Affinage

ZNF384

Zinc finger protein 384 · UniProt Q8TF68

Length
577 aa
Mass
63.2 kDa
Annotated
2026-06-11
84 papers in source corpus 35 papers cited in narrative 35 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

ZNF384 (CIZ/NMP4) is a C2H2 zinc finger transcription factor that recognizes homopolymeric (dA:dT) DNA elements through zinc fingers 2, 3, and 6 binding in the minor groove, and which integrates extracellular and mechanical signals into transcriptional programs governing matrix remodeling, bone anabolism, and inflammation (PMID:10669742, PMID:11867614). It was first identified through its interaction with the SH3 domain of p130(Cas) at focal adhesions, shuttles between cytoplasm and nucleus, and targets its zinc finger domain to nuclear matrix subdomains (PMID:10669742, PMID:10972987); in human cells the p130(Cas) link is indirect, mediated through zyxin (PMID:16510139). Depending on promoter context it can activate (MMP-1/3/7, MMP-13, RANKL, IL-1β, AQP5) or repress (COL1A1) transcription, with its N-terminal transactivation potential masked in the full-length protein and unmasked allosterically upon DNA binding (PMID:11149472, PMID:11867614, PMID:15026307, PMID:22307584, PMID:26378628, PMID:27058007). Across multiple knockout models ZNF384 acts as a brake on bone formation, suppressing BMP-2- and PTH-induced osteoblast anabolism specifically within Prx1-expressing mesenchymal stem/progenitor cells, in part by restraining mechanically induced β-catenin signaling and glycolytic conversion (PMID:15781586, PMID:19189321, PMID:20112285, PMID:30645175, PMID:36321253). Genome-wide it occupies promoters, enhancers, TAD boundaries, and SINE-Alu elements to regulate transcription (PMID:40250193), and it directly drives pro-inflammatory chemokine/cytokine programs during influenza infection (PMID:32152414). Independently of transcription, ZNF384 functions as a 'Ku-adaptor' in DNA double-strand break repair: after PARP1-dependent chromatin expansion it binds exposed DNA ends through its C2H2 motifs and recruits Ku70/Ku80 via its N-terminus to promote classical non-homologous end-joining (PMID:34772923). Recurrent oncogenic fusions of ZNF384 with transcriptional coactivators (EP300, TCF3, EWSR1, TAF15, SYNRG) transform cells via the zinc finger DNA-binding module, bind EP300 with increased affinity, and deregulate hematopoietic stem cell programs and enhancers — directly activating an intergenic FLT3 enhancer and the IL3RA/CD123 promoter — to drive lineage-ambiguous B/myeloid leukemia (PMID:15669012, PMID:31234226, PMID:35247902, PMID:36104354, PMID:38566191).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2000 High

    Established ZNF384 as a sequence-specific DNA-binding protein that couples focal adhesion signaling to transcription, answering what kind of molecule it is and what it does.

    Evidence Far-Western screen against p130(Cas) SH3, CAST/SELEX, heterokaryon shuttling assay, and promoter-reporter assays for MMP-1/3/7

    PMID:10669742

    Open questions at the time
    • Direct vs. indirect nature of the p130(Cas) interaction not resolved in human cells
    • No structural basis for DNA recognition
  2. 2000 Medium

    Mapped the determinant of nuclear localization, showing the zinc finger domain is necessary and sufficient for nuclear import and matrix targeting.

    Evidence GFP-fusion immunofluorescence with domain deletions in osteoblasts

    PMID:10972987

    Open questions at the time
    • Import receptors/NLS sequence not identified
    • Functional consequence of matrix subdomain targeting unclear
  3. 2001 High

    Showed ZNF384 can act as a transcriptional repressor as well as activator, establishing context-dependent regulation of COL1A1 via poly(dT) binding and DNA bending.

    Evidence Expression-library screening, promoter mutagenesis, antibody disruption and overexpression in UMR-106 osteoblasts

    PMID:11149472

    Open questions at the time
    • Determinants that switch ZNF384 between activation and repression not defined
  4. 2002 High

    Defined the molecular logic of DNA recognition and activation — fingers 2/3/6 bind the minor groove and DNA binding allosterically unmasks the otherwise repressed N-terminal/poly(QA) transactivation function.

    Evidence GAL4 fusion transactivation, zinc-finger deletion mutagenesis, in vitro DNA binding and reporter assays

    PMID:11867614

    Open questions at the time
    • Structural model of the allosteric activation not available
    • Cofactors recruited by the unmasked activation domain unknown
  5. 2002 Medium

    First linked ZNF384 to leukemia via EWSR1 and TAF15 fusions, showing they transform cells independently of normal target-gene regulation.

    Evidence RT-PCR cloning of fusion transcripts and NIH3T3 focus formation with target gene expression analysis

    PMID:12359745

    Open questions at the time
    • Mechanism of transformation not yet linked to specific target genes
    • Single transformation assay system
  6. 2005 High

    Established ZNF384 as a physiological suppressor of bone mass acting through inhibition of BMP signaling, defining its in vivo role.

    Evidence CIZ-knockout mouse histomorphometry, BMP-2 calvarial injection, and bone marrow differentiation assays

    PMID:15781586

    Open questions at the time
    • Direct molecular target in the BMP/Smad pathway not defined
    • Whether suppression is transcriptional or via protein interaction unresolved
  7. 2005 High

    Showed the zinc fingers are obligatory for the oncogenic activity of fusions, demonstrating transformation requires ZNF384 DNA binding.

    Evidence Domain-deletion mutagenesis with NIH3T3 focus formation and MMP7 luciferase reporter for TCF3/VP16 fusions

    PMID:15669012

    Open questions at the time
    • Endogenous target genes driving transformation not identified at this stage
  8. 2006 Low

    Revised the interactome for human ZNF384, finding zyxin (not direct p130CAS), PCBP1, and vimentin as partners.

