptosis assay Endocrinology Medium 23425966
2014 E4BP4 binds directly to the regulatory regions of both Eomes and Id2 genes and promotes their transcription; E4BP4 is required at the CLP stage for NK lineage commitment; forced Eomes and Id2 expression can rescue NK production from E4bp4-/- progenitors. ChIP, progenitor rescue experiments with retroviral Eomes/Id2, CLP-stage conditional analysis Journal of Experimental Medicine High 24663216
2014 NFIL3 directs differentiation of a committed ILC precursor (αLP/CXCR6+ cells) that gives rise to all ILC lineages; NFIL3 was required in the CLP and directly regulates TOX expression to govern ILC development. Nfil3-/- mice, clonal differentiation assays, conditional knockouts, ChIP for TOX regulation eLife High 25310240
2014 Nfil3 is required for formation of Eomes-expressing NK cells (conventional medullary and thymic NK), but TRAIL+ Eomes- NK cells develop independently of Nfil3; restoration of Eomes in Nfil3-/- progenitors rescues conventional NK development. Nfil3-/- mice, retroviral Eomes rescue, flow cytometry phenotyping Journal of Immunology Medium 24532575
2014 NFIL3 exerts its function via direct Id2 regulation in the CHILP; ectopic Id2 expression in Nfil3-null precursors rescues ILC lineage development in vivo; IL-7 controls Nfil3 expression in lymphoid progenitors. Conditional Nfil3 ablation, Id2 rescue experiments, ChIP for Id2 regulation Cell Reports High 25801035
2014 NFIL3 is a microbiota-dependent, IL-10-independent regulator of IL-12p40 in the colon; Nfil3-/- mice develop spontaneous colitis that is abrogated by additional Il12b deletion and requires microbiota (germ-free Nfil3-/- mice are protected). Double-KO mice (Nfil3-/-/Il12b-/-), germ-free Nfil3-/- mice, CD4+ T cell adoptive transfer Journal of Immunology High 24442434
2015 IL-27 induces NFIL3 in T cells; NFIL3 promotes permissive chromatin remodeling at the Tim-3 locus and induces Tim-3 and IL-10 co-expression; IL-27/NFIL3 axis drives T cell dysfunction and reduced effector function in a NFIL3-dependent manner. IL-27R-/- mice, NFIL3 overexpression/knockdown, chromatin accessibility/histone modification assays, Tim-3 expression analysis Nature Communications High 25614966
2015 PDK1 connects IL-15 signaling to E4BP4 induction in NK cells via mTOR; PDK1-deficient NK cells show reduced mTOR activation, E4BP4 induction, and CD122 expression; ectopic E4BP4 expression or mTOR activation partially rescues NK development from PDK1-deficient progenitors, defining a PDK1-mTOR-E4BP4-CD122 positive feedback loop. Conditional PDK1 KO, retroviral E4BP4 overexpression, mTOR activation rescue, CD122 expression analysis Journal of Experimental Medicine High 25624444
2016 E4BP4 promotes survival of IL-5-stimulated eosinophils against glucocorticoid-induced apoptosis; IL-5 and dexamethasone synergistically induce NFIL3; siRNA-mediated NFIL3 inhibition or Pim-1 kinase blockade abrogates the IL-5 protective effect, identifying crosstalk between IL-5 anti-apoptotic pathways and GR transactivation via NFIL3. siRNA knockdown, Pim-1 inhibitor, apoptosis assays, proteomic analysis Apoptosis Medium 26880402
2016 E4BP4 is an insulin-induced stabilizer of nuclear SREBP-1c in hepatocytes; E4BP4 interacts with nuclear SREBP-1c to preserve its acetylation and protect it from ubiquitination-dependent degradation, thereby promoting SREBP-1c-mediated de novo lipogenesis. Co-immunoprecipitation, ubiquitination assay, acetylation assay, adenoviral shRNA liver depletion, E4bp4-/- hepatocytes Journal of Lipid Research High 27252523
