Affinage

ZNF217

Zinc finger protein 217 · UniProt O75362

Length
1048 aa
Mass
115.3 kDa
Annotated
2026-06-11
85 papers in source corpus 32 papers cited in narrative 32 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

ZNF217 is a Krüppel-like C2H2 zinc-finger transcription factor that nucleates a chromatin-modifying repressor complex to silence developmental and tumor-suppressor genes while driving cellular immortalization and oncogenic transformation (PMID:9671742, PMID:11245413, PMID:17130829). It recognizes DNA through a non-canonical two-finger unit (zinc fingers 6 and 7) whose side-chain contacts and tyrosine–thymine methyl-π interactions depart from the classical zinc-finger recognition mode (PMID:21908891, PMID:23436653). Once bound, ZNF217 assembles a multi-subunit corepressor complex containing CoREST, LSD1/BHC110, HDAC1/2, and CtBP1/2 — engaging CtBP via both a canonical PXDLS motif and a novel RRT motif — and recruits additional histone modifiers Jarid1b, G9a, and EZH2 to impose H3K4 demethylation, H3K9/H3K27 methylation, and histone deacetylation at target promoters (PMID:17130829, PMID:16940172, PMID:19242095, PMID:30898548, PMID:37648814). Through this complex ZNF217 directly represses tumor suppressors including p15ink4b, E-cadherin (CDH1), and ferroportin, and at the p15ink4b promoter it cooperates with DNMT3A and antagonizes TGF-β-driven SMAD2/3 recruitment and active DNA demethylation (PMID:17130829, PMID:18625718, PMID:22560925, PMID:27768596, PMID:30898548). Beyond repression, ZNF217 activates context-specific targets — ErbB3, Aurora-A, Notch1, MYB, and FOS — sometimes in a CtBP- or CoREST-independent manner, augmenting PI3K/Akt signaling, conferring chemoresistance, and sustaining cancer stem-cell self-renewal (PMID:16203743, PMID:20661224, PMID:21059223, PMID:38134973, PMID:40093906, PMID:40083704). ZNF217 additionally interacts with ERα to enhance estrogen-responsive transcription and with MDM2 to suppress p53-dependent transactivation, and it inhibits METTL3-dependent m6A methylation of pluripotency factor mRNAs (NANOG, KLF4) to promote EMT and breast cancer stem-cell specification (PMID:24973012, PMID:24962896, PMID:27792410, PMID:27590511, PMID:35121826). Collectively these activities drive immortalization, EMT, metastasis, and therapy resistance across multiple cancer types (PMID:11245413, PMID:28207159, PMID:40093906).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1998 Medium

    Establishing ZNF217's molecular identity was the first step: it answered whether the recurrently amplified 20q13.2 locus encoded a defined regulatory protein.

    Evidence Positional cloning and sequence/expression analysis of the 20q13.2 amplicon

    PMID:9671742

    Open questions at the time
    • No DNA targets or interacting partners identified
    • Activation vs repression function undefined
  2. 2001 High

    Demonstrated that ZNF217 is functionally oncogenic, not merely amplified, by showing it immortalizes primary mammary epithelial cells.

    Evidence Retroviral ZNF217 transduction of HMECs with telomerase and TGF-β resistance readouts

    PMID:11245413

    Open questions at the time
    • Transcriptional targets driving immortalization unknown
    • Mechanism of TGF-β resistance unresolved
  3. 2005 High

    Linked ZNF217 to survival signaling, showing it attenuates DNA-damage apoptosis and engages the PI3K/Akt axis, explaining a chemoresistance mechanism.

    Evidence siRNA knockdown and overexpression with apoptosis assays and p-Akt immunoblotting

    PMID:16203743

    Open questions at the time
    • Direct mediators between ZNF217 and Akt not identified
    • Reciprocal regulation of ZNF217 by Akt mechanistically unclear
  4. 2006 High

    Defined ZNF217 as a sequence-specific corepressor by purifying its CoREST/LSD1/HDAC2/CtBP1 complex with H3K4 demethylase and deacetylase activity and identifying its DNA consensus, and resolved how it contacts CtBP.

    Evidence Affinity purification, in vitro enzymatic assays, CAST DNA selection, ChIP; plus CtBP–RRT peptide crystal structure with mutagenesis

    PMID:16940172 PMID:17130829

    Open questions at the time
    • Full target gene repertoire unknown
    • Structural basis of DNA recognition not yet determined
  5. 2007 High

    Established the genome-wide scope of ZNF217 repression, showing it occupies thousands of developmental-gene promoters with CtBP2 and is downregulated during differentiation.

    Evidence ChIP-chip with siRNA knockdown and expression profiling in tumor lines and NTera2 cells

    PMID:17259635

    Open questions at the time
    • Direct vs indirect targets not all distinguished
    • Mechanism linking binding to activation upon removal unclear
  6. 2008 High

    Connected ZNF217 to growth control by identifying p15ink4b as a direct CoREST-complex target whose TGF-β activation requires ZNF217 release, and placed eEF1A2 downstream in transformation.