    Evidence Yeast two-hybrid screening in human cells

    PMID:16510139

    Open questions at the time
    • Yeast two-hybrid only with no orthogonal validation of the interactions
    • Functional consequence of zyxin/PCBP1/vimentin binding untested
  9. 2010 Medium

    Connected ZNF384 to mechanotransduction, showing it restrains mechanically induced β-catenin and growth-factor signaling in osteoblasts.

    Evidence Nmp4-null osteoblasts under oscillatory fluid shear stress with fractionation, Western blot, and immunofluorescence (also EMSA-based MMP-13 mechanoregulation [#12], unloading models [#13])

    PMID:17301008 PMID:17455210 PMID:20112285

    Open questions at the time
    • Direct mechanism linking ZNF384 to β-catenin nuclear entry unknown
    • Upstream mechanosensor coupling to ZNF384 undefined
  10. 2015 High

    Extended ZNF384 function to inflammation and innate immunity, showing direct activation of pro-inflammatory and chemokine gene programs.

    Evidence ChIP and knockout-mouse phenotyping in K/BxN arthritis and influenza infection models with cytokine/chemokine readouts

    PMID:26378628 PMID:32152414

    Open questions at the time
    • Signals that activate ZNF384 inflammatory targets in vivo not defined
    • Cell-type-specific contributions partially resolved
  11. 2019 High

    Defined cell-type-specific and metabolic mechanisms of bone suppression, localizing ZNF384 function to Prx1+ MSPCs and linking it to glycolysis and collagen output.

    Evidence Conditional knockout mice (Prx1/Bglap/Dmp1 Cre), RNA-seq, metabolic and biomechanical assays with PTH challenge

    PMID:19189321 PMID:26244796 PMID:30645175 PMID:36321253

    Open questions at the time
    • Direct transcriptional targets governing glycolytic switch not pinpointed
    • Mechanism of PTH-response modulation unresolved
  12. 2019 Medium

    Mechanistically explained why fusion oncoproteins are more potent — they bind the EP300 coactivator with increased affinity and hyperactivate target promoters/enhancers.

    Evidence GST pull-down and enhancer/promoter reporter assays for EP300- and SYNRG-ZNF384 fusions

    PMID:31234226

    Open questions at the time
    • Genome-wide chromatin consequences not yet mapped at this stage
  13. 2021 High

    Revealed a transcription-independent role in DNA repair, defining ZNF384 as a Ku-adaptor that bridges DNA ends to the NHEJ machinery.

    Evidence In vitro DNA-end binding, laser microirradiation recruitment, PARP1 inhibition, Co-IP with Ku70/Ku80, domain mapping and NHEJ reporter

    PMID:34772923

    Open questions at the time
    • How transcriptional and repair functions are coordinated/partitioned unknown
    • Whether repair role is altered in fusion-bearing leukemia not tested
  14. 2022 High

    Established the genome-wide oncogenic mechanism: fusion proteins occupy enhancers, increase H3K27ac, deregulate HSC transcription factors, and directly activate a FLT3 enhancer to drive lineage-ambiguous leukemia.

    Evidence ChIP-seq, chromatin conformation capture, viral expression and Ep300::Znf384 knockin mouse, xenografts with FLT3 inhibitor treatment

    PMID:35247902 PMID:36104354

    Open questions at the time
    • Full target-gene network across fusion types not exhaustively defined
    • Determinants of B vs myeloid lineage skewing incomplete
  15. 2024 Medium

    Identified additional direct fusion target genes (IL3RA/CD123, RGS1, CREB5) that confer therapeutically actionable and migration phenotypes.

    Evidence ChIP/ChIP-qPCR, luciferase reporters, shRNA knockdown, STAT5 signaling, migration assays and xenografts across multiple fusion types

    PMID:38566191 PMID:39015025

    Open questions at the time
    • Relative contribution of each target to leukemogenesis not ranked
    • RGS1/CREB5 functional validation limited to migration assays
  16. 2025 Medium

    Showed fusion-partner identity dictates distinct downstream phenotypes (e.g., TCF3 fusion-specific dexamethasone resistance and CCND2 upregulation).

    Evidence Retroviral transduction of BCP-ALL lines, apoptosis assays, flow cytometry, microarray and RT-qPCR; plus genome-wide CRISPRi/ChIP-seq/Hi-C epigenome mapping

    PMID:40250193 PMID:40391410

    Open questions at the time
    • Molecular basis of partner-specific differences not defined
    • Generalizability of K562/GM12878 epigenome findings to leukemia subtypes unclear
  17. 2025 Medium

    Expanded the cytoprotective/disease repertoire, showing ZNF384 activates SESN2-mediated autophagy and Fibulin-1-driven vascular pathways.

    Evidence ChIP/DNA pull-down, luciferase reporters, rescue experiments, ferroptosis markers, and in vivo vascular stiffness models

    PMID:40374019 PMID:41816936

    Open questions at the time
    • Conditions activating these programs physiologically unclear
    • Single-lab findings without independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ZNF384 selects between transcriptional activation, repression, and DNA-end repair functions — and how fusion partners reprogram its genomic targeting — remains mechanistically unresolved.
  • No structural model of DNA recognition or coactivator engagement
  • Coordination between repair and transcription roles unknown
  • Determinants of activation-vs-repression switching undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 6 GO:0060090 molecular adaptor activity 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 2 R-HSA-73894 DNA Repair 1
Partners
COL1A1EP300KU70 (XRCC6)KU80 (XRCC5)P130CAS (BCAR1)PCBP1VIMENTIN (VIM)ZYXIN (ZYX)