2017 Smad3 directly suppresses E4BP4/NFIL3 transcription; Smad3 deletion enhances E4BP4-mediated NK cell differentiation and anti-tumor effector functions; Smad3 suppresses IFN-γ expression via E4BP4 in a T-bet-independent manner. Smad3-/- bone marrow NK differentiation, ChIP/transcription assays for E4BP4 as Smad3 target, IFN-γ assays, Smad3 inhibitor (SIS3) in vivo Nature Communications High 28262747
2017 The intestinal microbiota regulates NFIL3 transcription in intestinal epithelial cells (IECs) through group 3 ILCs, STAT3, and the epithelial circadian clock; NFIL3 controls a circadian lipid metabolic program in IECs and regulates lipid absorption and export. Nfil3-/- mice, germ-free mice, ILC3-depleted mice, STAT3 pathway analysis, lipid absorption assays, circadian gene expression Science High 28860383
2017 NFIL3 represses hepatic gluconeogenesis by competing with CREB for binding at cAMP response elements in gluconeogenic gene promoters (e.g., PEPCK, G6Pase); this requires the NFIL3 bZIP DNA-binding domain; hepatic NFIL3 is decreased in insulin-resistant mice and its ectopic expression in insulin-resistant livers ameliorates hyperglycemia. ChIP, luciferase reporter assay, adenoviral hepatic NFIL3 delivery in ob/ob and HFD mice, primary hepatocyte glucose production assays Metabolism High 29132537
2018 E4BP4 regulates carboxylesterase 2 (Ces2) enzymes by antagonizing Rev-erbα transrepression; E4BP4 directly interacts with Rev-erbα (Co-IP); Rev-erbα represses Ces2b by binding its promoter (-767 to -754 bp); E4BP4 loss down-regulates Ces2 genes and impairs CPT-11 pharmacokinetics. Co-immunoprecipitation, luciferase reporter, EMSA, E4bp4-/- mice, pharmacokinetic studies Biochemical Pharmacology High 29653076
2018 E4BP4 inhibits Tfh cell differentiation by recruiting repressive epigenetic modifiers HDAC1 and EZH2 to repress Bcl6 transcription; phosphorylation-site mutants of E4BP4 show limited capability to inhibit Tfh differentiation; E4BP4 phosphorylation is impaired in SLE patients. Conditional E4bp4 KO and knockin T cells, ChIP for HDAC1/EZH2 recruitment, phosphorylation mutant analysis, SLE patient samples Journal of Clinical Investigation High 32191636
2018 E4BP4 interacts with G9a to form a multi-molecular complex on the SOSTDC1 promoter in thyroid cancer cells, causing SOSTDC1 silencing through G9a-mediated histone methylation, which leads to deregulated hepcidin secretion and iron dysregulation promoting cancer proliferation. Co-immunoprecipitation, ChIP, siRNA knockdown, in vivo xenograft, luciferase assay Cell Death & Disease Medium 30250199
2019 NFIL3 acts as a transcriptional activator of the PRNP promoter in lung adenocarcinoma cells, driving PrPc expression; NFIL3-induced cell migration and invasion requires PrPc and proceeds through JNK signaling-dependent lamellipodium formation. Luciferase reporter assay, ChIP, PrPc knockdown, JNK inhibitor, migration/invasion assays Oncogene Medium 31477838
2019 NFIL3 directly binds and negatively regulates Foxp3 expression in Treg cells; NFIL3 overexpression in Treg cells induces methylation at Foxp3 locus CpG regulatory sites, diminishing Foxp3 and other Treg signature genes, impairing immunosuppressive activity. ChIP, bisulfite sequencing, overexpression in Treg cells, in vitro and in vivo suppression assays Experimental & Molecular Medicine Medium 31311918
2019 An Nfil3-Zeb2-Id2 genetic circuit controls cDC1 progenitor development: Nfil3 is required for transition from Zeb2hi/Id2lo CDPs to Zeb2lo/Id2hi CDPs (earliest committed cDC1 progenitors), blocking E-protein activity to exclude pDC potential. Single-cell RNA sequencing, genetic epistasis (Nfil3, Zeb2, Id2 KO combinations) Nature Immunology High 31406377
2019 E4bp4 negatively regulates Cyp3a11 expression and activity in liver, kidney, and intestine by directly binding the C-site (-1539/-1529 bp) in the Cyp3a11 promoter; E4bp4-/- mice show elevated Cyp3a11 activity and reduced systemic midazolam exposure. E4bp4-/- mice, luciferase reporter, EMSA, microsomal enzyme activity, pharmacokinetic studies Biochemical Pharmacology High 30796914