    Evidence ChIP-DSL, histone-mark ChIP, TGF-β stimulation, and siRNA epistasis with eEF1A2

    PMID:18625718 PMID:18661515

    Open questions at the time
    • How TGF-β triggers ZNF217 eviction not defined
    • eEF1A2 regulation mechanism (direct/indirect) unclear
  7. 2009 High

    Expanded the corepressor complex to include Jarid1b, G9a, and EZH2, establishing that ZNF217 coordinates multiple histone-modifying activities (H3K4 demethylation, H3K9/H3K27 methylation).

    Evidence Affinity chromatography, mass spectrometry, co-IP, and in vitro histone methylation/demethylation assays

    PMID:19242095

    Open questions at the time
    • Stoichiometry and assembly order of subunits unknown
    • Whether all activities act at the same loci unresolved
  8. 2010 Medium

    Showed ZNF217 also functions as a transcriptional activator at specific loci, activating ErbB3 (CtBP-independent) and Aurora-A to drive Akt signaling and paclitaxel resistance.

    Evidence ChIP, gain/loss-of-function, Bcl-2 family immunoblotting, Aurora-A inhibition, and xenografts

    PMID:20661224 PMID:21059223

    Open questions at the time
    • Molecular switch between repression and activation unknown
    • Direct vs indirect activation of Aurora-A unclear
  9. 2011 High

    Resolved the DNA-recognition mechanism, defining a two-finger (ZF6-7) DNA-binding unit and a suboptimal E-cadherin site, establishing ZNF217 as a distinct recognition subclass.

    Evidence NMR analysis, fluorescence anisotropy, and mutagenesis

    PMID:21908891

    Open questions at the time
    • Genome-wide consensus relationship to ZF6-7 specificity incomplete
    • Role of remaining zinc fingers undefined
  10. 2012 High

    Detailed the epigenetic mechanism at p15ink4b, showing the ZNF217/CoREST/DNMT3A complex blocks TGF-β-induced active DNA demethylation by preventing SMAD2/3 and TDG recruitment.

    Evidence ChIP-seq, 5mC/5hmC DNA-IP, TDG/MBD4 siRNA, and TGF-β stimulation

    PMID:22560925

    Open questions at the time
    • Generality of DNMT3A coupling beyond p15ink4b unknown
    • Signal triggering complex displacement not fully defined
  11. 2013 High

    Provided atomic detail of ZNF217–DNA contacts, revealing non-canonical methyl-π (tyrosine–thymine) interactions absent from classical zinc-finger complexes.

    Evidence X-ray crystal structure of ZF6-7–DNA complex

    PMID:23436653

    Open questions at the time
    • Structure of full-length protein on chromatin unknown
    • Link between recognition mode and target selection unresolved
  12. 2014 Medium

    Integrated ZNF217 into estrogen signaling, showing direct ERα interaction and co-occupancy with FOXA1/GATA3/ERα at distal enhancers regulating estrogen-responsive genes.

    Evidence Co-IP in cells/tumors, domain mapping, ChIP-seq, and transcriptome profiling after depletion

    PMID:24962896 PMID:24973012

    Open questions at the time
    • Whether ERα coactivation is corepressor-complex-dependent unclear
    • Single-lab co-IP for ERα–ZNF217 interaction
  13. 2016 Medium

    Broadened ZNF217's regulatory range to RNA m6A, p53, and iron metabolism — inhibiting m6A of NANOG/KLF4 under hypoxia, interacting with MDM2 to suppress p53, and partnering with EZH2 to repress ferroportin.

    Evidence m6A quantification with HIF knockdown; MDM2 affinity-MS and p53/p21 assays; EZH2 co-IP and ferroportin ChIP

    PMID:27590511 PMID:27768596 PMID:27792410 PMID:28607476

    Open questions at the time
    • Direct vs indirect interference with m6A machinery undefined at this stage
    • Physiological balance between these distinct activities unknown
  14. 2019 Medium

    Confirmed in hepatocellular carcinoma that ZNF217 recruits LSD1 to the CDH1 promoter to enforce E-cadherin silencing via H3K4me2 removal.

    Evidence Co-IP in vivo/in vitro, H3K4me2 ChIP, and siRNA knockdown

    PMID:30898548

    Open questions at the time
    • Cell-type generality of LSD1 recruitment to CDH1 unclear
    • Direct ZNF217 binding to CDH1 promoter in this system not structurally validated
  15. 2020 Medium

    Linked ZNF217 to mechanotransduction and metastatic niche signaling — matrix stiffness represses miR-203 to elevate ZNF217 and Akt activity, while ZNF217 activates BMP signaling to promote bone metastasis.

    Evidence miR-203 profiling, Akt assays, mouse mammographic density model; BMP inhibitor rescue and in vivo imaging

    PMID:28207159 PMID:32721948

    Open questions at the time
    • Direct ZNF217 targets in BMP/mechanotransduction pathways not mapped
    • Single-lab in vivo findings
  16. 2022 Medium

    Mechanistically resolved the m6A connection, showing ZNF217 physically interacts with METTL3 to block m6A methylation of NANOG mRNA and promote EMT.