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 CIZ (ZNF384) was identified as a novel protein that binds the SH3 domain of p130(Cas) via far-Western screening. CIZ co-localizes at focal adhesions and in the nucleus, and acts as a nucleocytoplasmic shuttling protein (demonstrated by transient interspecies heterokaryon formation assay). CIZ binds DNA with consensus sequence (G/C)AAAAA(A) as determined by cyclic amplification and selection of targets (CAST) analysis, and specifically binds the MMP-1 promoter. Overexpression of CIZ upregulates transcription from MMP-1, MMP-3, and MMP-7 promoters, with transactivation enhanced in the presence of Cas. Far-Western screening, heterokaryon shuttling assay, CAST/SELEX DNA binding consensus, promoter-reporter assays, co-immunoprecipitation Molecular and cellular biology High 10669742
2000 NP/NMP4 (ZNF384) proteins localize to distinct nuclear matrix subdomains in osteoblasts. The zinc finger domain was shown to be both necessary and sufficient for nuclear import and nuclear matrix targeting, as determined by immunofluorescence of GFP-NP/NMP4 fusion proteins. Immunofluorescence microscopy, GFP fusion protein localization, domain deletion analysis Journal of cellular biochemistry Medium 10972987
2001 NP/NMP4/CIZ (ZNF384) binds to poly(dT) sequences (sites A and B) in the rat type I collagen alpha1(I) (COL1A1) promoter and bends the DNA. Mutation of sites A or B increased COL1A1 promoter activity in UMR-106 osteoblast-like cells. Overexpression of specific NMP4 clones repressed COL1A1 promoter activity, demonstrating that NMP4/CIZ functions as a transcriptional repressor of COL1A1. Expression library screening with site B probe, promoter-reporter constructs with site mutations, antibody disruption of DNA-protein complexes, overexpression assays Journal of bone and mineral research High 11149472
2000 Overexpression of CIZ (ZNF384) in MC3T3E1 osteoblast-like cells increased focal adhesion plaque number, reduced cell proliferation, enhanced type I collagen mRNA expression, and upregulated a heterologous promoter driven by a CIZ-consensus binding sequence within the type I collagen gene promoter. Overexpression, promoter-reporter assay, RT-PCR, immunofluorescence Experimental cell research Medium 11112339
2002 Zinc fingers 2, 3, and 6 of Nmp4 mediate binding to the homopolymeric (dA.dT) COL1A1/MMP DNA consensus element (minor groove binding). The N-terminus has strong transactivation capacity when fused to GAL4 DBD, but this activity is masked in the full-length protein. Upon binding to the homopolymeric (dA.dT) element, native Nmp4 upregulates transcription, and the polyglutamine-alanine (poly(QA)) domain acquires a significant transactivation role, suggesting allosteric activation by DNA binding. GAL4 fusion transactivation assays, deletion mutagenesis of zinc fingers, promoter-reporter assays, in vitro DNA binding The Journal of biological chemistry High 11867614
2002 CIZ/NMP4 (ZNF384) fuses with EWSR1 (via t(12;22)) or TAF15 (via t(12;17)) in acute leukemia. The resulting fusion proteins have transforming properties in NIH3T3 cells (focus formation assay), but do not affect the expression of CIZ target genes (MMP-1, COL1A1), suggesting oncogenic activity independent of normal CIZ transactivation. RT-PCR/cloning of fusion transcripts, NIH3T3 focus formation assay, target gene expression analysis Cancer research Medium 12359745
2004 Nmp4/CIZ (ZNF384) binds an electrophoretically confirmed cis-element within the MMP-13 PTH response region (-119/-110 nt homopolymeric dA:dT). Mutation of this element decreases basal MMP-13 promoter activity but enhances its PTH/PGE2 responsiveness. Overexpression of Nmp4/CIZ enhances basal MMP-13 promoter activity but diminishes hormone-induced induction. EMSA (electrophoretic mobility shift assay), promoter-reporter mutagenesis, overexpression assays in osteoblasts American journal of physiology. Endocrinology and metabolism High 15026307
2004 CIZ/Nmp4 knockout mice show increased spermatogenic cell apoptosis and variable degrees of spermatogenic cell degeneration in seminiferous tubules, resulting in male infertility in some mice. CIZ/Nmp4 co-localizes with Smad1 in the testis, suggesting it modulates BMP signaling in spermatogenesis. Gene knockout (disruption by beta-galactosidase/neomycin insertion in exon 2), histological analysis, TUNEL assay, immunolocalization Genes to cells Medium 15189450