2020 PBX1 directly binds the Nfil3 promoter and upregulates NFIL3 expression to promote early NK cell development; knockout of the PBX1 binding site in the Nfil3 promoter reduces NK progenitor and NK cell numbers phenocopying Nfil3 KO; PBX1 residue N286 in the homeodomain is required for Nfil3 promoter binding. Conditional PBX1 KO, ChIP, CRISPR-mediated Nfil3 promoter binding-site KO, PBX1 homeodomain mutagenesis FASEB Journal High 32190943
2021 REV-ERBα/β repress E4BP4 transcription in cardiomyocytes; loss of Rev-erbs causes E4BP4 induction; E4BP4 directly controls circadian Nampt expression and NAD+ production via distal cis-regulatory elements; this REV-ERB→E4BP4→NAMPT→NAD+ pathway is required for cardiac metabolic homeostasis and function. Cardiomyocyte-specific Rev-erb double KO mice, ChIP for E4BP4 binding to Nampt enhancers, NAD+ metabolite measurement, dilated cardiomyopathy phenotype analysis Nature Cardiovascular Research High 35036997
2021 mTORC1 primarily promotes E4BP4 expression to regulate early NK cell differentiation (iNK stage), while both mTORC1 and mTORC2 enhance T-bet expression; mTORC2 deficiency specifically impairs CD27-CD11b- early iNK cells. CD122-Cre and Ncr1-Cre mediated conditional KO of mTOR, Raptor, Rictor; flow cytometry; E4BP4 and T-bet expression analysis Cell Death and Differentiation Medium 33462410
2021 NFIL3 promotes transcription of REDD1 by binding to its promoter; REDD1 augments neutrophil autophagy and NET formation by inhibiting mTOR; NFIL3 silencing reduces inflammatory injury in acute gouty arthritis mice by inhibiting neutrophil autophagy and NET formation via the REDD1/mTOR pathway. ChIP/luciferase for REDD1 promoter binding, NFIL3 gain/loss-of-function in neutrophils, in vivo gout model with NFIL3 silencing, autophagy and NET assays Frontiers in Medicine Medium 34660620
2022 NFIL3 directly suppresses NFKBIA transcription (confirmed by ChIP and luciferase reporter), thereby enhancing NF-κB signaling to promote TNBC cell proliferation and metastasis; NFIL3 also auto-represses its own transcription. ChIP, luciferase reporter assay, colony formation, migration, transwell assay, subcutaneous tumor model, tail-vein injection metastasis model Journal of Experimental & Clinical Cancer Research Medium 35180863
2022 E4BP4 inhibits the ERK1/2 signaling pathway in microglia by trans-repressing Mapk1/3 (genes encoding ERK1/2) via direct binding to D-box elements in their promoter regions, thereby restraining microglial activation; microglial E4bp4 deletion exacerbates delirium-associated cognitive decline. Microglial-specific E4bp4 KO, ChIP for Mapk1/3 D-box binding, scRNA-seq, ERK1/2 activation assays, cognitive behavioral tests Advanced Science Medium 35713240
2023 E4BP4 is modified by SUMOylation at five lysine residues; HFD feeding induces deSUMOylation of hepatic E4BP4; SUMOylated E4BP4 downregulates Fsp27 and lipid droplet formation, while deSUMOylated (active) E4BP4 enhances Fsp27 transactivation via CREBH interaction to promote liver steatosis. SUMOylation mutants, Co-IP for CREBH interaction, primary hepatocyte lipid assays, HFD E4bp4-LKO mice, Fsp27 overexpression rescue Diabetes High 36508222
2024 Hepatocyte E4BP4 interacts with and stabilizes YAP; E4BP4 induces OPN (osteopontin) via YAP to activate hepatic stellate cells and promote liver fibrosis; E4BP4 overexpression in hepatocytes activates HSCs in medium transfer experiments, and this is abrogated by OPN neutralization or depletion. Co-IP for E4BP4-YAP interaction, RNA-Seq, OPN antibody neutralization, shRNA Opn depletion, medium transfer HSC activation assay, hepatocyte-specific E4bp4 KO in NASH diet and CCl4 models Advanced Science High 39473081