    Evidence Co-IP, MeRIP, PAR-CLIP, dual-luciferase, knockdown, and xenografts

    PMID:35121826

    Open questions at the time
    • Whether ZNF217 directly inhibits METTL3 catalysis or sequesters it unclear
    • Breadth of m6A-regulated transcripts undefined
  17. 2023 High

    Extended ZNF217's repressor function to chromatin accessibility in lymphoma and EBV restriction, and uncovered druggability through covalent cysteine modification by dimethyl fumarate.

    Evidence ATAC-seq and MS-confirmed complex in PMBCL; CRISPR-KO ChIP and 3D chromatin in EBV (preprint); cysteine-directed proteomics with DMF probe

    PMID:37477798 PMID:37648814 PMID:39877093

    Open questions at the time
    • EBV findings from preprint not peer-reviewed
    • DMF target selectivity in cells not fully defined
  18. 2023 Medium

    Established ZNF217 as a transcriptional activator of Notch1 sustaining colorectal cancer stem-cell self-renewal.

    Evidence Dual-luciferase reporter, overexpression, Notch1 knockdown rescue, and sphere/xenograft assays

    PMID:38134973

    Open questions at the time
    • Direct promoter occupancy at Notch1 not confirmed by ChIP
    • Relationship to corepressor complex unclear
  19. 2024 Low

    Proposed a ZNF217/GRHL3/SLC22A31 transcriptional axis driving thyroid cancer malignancy.

    Evidence Lentiviral knockdown and functional rescue without direct promoter-binding confirmation

    PMID:39354204

    Open questions at the time
    • No direct ZNF217 binding to GRHL3 promoter demonstrated
    • Single-lab, single-method-type epistasis
  20. 2025 High

    Defined ZNF217 as essential in leukemia, dissecting CoREST-dependent and -independent oncogenic outputs (FOS repression, MYB activation within a core transcriptional circuit).

    Evidence CRISPR screen, RNA-seq, CUT&RUN/CUT&Tag, reporter assays, and PDX models in B-ALL and AML