2005 CIZ-deficient mice show increased bone volume and bone formation rates without changes in bone resorption. CIZ deficiency enhances BMP-2-induced osteoblastic differentiation of bone marrow cells, and BMP-2-induced bone formation on calvariae in vivo is enhanced in CIZ-null mice. This establishes that CIZ (ZNF384) suppresses adult bone mass by inhibiting BMP signaling-induced osteoblast activity. CIZ knockout mouse, bone histomorphometry, bone marrow cell cultures (ALP, mineralization), in vivo BMP-2 calvarial injection, mRNA expression analysis The Journal of experimental medicine High 15781586
2005 E2A-CIZ (TCF3-ZNF384) and VP16-CIZ fusion proteins transform NIH3T3 fibroblasts in focus formation assays. Deletion of the zinc fingers of CIZ abolished both DNA-binding and transforming properties of TAF15-CIZ, while deletion of other CIZ domains had no effect. E2A-CIZ and VP16-CIZ transactivate the MMP7 promoter in luciferase assays, indicating transformation involves ZNF384 zinc finger-mediated DNA binding and transactivation. NIH3T3 focus formation assay, domain deletion mutagenesis, luciferase reporter assay Journal of cellular biochemistry High 15669012
2005 The mouse Nmp4/CIZ gene is driven by two adjacent promoters (P1 and P2) that initiate transcription of alternative first exons. Both promoters lack TATA/CCAAT boxes but contain initiator sites and CpG islands. PTH at low doses attenuates P1/P2 activity in osteoblast-like cells. The promoters are autoregulated, and deletion analysis identified positive and negative regulatory regions. Promoter-reporter assays, Northern blot, deletion analysis, PTH treatment Gene Medium 15716059
2006 Human ZNF384 does not interact with p130CAS directly (in contrast to rat CIZ). Instead, yeast two-hybrid screening identified zyxin, PCBP1, and vimentin as ZNF384 binding partners in human cells. Zyxin can interact with p130CAS, suggesting that zyxin mediates an indirect interaction between ZNF384 and p130CAS in human cells. Yeast two-hybrid screening Experimental cell research Low 16510139
2007 Nmp4/CIZ (ZNF384) contributes to fluid shear stress (FSS)-induced MMP-13 transcription. FSS decreased Nmp4/CIZ binding to its cis-element in the MMP-13 PTH response region (measured by EMSA), and mutation of this element abolished FSS-induced MMP-13 promoter activity. FSS also enhanced Nmp4/CIZ promoter activity and induced p130(Cas) nuclear translocation. EMSA, promoter-reporter assay with mutation, fluid shear stress application, RT-qPCR Journal of cellular biochemistry Medium 17455210
2007 CIZ (ZNF384) deficiency blocks unloading-induced reduction in osteoblastic bone formation parameters in vivo. CIZ-deficient mice resist tail suspension-induced bone loss. Bone marrow cell cultures from unloaded CIZ-null mice maintain mineralized nodule formation, which is suppressed in wild-type unloaded mice, demonstrating CIZ acts in mechanosensory signaling in bone. Tail suspension (unloading) model, bone histomorphometry, bone marrow cell cultures, mineralized nodule formation assay Bone Medium 17301008
2008 Yeast two-hybrid screening of Ciz (ZNF384) binding partners revealed that 47% of positive clones encode extracellular matrix proteins, including Col1a1, Col1a2, Fbln2, and Rpsa. In vitro co-immunoprecipitation using in vitro-translated proteins showed direct binding of Ciz-deltaZF (lacking zinc fingers) to C-propeptides of Col1a1 and Col1a2. In vivo co-immunoprecipitation of transfected Ciz and C-propeptide of Col1a1 was confirmed in COS-7 cells. C-propeptides and Ciz co-localize in the nucleus when overexpressed. Yeast two-hybrid, in vitro translation + co-IP, in vivo co-IP (COS-7 cells), co-localization immunofluorescence Biochemical and biophysical research communications Medium 18211825
2009 Nmp4/CIZ knockout mice exhibit a significantly greater PTH-induced acquisition of femoral trabecular bone versus wild-type mice, establishing that Nmp4/CIZ suppresses PTH-mediated anabolic bone formation. The baseline phenotype showed modestly elevated bone mineral density in null mice. Nmp4-knockout mouse, PTH treatment, microCT, DEXA, histomorphometry Journal of cellular physiology Medium 19189321
2010 Nmp4/CIZ (ZNF384) inhibits mechanically induced beta-catenin nuclear translocation in osteoblasts. In Nmp4-null osteoblasts exposed to oscillatory fluid shear stress (OFSS), nuclear translocation of beta-catenin, ERK, Akt, GSK3beta activity, and cyclin D1 expression are all enhanced. OFSS-induced cytoskeletal reorganization and focal adhesion formation are also qualitatively enhanced in Nmp4-null cells. Calvaria-derived osteoblasts from Nmp4-null mice, OFSS mechanical stimulation, nuclear/cytoplasmic fractionation, immunofluorescence, Western blot Journal of cellular physiology Medium 20112285