2017 hnRNP A1 binds a specific region of the Nfil3 5'-UTR IRES and regulates cap-independent, IRES-mediated translation of Nfil3 mRNA; hnRNP A1 knockdown abolishes Nfil3 protein oscillation without affecting mRNA oscillation, revealing a post-transcriptional layer of circadian Nfil3 regulation. IRES reporter assay, RNA pulldown, hnRNP A1 knockdown, circadian protein/mRNA tracking Scientific Reports Medium 28220845
2018 E4BP4 SUMOylation and phosphorylation modulate its function and NK cell development; a novel E4bp4 target gene is Notch1; abrogation of Notch signaling impedes NK cell production; complete absence of NK development from E4bp4-/- progenitors is fully rescued by short exposure to Notch peptide ligands. Post-translational modification mutants, Notch ChIP/reporter identification, Notch ligand rescue of NK progenitors, NK cell development assays Journal of Immunology Medium 29311361
2020 E4BP4 promotes hepatic lipid accumulation by suppressing AMPK activity through promotion of AMPKβ1 ubiquitination and degradation; hepatic E4bp4 induction by ER stress (tunicamycin, HFLMCD diet) is partially dependent on CHOP and requires an E-box in the E4bp4 promoter. E4bp4 liver-specific KO mice, AMPKβ1 ubiquitination assay, primary hepatocyte lipid assays, AMPKβ1 depletion rescue, promoter E-box mutation analysis FASEB Journal Medium 32780887
2014 E4BP4 directly represses SOSTDC1 expression in breast cancer cells; E4BP4 binding regions in the SOSTDC1 promoter were identified by deletion analysis; E4BP4 knockdown combined with demethylation treatment up-regulates SOSTDC1 and inhibits cell proliferation. Promoter deletion/reporter assay, E4BP4 knockdown, 5'-Aza-dC treatment, cell proliferation assay Cellular Oncology Low 25338303
2004 PTH induces E4bp4 mRNA expression in osteoblasts primarily through cAMP-PKA signaling; PKA inhibitor H89 blocks PTH- and forskolin-induced E4bp4; PTH(3-34) (lacking cAMP activation) does not induce E4bp4; this pathway is confirmed in vivo. Pharmacological signaling dissection (H89, 8-Br-cAMP, PMA, ionomycin), PTH(3-34) mutant, in vivo PTH injection Endocrinology Medium 15087429
2014 α1-adrenergic receptor signaling in osteoblasts upregulates Nfil3/E4BP4, which then binds to D-box elements in the Bmp4 promoter (confirmed by ChIP) to repress Bmp4 expression in a circadian manner. ChIP for E4BP4 binding to Bmp4 promoter, α1-AR agonist treatment, gain/loss-of-function for Nfil3, circadian expression analysis Journal of Biological Chemistry Medium 24794868
2019 NFIL3 promotes transcription of REDD1 (binding its promoter) and regulates ferroptosis and inflammation in sepsis-associated acute kidney injury; NFIL3 knockdown attenuates renal tubular ferroptosis and inflammation by downregulating ACSL4. NFIL3 knockdown in vitro and in vivo SA-AKI models, ACSL4 expression analysis, ferroptosis markers Cell Death Discovery Low 39097582
2023 H2S sulfhydrylates NFIL3 protein, which reduces NFIL3 binding to the MEST promoter (confirmed by ChIP-qPCR and luciferase assay) and thereby suppresses MEST transcription, inhibiting low-shear-stress-induced endothelial-mesenchymal transition and atherosclerosis. ChIP-qPCR, luciferase reporter assay, NFIL3 knockdown, H2S donor treatment, sulfhydrylation assay Nitric Oxide Medium 38049061

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development. Nature immunology 364 19749763
2017 The intestinal microbiota regulates body composition through NFIL3 and the circadian clock. Science (New York, N.Y.) 357 28860383
2001 Antagonistic role of E4BP4 and PAR proteins in the circadian oscillatory mechanism. Genes & development 332 11316793