    PMID:40083704 PMID:40093906

    Open questions at the time
    • Mechanistic basis of CoREST-independent activity unresolved
    • How a corepressor activates MYB/super-enhancers structurally unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how ZNF217 switches between corepressor and coactivator functions at different loci and how its CoREST-independent oncogenic activities are mechanistically executed.
  • No structural or biochemical model for context-dependent activation
  • Determinants of CoREST-dependent vs -independent function unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 3 GO:0060089 molecular transducer activity 3 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0000228 nuclear chromosome 4 GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-4839726 Chromatin organization 4 R-HSA-1643685 Disease 3 R-HSA-8953854 Metabolism of RNA 2
Partners
CORESTCTBP1ESR1EZH2HDAC1LSD1MDM2METTL3
Complex memberships
ZNF217/CoREST/LSD1/HDAC/CtBP corepressor complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 ZNF217 encodes Krüppel-like transcription factors (1,062 and 1,108 aa) with eight C2H2 zinc fingers and a proline-rich transcription activation domain, and localizes to the nucleus; it was identified by positional cloning of the 20q13.2 amplicon. Positional cloning, sequence analysis, expression analysis Proceedings of the National Academy of Sciences of the United States of America Medium 9671742
2001 ZNF217 overexpression in finite-lifespan human mammary epithelial cells (HMECs) drives immortalization, allowing cells to overcome senescence and acquire telomerase activity, stable telomere length, and resistance to TGF-β growth inhibition. Retroviral transduction of ZNF217 into primary HMECs; telomerase activity assays; TGF-β sensitivity assays Cancer research High 11245413
2005 ZNF217 localizes predominantly to the nucleus and attenuates apoptotic signals from telomere dysfunction and doxorubicin-induced DNA damage; silencing ZNF217 by siRNA restores doxorubicin sensitivity. ZNF217 also increases Akt phosphorylation, and PI3K/Akt pathway inhibition decreases ZNF217 protein levels. siRNA knockdown; ZNF217 overexpression; apoptosis assays; immunoblotting for p-Akt; subcellular fractionation/localization Human molecular genetics High 16203743
2006 ZNF217 is a transcriptional repressor whose purified complex (~6 proteins) contains CoREST, BHC110/LSD1, HDAC2, and CtBP1; the complex possesses histone deacetylase activity and H3K4-specific demethylase activity. ZNF217 binds a specific DNA consensus recognition sequence (CRS) present in the E-cadherin promoter and represses E-cadherin transcription in vivo. Affinity purification of ZNF217 complex; HDAC and H3K4 demethylase in vitro assays; CAST assay for DNA CRS; ChIP; siRNA knockdown with transient transfection reporter assays Oncogene High 17130829
2006 ZNF217 contacts CtBP via two distinct motifs: a canonical PXDLS motif and a novel RRT (Arg-Arg-Thr) motif. The crystal structure of CtBP bound to an RRTGAPPAL peptide shows the RRT motif contacts a surface crevice distinct from the PXDLS-binding cleft. Mutations preventing ZNF217–CtBP contact reduce ZNF217-mediated transcriptional repression. Crystal structure of CtBP–RRT peptide complex; mutagenesis; transcriptional reporter assays Molecular and cellular biology High 16940172
2007 Genome-wide ChIP-chip analysis identified thousands of ZNF217 binding sites in tumor cell lines; many promoters co-bound by ZNF217 and CtBP2 are activated upon ZNF217 removal, confirming ZNF217 functions as a transcriptional repressor. ZNF217 targets are enriched in organ development genes, and ZNF217 is downregulated during retinoic acid-induced differentiation of NTera2 cells. ChIP-chip (chromatin immunoprecipitation with microarray); ZNF217 siRNA knockdown; gene expression profiling The Journal of biological chemistry High 17259635
2008 The p15ink4b tumor suppressor gene is a direct target of the ZNF217/CoREST complex; ZNF217 knockdown in MCF-7 cells dramatically increases p15ink4b expression with increases in H3K4 dimethylation at its promoter. TGF-β stimulation releases ZNF217 from the p15ink4b promoter and allows SMAD2 binding and gene activation. Genome-wide expression profiling combined with ChIP-DSL; siRNA knockdown; ChIP for histone marks; TGF-β stimulation assays Molecular and cellular biology High 18625718
2008 ZNF217 overexpression in immortalized ovarian surface epithelial cells (IOSE) transcriptionally activates eEF1A2, and siRNA to eEF1A2 reverses both eEF1A2-driven and ZNF217-driven anchorage independence and apoptosis resistance, placing eEF1A2 downstream of ZNF217 in a neoplastic transformation pathway. Retroviral ZNF217 overexpression; siRNA knockdown of eEF1A2; array CGH; Affymetrix expression analysis; anchorage independence and apoptosis assays International journal of cancer Medium 18661515
2009 A ZNF217 nuclear complex purified by affinity chromatography contains Jarid1b/Plu-1, G9a, LSD1, CoREST, and CtBP1 (confirmed by co-IP); the complex exhibits H3K4me3 demethylase activity (co-fractionating with Jarid1b), H3K9 methyltransferase activity (via G9a), and H3K27 methylation activity; EZH2 is an additional ZNF217 binding partner confirmed by co-IP. Affinity chromatography; mass spectrometry; co-immunoprecipitation; in vitro histone methylation and demethylation assays; anion-exchange chromatography fractionation Epigenetics High 19242095