2012 CIZ/NMP4 (ZNF384) binds the RANKL promoter at an identified consensus site, activates RANKL transcription (luciferase assay), and overexpression of CIZ/NMP4 enhances B16 melanoma cell migration. RANKL treatment enhances CIZ/NMP4 expression, establishing a positive feedback loop. siRNA knockdown of CIZ/NMP4 suppresses B16 cell migration in Transwell assays. Transwell migration assay, siRNA knockdown, overexpression, luciferase reporter assay, RANKL promoter binding Journal of cellular physiology Medium 22307584
2015 CIZ/NMP4 (ZNF384) deficiency in mice suppresses K/BxN serum-induced arthritis severity. CIZ/NMP4 was shown to bind the IL-1β promoter and activate its transcription (established by promoter binding and luciferase assay), and CIZ/NMP4 deficiency reduced arthritis-induced increases in IL-1β, RANKL, and MMP-3 mRNA. CIZ/NMP4 knockout mouse, K/BxN arthritis model, qPCR, histology, promoter binding/luciferase assay Journal of cellular biochemistry Medium 26378628
2015 ChIP-seq analysis of Nmp4 (ZNF384) in MC3T3-E1 preosteoblasts, murine embryonic stem cells, and blood cell lines identified Nmp4 target genes enriched for negative regulators of biosynthetic processes. ChIP-seq/gene ontology analysis and mRNA expression profiling in Nmp4-null vs. wild-type MSPCs suggest Nmp4 suppresses bone anabolism in part by regulating IGF-binding protein expression. ChIP-seq, RNA-seq/expression profiling, microCT, histomorphometry, FACS Molecular endocrinology Medium 26244796
2016 NMP4 (ZNF384) binds two sites in the AQP5 (aquaporin 5) promoter region (at -1370/-1329 nt and -592/-602 nt) as demonstrated by EMSA. NMP4 overexpression increases AQP5 promoter activity (reporter assays with constructs -469 to -1979 nt) and increases AQP5 mRNA by 2.5-fold in HEK293 cells. EMSA, promoter-reporter assay, overexpression, RT-PCR in HEK293 cells DNA and cell biology Medium 27058007
2019 ZNF384 fusion proteins (EP300-ZNF384, SYNRG-ZNF384) exhibit stronger transcriptional activity on SALL4 and ID2 promoters/enhancers than wild-type ZNF384. GST pull-down assay showed ZNF384 fusion proteins bind EP300 (the coactivator) more strongly than wild-type ZNF384. Co-expression of EP300 specifically enhanced transcriptional activities of ZNF384 fusion proteins. GST pull-down, promoter/enhancer-reporter assay (luciferase), EP300 co-expression, transient transfection FEBS letters Medium 31234226
2019 Loss of Nmp4 (ZNF384) in mesenchymal stem/progenitor cells enhances glycolytic conversion during osteogenic differentiation (a key metabolic step in bone anabolism) and increases collagen translation and secretion. RNA-seq of differentiating Nmp4-null MSPCs showed altered expression of >5,000 genes, with elevated matrix gene expression confirmed by biomechanical testing of bone samples. RNA-seq, metabolic assays (glycolysis measurement), collagen secretion assays, biomechanical bone testing, Nmp4-knockout mouse American journal of physiology. Endocrinology and metabolism Medium 30645175
2020 NMP4 (ZNF384) binds to promoters and/or conserved non-coding sequences of chemokine genes (Ccl2, Ccl7, Cxcl1) and pro-inflammatory cytokine genes (Il1b, Il6) in mouse lung epithelial cells and macrophages, as demonstrated by ChIP. NMP4-deficient mice show significantly reduced expression of these genes and reduced recruitment of monocytes/neutrophils to the lungs during influenza A (H1N1) infection, with no effect on viral clearance. Nmp4-knockout mouse, influenza infection model, ChIP, qPCR, flow cytometry Mucosal immunology High 32152414
2021 ZNF384 binds DNA ends in vitro and is recruited to DNA double-strand breaks (DSBs) in vivo. ZNF384 recruitment to DSBs requires PARP1-dependent chromatin expansion, followed by C2H2 zinc finger binding to exposed DNA. ZNF384 interacts with Ku70/Ku80 via its N-terminus (demonstrated by Co-IP), promoting Ku assembly and recruitment of downstream cNHEJ factors (APLF and XRCC4/LIG4) for efficient DSB repair. In vitro DNA-end binding assay, laser microirradiation/live-cell imaging (recruitment to DSBs), PARP1 inhibition, Co-IP (ZNF384–Ku70/Ku80), domain deletion analysis, NHEJ reporter assay Nature communications High 34772923
2022 ZNF384 fusion oncoproteins (FO) occupy a subset of predominantly intragenic/enhancer chromatin regions with increased histone 3 lysine acetylation and deregulate expression of hematopoietic stem cell transcription factors. In mouse and human HSPCs expressing ZNF384 FO, myeloid lineage skewing, hematopoietic expansion, and self-renewal occur. In human HSPCs, ZNF384 FO alone drove B/myeloid leukemia. An Ep300::Znf384 knockin mouse model confirmed these phenotypes. Viral expression in mouse/human HSPCs, Ep300::Znf384 knockin mouse, ChIP-seq (H3K27ac), RNA-seq, xenograft model, FLT3 inhibitor treatment in vivo Blood cancer discovery High 35247902