2009 Nfil3/E4bp4 is required for the development and maturation of NK cells in vivo. The Journal of experimental medicine 281 19995955
2014 Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens. The Journal of experimental medicine 218 25113970
2014 Nfil3 is required for the development of all innate lymphoid cell subsets. The Journal of experimental medicine 208 25092873
2014 The basic leucine zipper transcription factor NFIL3 directs the development of a common innate lymphoid cell precursor. eLife 207 25310240
2015 An IL-27/NFIL3 signalling axis drives Tim-3 and IL-10 expression and T-cell dysfunction. Nature communications 181 25614966
2011 The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4+ T cells. Nature immunology 170 21460847
2017 Smad3 promotes cancer progression by inhibiting E4BP4-mediated NK cell development. Nature communications 160 28262747
2014 The transcription factor E4bp4/Nfil3 controls commitment to the NK lineage and directly regulates Eomes and Id2 expression. The Journal of experimental medicine 159 24663216
2015 NFIL3 orchestrates the emergence of common helper innate lymphoid cell precursors. Cell reports 156 25801035
2014 Cutting edge: Salivary gland NK cells develop independently of Nfil3 in steady-state. Journal of immunology (Baltimore, Md. : 1950) 152 24740507
2011 NFIL3/E4BP4 is a key transcription factor for CD8α⁺ dendritic cell development. Blood 147 21474667
2009 IL-4-induced transcription factor NFIL3/E4BP4 controls IgE class switching. Proceedings of the National Academy of Sciences of the United States of America 139 20080759
1997 Pivotal role for the NFIL3/E4BP4 transcription factor in interleukin 3-mediated survival of pro-B lymphocytes. Proceedings of the National Academy of Sciences of the United States of America 127 9122243
2002 E4BP4/NFIL3, a PAR-related bZIP factor with many roles. BioEssays : news and reviews in molecular, cellular and developmental biology 121 12386933
2013 Nfil3-independent lineage maintenance and antiviral response of natural killer cells. The Journal of experimental medicine 119 24277151
1995 Molecular cloning and characterization of NF-IL3A, a transcriptional activator of the human interleukin-3 promoter. Molecular and cellular biology 116 7565758
2014 Differential requirement for Nfil3 during NK cell development. Journal of immunology (Baltimore, Md. : 1950) 106 24532575
2019 An Nfil3-Zeb2-Id2 pathway imposes Irf8 enhancer switching during cDC1 development. Nature immunology 97 31406377
2013 CD8α+ DCs can be induced in the absence of transcription factors Id2, Nfil3, and Batf3. Blood 94 23297132
2011 NFIL3 is a regulator of IL-12 p40 in macrophages and mucosal immunity. Journal of immunology (Baltimore, Md. : 1950) 93 21383239
2010 Transcriptional repressor E4-binding protein 4 (E4BP4) regulates metabolic hormone fibroblast growth factor 21 (FGF21) during circadian cycles and feeding. The Journal of biological chemistry 93 20851878
2006 A novel E4BP4 element drives circadian expression of mPeriod2. Nucleic acids research 87 17182630
2011 E4BP4: an unexpected player in the immune response. Trends in immunology 86 22075207
2015 PDK1 orchestrates early NK cell development through induction of E4BP4 expression and maintenance of IL-15 responsiveness. The Journal of experimental medicine 84 25624444
2011 NFIL3/E4BP4 controls type 2 T helper cell cytokine expression. The EMBO journal 84 21499227
1994 Transcriptional repression by the human bZIP factor E4BP4: definition of a minimal repression domain. Nucleic acids research 81 8127655
1999 Two distinct interleukin-3-mediated signal pathways, Ras-NFIL3 (E4BP4) and Bcl-xL, regulate the survival of murine pro-B lymphocytes. Molecular and cellular biology 73 10082541