2010 ZNF217 activates ErbB3 expression in breast cancer cells; ZNF217 recruitment to the ErbB3 promoter is CtBP1/2-independent, and ZNF217 and CtBP1/2 have opposing roles at the ErbB3 promoter. ErbB3 upregulation is one mechanism by which ZNF217 augments PI3K/Akt signaling. Ectopic ZNF217 expression; siRNA knockdown; ChIP; correlation analysis across 50 breast cancer cell lines and 15 primary tumors Oncogene Medium 20661224
2010 ZNF217 overexpression in MDA-MB-231 cells confers resistance to paclitaxel through deregulation of Bcl-2 family protein balance in the intrinsic apoptotic pathway; ZNF217 overexpression also increases Aurora-A protein expression, and Aurora-A kinase inhibition reverses paclitaxel resistance. Stable ZNF217 overexpression; siRNA knockdown; apoptosis assays; Bcl-2 family immunoblotting; Aurora-A inhibitor treatment; xenograft assays Molecular cancer Medium 21059223
2011 ZNF217 DNA-binding activity is mediated by a two-finger unit (zinc fingers 6 and 7); NMR analysis and mutagenesis define the DNA binding surface, and the E-cadherin promoter site is a suboptimal binding site. Multi-finger proteins with two-finger units represent a distinct subclass of DNA recognition motif. NMR analysis; fluorescence anisotropy titrations; mutagenesis; sequence analysis The Journal of biological chemistry High 21908891
2012 The ZNF217/CoREST complex occupies the p15ink4b promoter together with DNMT3A; TGF-β treatment triggers active DNA demethylation by loss of ZNF217/CoREST/DNMT3A and recruitment of SMAD2/3, CBP, and TDG glycosylase. ZNF217 overexpression prevents TGF-β-dependent demethylation and p15ink4b expression by blocking SMAD2/3 and TDG recruitment; 5mC is converted to 5hmC prior to p15ink4b activation. ChIP and ChIP-seq; DNA immunoprecipitation for 5mC and 5hmC; TDG/MBD4 siRNA knockdown; ZNF217 overexpression; TGF-β stimulation Molecular cell High 22560925
2013 Crystal structure of a ZNF217 two-zinc-finger–DNA complex reveals that the side-chain interaction pattern differs substantially from the canonical ZF model and identifies two methyl-π interactions (tyrosine–thymine methyl) not previously described in classical ZF–DNA complexes. X-ray crystal structure determination of ZNF217 ZF6-7–DNA complex The Journal of biological chemistry High 23436653
2014 ZNF217 and ERα proteins physically interact via the ERα hinge domain and the ZNF217 C-terminal domain (confirmed by co-IP in breast cancer cells and primary tumor samples); ZNF217 enhances ERα recruitment to estrogen response elements and ERα-dependent transcription of GREB1. Co-immunoprecipitation in cell lines and primary tumor samples; domain-mapping experiments; ChIP; transcriptional reporter assays Molecular oncology Medium 24973012
2014 Genome-wide ChIP-seq in MCF7 cells shows ZNF217 binding sites are enriched at distal regulatory regions marked by H3K27ac and H3K4me1, clustering with FOXA1, GATA3, and ERα binding sites; ERα co-precipitates ZNF217 and CtBP2 from nuclear extracts; ZNF217 depletion alters expression of genes co-bound by ZNF217 and ERα. ChIP-seq; co-immunoprecipitation; transcriptome profiling after ZNF217 siRNA depletion; bioinformatic motif enrichment analysis BMC genomics Medium 24962896
2016 ZNF217 inhibits m6A methylation of NANOG and KLF4 mRNAs under hypoxia in breast cancer cells, promoting BCSC specification; this ZNF217-dependent inhibition of m6A methylation is HIF-dependent and occurs independently of or in parallel with ALKBH5-mediated demethylation. ZNF217 knockdown; m6A quantification; HIF knockdown; pluripotency factor expression assays; in vivo metastasis assay Oncotarget Medium 27590511
2016 ZNF217 positively regulates E2 (estradiol) synthesis in granulosa cells by promoting CREB and thereby CYP19A1 (aromatase) expression; ZNF217 also negatively regulates TSP-1 expression, modulating vascular permeability through downstream claudin-1 and NO. In vitro KGN cell overexpression and knockdown of ZNF217; E2 assays; RT-qPCR for CYP19A1, CREB, TSP-1; vascular cell functional assays Scientific reports Medium 28607476
2016 ZNF217 interacts with MDM2; when co-expressed, ZNF217 and MDM2 form a complex and ZNF217 reduces acetylated p53 levels and suppresses p53-dependent p21 promoter activation, in part through recruitment of HDAC1. MDM2 affinity chromatography; mass spectrometry identification of ZNF217; co-expression in cancer cells; p53 acetylation immunoblotting; p21 promoter reporter assays Biochemistry and cell biology Medium 27792410
2016 ZNF217 interacts with EZH2 to facilitate H3K27me3 at the ferroportin (FPN) promoter, repressing FPN transcription and retaining intracellular iron; MAZ transcription factor activates ZNF217 transcription and this axis regulates iron metabolism in prostate cancer cells. Co-immunoprecipitation of ZNF217 and EZH2; ChIP for H3K27me3 at FPN promoter; siRNA knockdown; overexpression assays; iron and cell growth assays Oncotarget Medium 27768596
2017 ZNF217 overexpression in breast cancer cells activates the BMP signaling pathway, contributing to bone metastasis; BMP pathway inhibition (Noggin, LDN-193189) rescues ZNF217-dependent cell migration, invasion, and chemotaxis toward bone environment. ZNF217 increases metastatic growth rate and osteolytic lesions in vivo. Stable ZNF217 transfection; in vitro migration/invasion/chemotaxis assays; BMP inhibitor treatment; in vivo multimodal imaging in mouse models The Journal of pathology Medium 28207159