2022 ZNF384-rearranged ALL exclusively activates an intergenic enhancer element at the FLT3 locus through direct binding of the fusion protein, leading to enhancer-promoter looping and FLT3 overexpression. Downregulation of ZNF384 blunts FLT3 activation and decreases cell sensitivity to the FLT3 inhibitor gilteritinib in vitro. In ZNF384-rearranged xenograft models, gilteritinib shows significant anti-leukemia efficacy in vivo. ChIP-seq, chromatin conformation capture (enhancer-promoter looping), shRNA knockdown of ZNF384, luciferase/reporter assay, xenograft mouse model, gilteritinib treatment in vivo Nature communications High 36104354
2022 ZNF384 transactivates ZEB1 expression as shown by ChIP-qPCR and luciferase reporter assays, inducing EMT-like phenotype and promoting breast cancer metastasis. ZEB1 in turn upregulates ZNF384 expression by repressing miR-485-5p, forming a positive feedback loop. ChIP-qPCR, luciferase reporter assay, Transwell/scratch migration assays, xenograft mouse model Molecular medicine Medium 36100877
2022 Conditional loss of Nmp4 (ZNF384) from Prx1-expressing mesenchymal stem/progenitor cells phenocopies the enhanced PTH-induced trabecular bone increase seen in global Nmp4-null mice. Conditional deletion in mature osteoblasts (BglapCre) failed to increase bone volume or PTH response. Conditional disabling in osteocytes (Dmp1Cre) increased BV/TV without boosting PTH response, defining Prx1-expressing MSPCs as the key cell type for Nmp4-mediated suppression of bone anabolism. Conditional knockout mice (Prx1Cre, BglapCre, Dmp1Cre × Nmp4-floxed), PTH treatment, microCT, histomorphometry, DEXA Journal of bone and mineral research High 36321253
2024 EP300-ZNF384 fusion protein transactivates the IL3RA (CD123) promoter by directly binding an A-rich sequence at -222/-234 of the IL3RA promoter, as confirmed by ChIP and luciferase reporter assays. EP300-ZNF384-positive B-ALL cells show elevated membrane CD123 and IL-3-stimulated STAT5 activation; knockdown of IL3RA impaired leukemia cell proliferation in vitro and in vivo. ChIP, luciferase reporter assay, shRNA knockdown of IL3RA, in vitro proliferation assay, in vivo xenograft, STAT5 phosphorylation (Western blot) Cell communication and signaling High 38566191
2024 RGS1 and CREB5 are identified as direct and common transcriptional target genes of ZNF384 fusion proteins across multiple fusion types. ChIP-qPCR confirmed binding of ZNF384 fusion proteins to regulatory regions of RGS1 and CREB5. ZNF384 fusion-expressing transfectants showed impaired migration toward CXCL12, consistent with RGS1 (an inhibitor of CXCL12-CXCR4 signaling) being upregulated. RNA-seq of transfectants and clinical ALL samples, ChIP-qPCR, CXCL12 migration assay Cancer medicine Medium 39015025
2025 ZNF384 (ZNF384) was identified as a regulator of the leukemia epigenome. ChIP-seq data show ZNF384 associates with promoters and enhancers in K562 and GM12878 cells, facilitating increased transcription. ZNF384 is enriched at topologically associating domain (TAD) boundaries and chromatin loops (from Hi-C data). ZNF384 shows significant binding at SINE-Alu elements. CRISPRi knockdown of ZNF384 in K562 cells validated transcriptional regulation. ChIP-seq, RNA-seq, Hi-C chromatin conformation data, CRISPRi knockdown Leukemia research Medium 40250193
2025 TCF3::ZNF384 (but not EP300::ZNF384) fusion protein expression in BCP-ALL cell lines confers resistance to dexamethasone-induced apoptosis and significantly upregulates CCND2 (cyclin D2) expression, as shown by oligonucleotide microarray and RT-qPCR. Both fusion proteins downregulate CD10 surface expression. These effects are fusion-partner-dependent. Retrovirus-mediated transduction of BCP-ALL cell lines, annexin-V apoptosis assay, flow cytometry (CD10), oligonucleotide microarray, RT-qPCR Pediatrics international Medium 40391410
2025 ZNF384 functions as a transcriptional activator of SESN2, as confirmed by ChIP and luciferase reporter assays. In LPS-stimulated lung epithelial cells (BEAS-2B), ZNF384 overexpression reduces ferroptosis and inflammation by activating SESN2-mediated autophagy. Depletion of SESN2 reversed these protective effects. ChIP, luciferase reporter assay, overexpression, siRNA knockdown, ferroptosis markers (MDA, GSH, ROS, Fe2+), ELISA for cytokines Toxicology in vitro Medium 40374019
2026 ZNF384 acts as a transcriptional activator of Fibulin-1 (Fbln1) in vascular smooth muscle cells, as identified by DNA pull-down assay and dual-luciferase reporter assay. ZNF384-driven Fbln1 promotes VSMC senescence and collagen deposition through the TGF-β/Smad3 pathway. Fbln1 knockdown ameliorates vascular stiffness in aging and Ang II-infusion mouse models. DNA pull-down assay, dual-luciferase reporter assay, RNA-seq, Fbln1 knockout mouse, Ang II infusion model, pulse wave velocity, histology FASEB journal Medium 41816936