2021 Circadian REV-ERBs repress E4bp4 to activate NAMPT-dependent NAD+ biosynthesis and sustain cardiac function. Nature cardiovascular research 59 35036997
2011 A distal enhancer in Il12b is the target of transcriptional repression by the STAT3 pathway and requires the basic leucine zipper (B-ZIP) protein NFIL3. The Journal of biological chemistry 59 21566115
2011 Cellular DBP and E4BP4 proteins are critical for determining the period length of the circadian oscillator. FEBS letters 58 21635892
2022 Elevated expression of the rhythm gene NFIL3 promotes the progression of TNBC by activating NF-κB signaling through suppression of NFKBIA transcription. Journal of experimental & clinical cancer research : CR 51 35180863
2019 The transcription factor NFIL3 controls regulatory T-cell function and stability. Experimental & molecular medicine 51 31311918
2014 The transcription factor E4BP4 is not required for extramedullary pathways of NK cell development. Journal of immunology (Baltimore, Md. : 1950) 49 24534532
2000 Identification of multiple transcription factors, HLF, FTF, and E4BP4, controlling hepatitis B virus enhancer II. Journal of virology 49 10627534
2020 E4BP4-mediated inhibition of T follicular helper cell differentiation is compromised in autoimmune diseases. The Journal of clinical investigation 47 32191636
2004 The CES-2-related transcription factor E4BP4 is an intrinsic regulator of motoneuron growth and survival. Development (Cambridge, England) 43 15306565
2016 Eosinophil resistance to glucocorticoid-induced apoptosis is mediated by the transcription factor NFIL3. Apoptosis : an international journal on programmed cell death 42 26880402
2018 E4BP4 promotes thyroid cancer proliferation by modulating iron homeostasis through repression of hepcidin. Cell death & disease 41 30250199
2013 E4BP4 overexpression: a protective mechanism in CD4+ T cells from SLE patients. Journal of autoimmunity 41 23340290
2007 The negative transcription factor E4BP4 is associated with circadian clock protein PERIOD2. Biochemical and biophysical research communications 41 17274955
2014 NFIL3-deficient mice develop microbiota-dependent, IL-12/23-driven spontaneous colitis. Journal of immunology (Baltimore, Md. : 1950) 40 24442434
1997 Inducibility of E4BP4 suggests a novel mechanism of negative gene regulation by glucocorticoids. Biochemical and biophysical research communications 39 9125190
2019 Cellular prion protein transcriptionally regulated by NFIL3 enhances lung cancer cell lamellipodium formation and migration through JNK signaling. Oncogene 37 31477838
2004 Negative control of circadian clock regulator E4BP4 by casein kinase Iepsilon-mediated phosphorylation. Current biology : CB 37 15182670
2020 LncRNA GAS5 suppresses CD4+ T cell activation by upregulating E4BP4 via inhibiting miR-92a-3p in systemic lupus erythematosus. Immunology letters 36 32781006
2014 New Frontiers for the NFIL3 bZIP Transcription Factor in Cancer, Metabolism and Beyond. Discoveries (Craiova, Romania) 35 26539561
1996 Protein-protein interaction between the transcriptional repressor E4BP4 and the TBP-binding protein Dr1. Nucleic acids research 35 8836190
2016 NFIL3 Expression Distinguishes Tissue-Resident NK Cells and Conventional NK-like Cells in the Mouse Submandibular Glands. Journal of immunology (Baltimore, Md. : 1950) 34 27521341
2013 Recruitment of histone methyltransferase G9a mediates transcriptional repression of Fgf21 gene by E4BP4 protein. The Journal of biological chemistry 34 23283977
2010 Multiple PAR and E4BP4 bZIP transcription factors in zebrafish: diverse spatial and temporal expression patterns. Chronobiology international 34 20854132
1999 Transcriptional repression of human hepatitis B virus genes by a bZIP family member, E4BP4. Journal of virology 32 10074173