2019 ZNF217 physically interacts with LSD1 in vivo and in vitro; ZNF217 knockdown increases H3K4me2 at the CDH1 (E-cadherin) promoter, indicating ZNF217 recruits LSD1 to epigenetically repress CDH1 transcription in hepatocellular carcinoma cells. Co-immunoprecipitation in vivo and in vitro; ChIP for H3K4me2; siRNA knockdown of ZNF217; expression analysis Experimental cell research Medium 30898548
2020 ZNF217 mediates matrix stiffness- and collagen density-induced increases in Akt activity and mammary epithelial cell proliferation; ZNF217 is regulated by miR-203, which is repressed by matrix stiffness. In a mouse mammographic density model, reduced miR-203 correlates with higher Zfp217 (murine homolog) and elevated Akt activity. ZNF217 manipulation in culture; miR-203 profiling; Akt activity assays; mouse mammographic density model; quantitative proteomics and mechanical measurements of breast stroma The Journal of clinical investigation Medium 32721948
2020 ZNF217 forced expression in PCOS theca cells reduces androgen (DHEA) production, CYP17A1 mRNA, and DENND1A.V2 mRNA, while increasing miR-130b-3p levels; conversely, ZNF217 knockdown in normal theca cells increases DENND1A.V2 and CYP17A1 mRNA. ZNF217 overexpression in PCOS theca cells; shRNA lentiviral knockdown in normal theca cells; RT-qPCR for CYP17A1, DENND1A.V2, miR-130b-3p; androgen production assays Journal of the Endocrine Society Medium 35668995
2022 ZNF217 upregulates NANOG expression by reducing N6-methyladenosine (m6A) levels via interaction with METTL3; co-immunoprecipitation and methylated-RNA binding protein IP and PAR-CLIP assays confirmed ZNF217 interferes with METTL3-dependent m6A methylation of NANOG mRNA, promoting EMT in breast cancer. Co-immunoprecipitation; methylated-RNA immunoprecipitation; PAR-CLIP; dual-luciferase assay for miR-135/ZNF217 interaction; ZNF217 knockdown; xenograft assays Oncogene Medium 35121826
2023 ZNF217 acts within a histone modifier complex containing LSD1, CoREST, and HDAC (confirmed by mass spectrometry), and knockout of ZNF217 in PMBCL cells changes chromatin accessibility at binding motifs for lymphoma-associated transcription factors, interfering with H3K4 methylation and H3K27 acetylation and altering expression of interferon-responsive genes. Targeted sequencing; ZNF217 knockout; mass spectrometry; gene expression profiling; ATAC-seq (chromatin accessibility); histone modification analysis Leukemia High 37648814
2023 ZNF217 activates Notch1 transcription (confirmed by dual-luciferase reporter assay) to sustain cancer stem cell self-renewal and colorectal CSC marker expression; Notch1 knockdown rescues ZNF217-overexpression-driven stem cell properties. Dual-luciferase reporter assay; ZNF217 overexpression; Notch1 knockdown; CSC marker and sphere formation assays; in vivo xenograft The Journal of nutritional biochemistry Medium 38134973
2023 Dimethyl fumarate (DMF) covalently modifies ZNF217 at cysteine residues (identified by cysteine-directed proteomics and confirmed with a DMF-chemical probe), inhibiting ZNF217 transcriptional activity on target genes and suppressing ZNF217-driven cancer phenotypes. Cysteine-directed activity-based proteomics; DMF-chemical probe confirmation; ZNF217 target gene expression analysis; gain/loss-of-function of ZNF217 combined with DMF treatment; xenograft assay Breast cancer research and treatment Medium 37477798
2024 ZNF217 transcriptionally activates GRHL3 expression in thyroid cancer cells; GRHL3 in turn activates SLC22A31 transcription, forming a ZNF217/GRHL3/SLC22A31 axis promoting thyroid cancer cell malignancy; rescue overexpression of GRHL3 or SLC22A31 abrogates the effects of ZNF217 knockdown. Lentiviral knockdown of ZNF217, GRHL3, SLC22A31; RT-qPCR; bioinformatics differential expression; functional rescue assays Molecular biotechnology Low 39354204
2025 ZNF217 is essential for B-ALL cell survival driven by MLL rearrangement or BCR-ABL; ZNF217 exerts oncogenic activity through both CoREST-dependent and CoREST-independent mechanisms; FOS is a direct downstream transcriptional target repressed by ZNF217 in a CoREST-independent manner (identified by integrated RNA-seq and CUT&RUN-seq). CRISPR-Cas9 screen; gain/loss-of-function assays; RNA-seq; CUT&RUN-seq; xenograft and PDX models Theranostics High 40093906
2025 ZNF217 and LSD1 co-occupy the EBV immediate-early gene BZLF1 promoter and oriLyt enhancer regions; knockout of ZNF217 or LSD1, or CoREST triggers EBV lytic reactivation, and LSD1 depletion increases H3K4 methylation (but not H3K9me) at BZLF1 and oriLyt, inducing their long-range looping. ZNF217 thus functions as a restriction factor for EBV lytic reactivation within the LSD1/ZNF217/CoREST complex. Genome-wide CRISPR-Cas9 screen; ZNF217/LSD1/CoREST knockout; ChIP for H3K4me; 3D chromatin (looping) analysis; EBV reactivation assays; LSD1 small molecule antagonist; ganciclovir cytotoxicity assays; murine xenograft Research square (preprint)preprint Medium 39877093
2025 ZNF217 promotes AML cell proliferation by directly activating MYB transcription; ZNF217 is part of the AML core transcriptional regulatory circuit (CRC) with ELF1, MEF2D, RUNX2, and FOXP1, sustaining super-enhancer activity through mutual auto-regulation loops. ZNF217 binding to MYB regulatory regions was confirmed by CUT&Tag. ChIP-seq analysis; CUT&Tag; shRNA knockdown; luciferase reporter assays; RNA-seq; in vitro and in vivo proliferation/viability assays International journal of biological sciences Medium 40083704