Source papers

Stage 0 corpus · 84 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype. Haematologica 183 27634205
2000 CIZ, a zinc finger protein that interacts with p130(cas) and activates the expression of matrix metalloproteinases. Molecular and cellular biology 115 10669742
2002 Recurrent rearrangement of the Ewing's sarcoma gene, EWSR1, or its homologue, TAF15, with the transcription factor CIZ/NMP4 in acute leukemia. Cancer research 100 12359745
2018 Myeloid lineage switch following chimeric antigen receptor T-cell therapy in a patient with TCF3-ZNF384 fusion-positive B-lymphoblastic leukemia. Pediatric blood & cancer 81 29797659
2005 The nucleocytoplasmic shuttling protein CIZ reduces adult bone mass by inhibiting bone morphogenetic protein-induced bone formation. The Journal of experimental medicine 58 15781586
2001 Cloning and functional analysis of a family of nuclear matrix transcription factors (NP/NMP4) that regulate type I collagen expression in osteoblasts. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 58 11149472
2016 Frequency and outcome of pediatric acute lymphoblastic leukemia with ZNF384 gene rearrangements including a novel translocation resulting in an ARID1B/ZNF384 gene fusion. Pediatric blood & cancer 54 27392123
2021 Zinc finger protein ZNF384 is an adaptor of Ku to DNA during classical non-homologous end-joining. Nature communications 41 34772923
2004 Nmp4/CIZ regulation of matrix metalloproteinase 13 (MMP-13) response to parathyroid hormone in osteoblasts. American journal of physiology. Endocrinology and metabolism 36 15026307
2008 E2A-ZNF384 and NOL1-E2A fusion created by a cryptic t(12;19)(p13.3; p13.3) in acute leukemia. Leukemia 33 18185522
2004 Impaired spermatogenesis and male fertility defects in CIZ/Nmp4-disrupted mice. Genes to cells : devoted to molecular & cellular mechanisms 30 15189450
2011 Identification of the TAF15-ZNF384 fusion gene in two new cases of acute lymphoblastic leukemia with a t(12;17)(p13;q12). Cancer genetics 29 21504714
2006 Interaction partners for human ZNF384/CIZ/NMP4--zyxin as a mediator for p130CAS signaling? Experimental cell research 29 16510139
2022 ZNF384: A Potential Therapeutic Target for Psoriasis and Alzheimer's Disease Through Inflammation and Metabolism. Frontiers in immunology 28 35669784
2009 Nmp4/CIZ suppresses parathyroid hormone-induced increases in trabecular bone. Journal of cellular physiology 28 19189321
2022 ZNF384 Fusion Oncoproteins Drive Lineage Aberrancy in Acute Leukemia. Blood cancer discovery 27 35247902
2001 Involvement of the nuclear matrix in the control of skeletal genes: the NMP1 (YY1), NMP2 (Cbfa1), and NMP4 (Nmp4/CIZ) transcription factors. Critical reviews in eukaryotic gene expression 27 12067068
2002 DNA binding and gene activation properties of the Nmp4 nuclear matrix transcription factors. The Journal of biological chemistry 26 11867614
2000 NP/NMP4 transcription factors have distinct osteoblast nuclear matrix subdomains. Journal of cellular biochemistry 24 10972987
2022 Epigenetic activation of the FLT3 gene by ZNF384 fusion confers a therapeutic susceptibility in acute lymphoblastic leukemia. Nature communications 20 36104354
2000 Overexpression of Cas-interacting zinc finger protein (CIZ) suppresses proliferation and enhances expression of type I collagen gene in osteoblast-like MC3T3E1 cells. Experimental cell research 20 11112339
2023 ZNF384-Related Fusion Genes in Acute Lymphoblastic Leukemia. Cancer control : journal of the Moffitt Cancer Center 19 37306722
2021 A novel class of ZNF384 aberrations in acute leukemia. Blood advances 19 34529760
2007 Nmp4/CIZ contributes to fluid shear stress induced MMP-13 gene induction in osteoblasts. Journal of cellular biochemistry 19 17455210
2022 ZNF384-ZEB1 feedback loop regulates breast cancer metastasis. Molecular medicine (Cambridge, Mass.) 18 36100877
2010 Nmp4/CIZ inhibits mechanically induced beta-catenin signaling activity in osteoblasts. Journal of cellular physiology 18 20112285
2007 Deficiency of CIZ, a nucleocytoplasmic shuttling protein, prevents unloading-induced bone loss through the enhancement of osteoblastic bone formation in vivo. Bone 18 17301008
2019 Loss of Nmp4 optimizes osteogenic metabolism and secretion to enhance bone quality. American journal of physiology. Endocrinology and metabolism 17 30645175
2012 Nmp4/CIZ suppresses the parathyroid hormone anabolic window by restricting mesenchymal stem cell and osteoprogenitor frequency. Stem cells and development 17 22873745
2011 Nmp4/CIZ suppresses the response of bone to anabolic parathyroid hormone by regulating both osteoblasts and osteoclasts. Calcified tissue international 17 21607813
2012 Immortalization and characterization of osteoblast cell lines generated from wild-type and Nmp4-null mouse bone marrow stromal cells using murine telomerase reverse transcriptase (mTERT). Journal of cellular physiology 15 21732358
2019 ZNF384-fusion proteins have high affinity for the transcriptional coactivator EP300 and aberrant transcriptional activities. FEBS letters 14 31234226
2015 Genome-Wide Mapping and Interrogation of the Nmp4 Antianabolic Bone Axis. Molecular endocrinology (Baltimore, Md.) 14 26244796
2009 Nmp4/CIZ: road block at the intersection of PTH and load. Bone 13 19766748
2022 Conditional Loss of Nmp4 in Mesenchymal Stem Progenitor Cells Enhances PTH-Induced Bone Formation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 12 36321253
2015 Mice Deficient in CIZ/NMP4 Develop an Attenuated Form of K/BxN-Serum Induced Arthritis. Journal of cellular biochemistry 12 26378628
2005 Cellular transformation of NIH3T3 fibroblasts by CIZ/NMP4 fusions. Journal of cellular biochemistry 12 15669012
2020 NMP4 regulates the innate immune response to influenza A virus infection. Mucosal immunology 11 32152414
2021 Leukemia With TCF3-ZNF384 Rearrangement as a Distinct Subtype of Disease With Distinct Treatments: Perspectives From A Case Report and Literature Review. Frontiers in oncology 10 34395283
2020 Detection of EP300-ZNF384 fusion in patients with acute lymphoblastic leukemia using RNA fusion gene panel sequencing. Annals of hematology 10 32980888
2016 Mixed Phenotype Acute Leukemia with t(12;17)(p13;q21)/TAF15-ZNF384 and Other Chromosome Abnormalities. Cytogenetic and genome research 10 27607436
2015 Establishment and genetic characterization of a novel mixed-phenotype acute leukemia cell line with EP300-ZNF384 fusion. Journal of hematology & oncology 10 26293203
2022 Zinc finger protein 384 (ZNF384) impact on childhood mixed phenotype acute leukemia and B-cell precursor acute lymphoblastic leukemia. Leukemia & lymphoma 9 35921545