2018 The STAT3/NFIL3 signaling axis-mediated chemotherapy resistance is reversed by Raddeanin A via inducing apoptosis in choriocarcinoma cells. Journal of cellular physiology 31 29215740
2008 Negative regulation of the osteoblast function in multiple myeloma through the repressor gene E4BP4 activated by malignant plasma cells. Clinical cancer research : an official journal of the American Association for Cancer Research 31 18829486
2021 mTORC1 and mTORC2 coordinate early NK cell development by differentially inducing E4BP4 and T-bet. Cell death and differentiation 30 33462410
2018 E4bp4 regulates carboxylesterase 2 enzymes through repression of the nuclear receptor Rev-erbα in mice. Biochemical pharmacology 29 29653076
2018 miR-203 accelerates apoptosis and inflammation induced by LPS via targeting NFIL3 in cardiomyocytes. Journal of cellular biochemistry 29 30484891
2014 α1-adrenergic receptor signaling in osteoblasts regulates clock genes and bone morphogenetic protein 4 expression through up-regulation of the transcriptional factor nuclear factor IL-3 (Nfil3)/E4 promoter-binding protein 4 (E4BP4). The Journal of biological chemistry 29 24794868
2003 Parathyroid hormone-induced E4BP4/NFIL3 down-regulates transcription in osteoblasts. The Journal of biological chemistry 29 12743120
2002 GATA factors are essential for transcription of the survival gene E4bp4 and the viability response of interleukin-3 in Ba/F3 hematopoietic cells. The Journal of biological chemistry 29 12023274
2022 E4BP4 Coordinates Circadian Control of Cognition in Delirium. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 28 35713240
2018 NFIL3 mutations alter immune homeostasis and sensitise for arthritis pathology. Annals of the rheumatic diseases 28 30552177
2016 The Transcription Factor NFIL3 Is Essential for Normal Placental and Embryonic Development but Not for Uterine Natural Killer (UNK) Cell Differentiation in Mice. Biology of reproduction 28 26985000
2018 Multiple Levels of Control Determine How E4bp4/Nfil3 Regulates NK Cell Development. Journal of immunology (Baltimore, Md. : 1950) 26 29311361
2014 Glucocorticoid induced osteoblast apoptosis by increasing E4BP4 expression via up-regulation of Bim. Calcified tissue international 25 24658772
2014 E4BP4 is a repressor of epigenetically regulated SOSTDC1 expression in breast cancer cells. Cellular oncology (Dordrecht, Netherlands) 25 25338303
1995 Characterization of human E4BP4, a phosphorylated bZIP factor. Biochimica et biophysica acta 25 8547328
2016 E4BP4 is an insulin-induced stabilizer of nuclear SREBP-1c and promotes SREBP-1c-mediated lipogenesis. Journal of lipid research 24 27252523
2015 NFIL3 suppresses hypoxia-induced apoptotic cell death by targeting the insulin-like growth factor 2 receptor. Journal of cellular biochemistry 24 25536374
2024 Ferroptosis and inflammation are modulated by the NFIL3-ACSL4 axis in sepsis associated-acute kidney injury. Cell death discovery 23 39097582
2020 Hepatic E4BP4 induction promotes lipid accumulation by suppressing AMPK signaling in response to chemical or diet-induced ER stress. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 23 32780887
2017 NFIL3 is a negative regulator of hepatic gluconeogenesis. Metabolism: clinical and experimental 23 29132537
2010 E4BP4 is a cardiac survival factor and essential for embryonic heart development. Molecular and cellular biochemistry 23 20186462
2020 Diurnal Rhythmicity Programs of Microbiota and Transcriptional Oscillation of Circadian Regulator, NFIL3. Frontiers in immunology 22 33013924
2022 NFIL3 and its immunoregulatory role in rheumatoid arthritis patients. Frontiers in immunology 21 36439145