Source papers

Stage 0 corpus · 85 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Positional cloning of ZNF217 and NABC1: genes amplified at 20q13.2 and overexpressed in breast carcinoma. Proceedings of the National Academy of Sciences of the United States of America 274 9671742
2016 Hypoxia-inducible factors regulate pluripotency factor expression by ZNF217- and ALKBH5-mediated modulation of RNA methylation in breast cancer cells. Oncotarget 225 27590511
2001 The ZNF217 gene amplified in breast cancers promotes immortalization of human mammary epithelial cells. Cancer research 117 11245413
2020 Stiff stroma increases breast cancer risk by inducing the oncogene ZNF217. The Journal of clinical investigation 101 32721948
2006 Biochemical characterization of the zinc-finger protein 217 transcriptional repressor complex: identification of a ZNF217 consensus recognition sequence. Oncogene 93 17130829
2012 TGF-β-dependent active demethylation and expression of the p15ink4b tumor suppressor are impaired by the ZNF217/CoREST complex. Molecular cell 89 22560925
2013 Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 78 24336158
2006 Specific recognition of ZNF217 and other zinc finger proteins at a surface groove of C-terminal binding proteins. Molecular and cellular biology 75 16940172
2007 Identification of genes directly regulated by the oncogene ZNF217 using chromatin immunoprecipitation (ChIP)-chip assays. The Journal of biological chemistry 73 17259635
2009 The ZNF217 oncogene is a candidate organizer of repressive histone modifiers. Epigenetics 69 19242095
2016 Knockdown of lncRNA-ATB suppresses autocrine secretion of TGF-β2 by targeting ZNF217 via miR-200c in keloid fibroblasts. Scientific reports 67 27090737
2012 Identification of ZNF217, hnRNP-K, VEGF-A and IPO7 as targets for microRNAs that are downregulated in prostate carcinoma. International journal of cancer 65 22815235
2007 Amplification of zinc finger gene 217 (ZNF217) and cancer: when good fingers go bad. Biochimica et biophysica acta 65 17572303
2005 ZNF217 suppresses cell death associated with chemotherapy and telomere dysfunction. Human molecular genetics 61 16203743
2010 ZNF217, a candidate breast cancer oncogene amplified at 20q13, regulates expression of the ErbB3 receptor tyrosine kinase in breast cancer cells. Oncogene 56 20661224
2020 lncRNA SNHG1 Knockdown Alleviates Amyloid-β-Induced Neuronal Injury by Regulating ZNF217 via Sponging miR-361-3p in Alzheimer's Disease. Journal of Alzheimer's disease : JAD 55 32741808
2018 Suppression of lncRNA-ATB prevents amyloid-β-induced neurotoxicity in PC12 cells via regulating miR-200/ZNF217 axis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 52 30248538
2015 MiR-203 suppresses ZNF217 upregulation in colorectal cancer and its oncogenicity. PloS one 51 25621839
2015 The dark side of ZNF217, a key regulator of tumorigenesis with powerful biomarker value. Oncotarget 51 26431164
2004 The candidate oncogene ZNF217 is frequently amplified in colon cancer. The Journal of pathology 49 15476264
2011 Overexpression of ZNF217 in glioblastoma contributes to the maintenance of glioma stem cells regulated by hypoxia-inducible factors. Laboratory investigation; a journal of technical methods and pathology 47 21483406
2008 Genome analysis identifies the p15ink4b tumor suppressor as a direct target of the ZNF217/CoREST complex. Molecular and cellular biology 47 18625718
2010 ZNF217 confers resistance to the pro-apoptotic signals of paclitaxel and aberrant expression of Aurora-A in breast cancer cells. Molecular cancer 41 21059223
2007 Multiple roles of the candidate oncogene ZNF217 in ovarian epithelial neoplastic progression. International journal of cancer 40 17266044
2017 The critical role of the ZNF217 oncogene in promoting breast cancer metastasis to the bone. The Journal of pathology 39 28207159
2016 GATA3-driven expression of miR-503 inhibits prostate cancer progression by repressing ZNF217 expression. Cellular signalling 39 27267060
2021 CircLPAR1/miR-212-3p/ZNF217 feedback loop promotes amyloid β-induced neuronal injury in Alzheimer's Disease. Brain research 37 34403662
2014 A functional interplay between ZNF217 and estrogen receptor alpha exists in luminal breast cancers. Molecular oncology 34 24973012
2013 New insights into DNA recognition by zinc fingers revealed by structural analysis of the oncoprotein ZNF217. The Journal of biological chemistry 33 23436653
2020 OIP5-AS1/miR-137/ZNF217 Axis Promotes Malignant Behaviors in Epithelial Ovarian Cancer. Cancer management and research 32 32801903
2019 The coordination between ZNF217 and LSD1 contributes to hepatocellular carcinoma progress and is negatively regulated by miR-101. Experimental cell research 31 30898548
2011 The multi-zinc finger protein ZNF217 contacts DNA through a two-finger domain. The Journal of biological chemistry 31 21908891
2014 Global analysis of ZNF217 chromatin occupancy in the breast cancer cell genome reveals an association with ERalpha. BMC genomics 29 24962896
2014 Chromosome 20q13.2 ZNF217 locus amplification correlates with decreased E-cadherin expression in ovarian clear cell carcinoma with PI3K-Akt pathway alterations. Human pathology 28 25281027
2016 ZNF217/ZFP217 Meets Chromatin and RNA. Trends in biochemical sciences 27 27519282
2022 MicroRNA-135 inhibits initiation of epithelial-mesenchymal transition in breast cancer by targeting ZNF217 and promoting m6A modification of NANOG. Oncogene 26 35121826
2023 FTO-stabilized miR-139-5p targets ZNF217 to suppress prostate cancer cell malignancies by inactivating the PI3K/Akt/mTOR signal pathway. Archives of biochemistry and biophysics 24 37080415
2020 LncRNA MALAT1 promotes wound healing via regulating miR-141-3p/ZNF217 axis. Regenerative therapy 23 33426220