2012 CIZ/NMP4 is expressed in B16 melanoma and forms a positive feedback loop with RANKL to promote migration of the melanoma cells. Journal of cellular physiology 9 22307584
2005 Two promoters control the mouse Nmp4/CIZ transcription factor gene. Gene 9 15716059
2021 Systematic application of fluorescence in situ hybridization and immunophenotype profile for the identification of ZNF384 gene rearrangements in B cell acute lymphoblastic leukemia. International journal of laboratory hematology 8 33988307
2018 An Adult Patient with Early Pre-B Acute Lymphoblastic Leukemia with t(12;17)(p13;q21)/ZNF384-TAF15. In vivo (Athens, Greece) 8 30150451
2024 EP300-ZNF384 transactivates IL3RA to promote the progression of B-cell acute lymphoblastic leukemia. Cell communication and signaling : CCS 7 38566191
2023 A Transcription Factor ZNF384, Regulated by LINC00265, Activates the Expression of IFI30 to Stimulate Malignant Progression in Glioma. ACS chemical neuroscience 7 38141017
2016 The Transcription Factor NMP4 Binds to the AQP5 Promoter and Is a Novel Transcriptional Regulator of the AQP5 Gene. DNA and cell biology 7 27058007
2002 Osteoblast intracellular localization of Nmp4 proteins. Bone 7 12052465
2008 Ciz, a transcription factor with a nucleocytoplasmic shuttling activity, interacts with C-propeptides of type I collagen. Biochemical and biophysical research communications 6 18211825
2024 METTL3-mediated m6A modification of ZNF384 promotes hepatocellular carcinoma progression by transcriptionally activating ACSM1. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 5 39342516
2024 The pivotal role of ZNF384: driving the malignant behavior of serous ovarian cancer cells via the LIN28B/UBD axis. Cell biology and toxicology 5 39562372
2023 Loss of Nmp4 enhances bone gain from sclerostin antibody administration. Bone 5 37660938
2021 Nmp4, a Regulator of Induced Osteoanabolism, Also Influences Insulin Secretion and Sensitivity. Calcified tissue international 5 34417862
2012 Nmp4/CIZ closes the parathyroid hormone anabolic window. Critical reviews in eukaryotic gene expression 5 23140162
2024 ZNF384 fusion transcript levels for measurable residual disease monitoring in adult B-cell acute lymphoblastic leukemia. Hematological oncology 4 38287528
2023 NMP4, an Arbiter of Bone Cell Secretory Capacity and Regulator of Skeletal Response to PTH Therapy. Calcified tissue international 4 37147466
2022 Immunophenotypic characteristics of ZNF384 rearrangement compared with BCR-ABL1, KMT2A rearrangement, and other adult B-cell precursor acute lymphoblastic leukemia. Cytometry. Part B, Clinical cytometry 4 35735203
2016 Low BIK outside-inside-out interactive inflammation immune-induced transcription-dependent apoptosis through FUT3-PMM2-SQSTM1-SFN-ZNF384. Immunologic research 4 26423071
2009 TAF15 and the leukemia-associated fusion protein TAF15-CIZ/NMP4 are cleaved by caspases-3 and -7. Biochemical and biophysical research communications 4 19426707
2025 ZNF384 mediates KRT23 to promote CRC process through the TGF-β/Smad signaling pathway. Cytotechnology 3 40453923
2024 ZNF384 transcriptionally activated MGST1 to confer TMZ resistance of glioma cells by negatively regulating ferroptosis. Cancer chemotherapy and pharmacology 3 38824270
2022 Whole transcriptome sequencing reveals a TCF4-ZNF384 fusion in acute lymphoblastic leukemia. Frontiers in oncology 3 36052266
2021 Detection of a Cryptic EP300/ZNF384 Gene Fusion by Chromosomal Microarray and Next-Generation Sequencing Studies in a Pediatric Patient with B-Lymphoblastic Leukemia. Laboratory medicine 3 33145596
2021 MRD-Negative Remission Induced in EP300-ZNF384 Positive B-ALL Patients by Tandem CD19/CD22 CAR T-Cell Therapy Bridging to Allogeneic Stem Cell Transplantation. OncoTargets and therapy 3 34744437
2025 Identification of ZNF384 as a regulator of epigenome in leukemia. Leukemia research 2 40250193
2024 RGS1 and CREB5 are direct and common transcriptional targets of ZNF384-fusion proteins. Cancer medicine 2 39015025
2025 TCF3::ZNF384 induces steroid resistance in B-cell precursor acute lymphoblastic leukemia cells. Pediatrics international : official journal of the Japan Pediatric Society 1 40391410
2025 TAF15::ZNF384 Mixed Phenotype Acute Leukemia With Complex Karyotype: Case Report With B-ALL Induction, Blinatumomab Bridging to Allogeneic Transplant and Literature Review. Clinical case reports 1 41158816
2024 Clinicopathological and Immunophenotypic Characteristics of Series of ZNF384 Re-arranged Acute Leukemias. Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 1 39469177
2024 Mixed-phenotype leukemia with TCF3::ZNF384 fusion presenting as an isolated mediastinal mass. Annals of hematology 1 39531055
2020 [Analysis of Clinical Characteristics of Acute B Lymphoblastic Leukemia with EP300-ZNF384 Fusion Gene Positive]. Zhongguo shi yan xue ye xue za zhi 1 32027248
2026 ZNF384-regulated SLC31A1 expression promotes tumor proliferation and invasion in breast cancer. Molecular and cellular biochemistry 0 41553436
2026 Improvements in bone quality by parathyroid hormone treatment are enhanced in the Nmp4 knockout mouse model. Bone 0 41565170
2026 ZNF384-Driven Fibulin-1 Exacerbates Vascular Stiffness via TGF-β/Smad3-Mediated Senescence and Fibrosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 41816936
2025 ZNF384 and m6A methylation promote the progression of hepatocellular carcinoma by regulating the interaction between LINC00342 and DAPK1. Cellular signalling 0 39961407
2025 Zinc finger transcription factor ZNF384 mitigates LPS-induced ferroptosis and inflammation in lung epithelial cells by activating SESN2-mediated autophagy. Toxicology in vitro : an international journal published in association with BIBRA 0 40374019
2025 [Clinical features of acute B lymphoblastic leukemia with TAF15::ZNF384 fusion gene]. Zhonghua yi xue za zhi 0 40873094
2025 Unveiling the ZNF384-INTS13-hnRNPC axis as a therapeutic vulnerability in cervical cancer. Cell death & disease 0 41429980
2024 FISH combined with RT-PCR facilitates classification of Chinese adult patients with B-other ALL through improved identification of ZNF384 rearrangement. Leukemia & lymphoma 0 39520726
2023 [Clinical characteristics and outcomes of childhood B-ALL with ZNF384 and MEF2D rearrangements]. [Rinsho ketsueki] The Japanese journal of clinical hematology 0 37544723
2021 [Identification of TCF3-ZNF384 fusion by transcriptome sequencing in B cell acute lymphoblastic leukemia and its laboratory and clinical characteristics]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 33834463

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