2020 PBX1 promotes development of natural killer cells by binding directly to the Nfil3 promoter. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 32190943
2021 Hepatic metabolic regulation by nuclear factor E4BP4. Journal of molecular endocrinology 20 33434146
2014 Molecular cloning and functional characterization of the NFIL3/E4BP4 transcription factor of grass carp, Ctenopharyngodon idella. Developmental and comparative immunology 20 25083807
2013 Nfil3 is a glucocorticoid-regulated gene required for glucocorticoid-induced apoptosis in male murine T cells. Endocrinology 20 23425966
2010 The transcriptional regulator NFIL3 controls IgE production. Transactions of the American Clinical and Climatological Association 20 20697558
2019 The nuclear factor interleukin 3-regulated (NFIL3) transcription factor involved in innate immunity by activating NF-κB pathway in mud crab Scylla paramamosain. Developmental and comparative immunology 19 31319087
2017 Heterogeneous nuclear ribonucleoprotein A1 regulates rhythmic synthesis of mouse Nfil3 protein via IRES-mediated translation. Scientific reports 19 28220845
2011 E4BP4 facilitates glucocorticoid-evoked apoptosis of human leukemic CEM cells via upregulation of Bim. Journal of molecular signaling 19 21975218
2024 OPN-Mediated Crosstalk Between Hepatocyte E4BP4 and Hepatic Stellate Cells Promotes MASH-Associated Liver Fibrosis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 18 39473081
2021 NFIL3 Facilitates Neutrophil Autophagy, Neutrophil Extracellular Trap Formation and Inflammation During Gout via REDD1-Dependent mTOR Inactivation. Frontiers in medicine 18 34660620
2006 Calcium-dependent upregulation of E4BP4 expression correlates with glucocorticoid-evoked apoptosis of human leukemic CEM cells. Biochemical and biophysical research communications 18 16630563
2004 Parathyroid hormone induces E4bp4 messenger ribonucleic acid expression primarily through cyclic adenosine 3',5'-monophosphate signaling in osteoblasts. Endocrinology 18 15087429
2004 Cell type-specific regulation of von Willebrand factor expression by the E4BP4 transcriptional repressor. Blood 18 15498853
2013 Neuroprotective role of the basic leucine zipper transcription factor NFIL3 in models of amyotrophic lateral sclerosis. The Journal of biological chemistry 17 24280221
2007 Ontogeny of melatonin, Per2 and E4bp4 light responsiveness in the chicken embryonic pineal gland. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 17 17996471
2023 High-Fat Diet-Induced DeSUMOylation of E4BP4 Promotes Lipid Droplet Biogenesis and Liver Steatosis in Mice. Diabetes 16 36508222
2019 The transcription factor E4bp4 regulates the expression and activity of Cyp3a11 in mice. Biochemical pharmacology 15 30796914
2018 A minireview of E4BP4/NFIL3 in heart failure. Journal of cellular physiology 13 29856483
2023 Hydrogen sulfide attenuates atherosclerosis induced by low shear stress by sulfhydrylating endothelium NFIL3 to restrain MEST mediated endothelial mesenchymal transformation. Nitric oxide : biology and chemistry 12 38049061
2022 Nuclear factor interleukin 3 (NFIL3) participates in regulation of the NF-κB-mediated inflammation and antioxidant system in Litopenaeus vannamei under ammonia-N stress. Fish & shellfish immunology 12 36403704
2021 NFIL3 deficiency alleviates EAE through regulating different immune cell subsets. Journal of advanced research 12 35777910
2017 E4BP4 mediates glucocorticoid-regulated adipogenesis through COX2. Molecular and cellular endocrinology 12 28416324
2017 The first invertebrate NFIL3 transcription factor with role in immune defense identified from the Hong Kong oyster, Crassostrea hongkongensis. Developmental and comparative immunology 12 28506725

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