2008 The eukaryotic translation elongation factor eEF1A2 induces neoplastic properties and mediates tumorigenic effects of ZNF217 in precursor cells of human ovarian carcinomas. International journal of cancer 23 18661515
2022 The PCOS GWAS Candidate Gene ZNF217 Influences Theca Cell Expression of DENND1A.V2, CYP17A1, and Androgen Production. Journal of the Endocrine Society 22 35668995
2015 ZNF217 is overexpressed and enhances cell migration and invasion in colorectal carcinoma. Asian Pacific journal of cancer prevention : APJCP 22 25824781
2008 Silencing of ZNF217 gene influences the biological behavior of a human ovarian cancer cell line. International journal of oncology 22 18425333
2016 Elevated expression of ZNF217 promotes prostate cancer growth by restraining ferroportin-conducted iron egress. Oncotarget 21 27768596
2020 Long non-coding RNA CTBP1-AS2 enhances cervical cancer progression via up-regulation of ZNF217 through sponging miR-3163. Cancer cell international 19 32742190
2012 Gene amplification of ZNF217 located at chr20q13.2 is associated with lymph node metastasis in ovarian clear cell carcinoma. Anticancer research 18 22843878
2005 Detection of Her2/neu, c-MYC and ZNF217 gene amplification during breast cancer progression using fluorescence in situ hybridization. Oncology reports 17 15756435
2023 ZNF217-activated Notch signaling mediates sulforaphane-suppressed stem cell properties in colorectal cancer. The Journal of nutritional biochemistry 13 38134973
2021 ZNF217: the cerberus who fails to guard the gateway to lethal malignancy. American journal of cancer research 13 34354851
2020 Implication of ZNF217 in Accelerating Tumor Development and Therapeutically Targeting ZNF217-Induced PI3K-AKT Signaling for the Treatment of Metastatic Osteosarcoma. Molecular cancer therapeutics 13 32999043
2017 Zinc finger gene 217 (ZNF217) Promoted Ovarian Hyperstimulation Syndrome (OHSS) through Regulating E2 Synthesis and Inhibiting Thrombospondin-1 (TSP-1). Scientific reports 13 28607476
2023 Frequent ZNF217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma. Leukemia 11 37648814
2022 lncRNA PCAT1 might coordinate ZNF217 to promote CRC adhesion and invasion through regulating MTA2/MTA3/Snai1/E-cadherin signaling. Cellular and molecular biology (Noisy-le-Grand, France) 11 35809308
2019 A candidate pathogenic gene, zinc finger gene 217 (ZNF217), may contribute to polycystic ovary syndrome through prostaglandin E2. Acta obstetricia et gynecologica Scandinavica 10 31454071
2024 Hsa_circ_0049472 contributed to amyloid-beta peptide-induced neurotoxicity, apoptosis and inflammation via regulating PI3K-AKT signaling pathway by interacting with miR-22-3p/ZNF217 axis. Brain research bulletin 9 38852653
2022 The Intricate Interplay between the ZNF217 Oncogene and Epigenetic Processes Shapes Tumor Progression. Cancers 9 36551531
2010 CCND1 and ZNF217 gene amplification is equally frequent in BRCA1 and BRCA2 associated and non-BRCA breast cancer. Neoplasma 8 20429623
2010 Coexistence of copy number increases of ZNF217 and CYP24A1 in colorectal cancers in a Chinese population. Oncology letters 8 22966406
2021 CircCSNK1G1 Contributes to the Tumorigenesis of Gastric Cancer by Sponging miR-758 and Regulating ZNF217 Expression. Cancer management and research 7 34234548
2022 Long non-coding RNA HOXA11-AS contributes to the formation of keloid by relieving the inhibition of miR-182-5p on ZNF217. Burns : journal of the International Society for Burn Injuries 6 35987744
2021 Exploring the Significance of the Exon 4-Skipping Isoform of the ZNF217 Oncogene in Breast Cancer. Frontiers in oncology 6 34277402
2016 Regulation of expression of the p21CIP1 gene by the transcription factor ZNF217 and MDM2. Biochemistry and cell biology = Biochimie et biologie cellulaire 6 27792410
2025 CRISPR screening reveals ZNF217 as a vulnerability in high-risk B-cell acute lymphoblastic leukemia. Theranostics 5 40093906
2024 ZNF217: An Oncogenic Transcription Factor and Potential Therapeutic Target for Multiple Human Cancers. Cancer management and research 5 38259608
2022 Hsa_circ_0069094 positively regulates the expression of oncogenic ZNF217 by competitively targeting miR-758-3p to promote the development of breast cancer. Reproductive biology 5 36356557
2013 Learning the local Bayesian network structure around the ZNF217 oncogene in breast tumours. Computers in biology and medicine 5 23375235
2005 Coexistence of copy number changes of different genes (INK4A, erbB-1, erbB-2, CMYC, CCND1 and ZNF217) in urothelial tumors. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 5 15897688
2025 Core transcriptional regulatory circuitry molecule ZNF217 promotes AML cell proliferation by up-regulating MYB. International journal of biological sciences 4 40083704
2019 The ZNF217 Biomarker Predicts Low- and High-Risk Oncotype DX® Recurrence Score in ER-Positive Invasive Breast Cancers. Frontiers in pharmacology 4 31191299
2019 Retracted Article: Berberine alleviates amyloid beta-induced injury in Alzheimer's disease by miR-107/ZNF217. RSC advances 4 35528669
2025 The Histone Demethylase LSD1/ZNF217/CoREST Complex is a Major Restriction Factor of Epstein-Barr Virus Lytic Reactivation. Research square 3 39877093
2023 Dimethyl fumarate inhibits ZNF217 and can be beneficial in a subset of estrogen receptor positive breast cancers. Breast cancer research and treatment 3 37477798
2015 [Lentivirus-mediated shRNA targeting ZNF217 suppresses cell growth, migration, and invasion of glioma cells in vitro]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 3 26198954
2023 [Impacts of LncRNA NORAD on the Proliferation, Apoptosis, and Chemosensitivity of Non-small Cell Lung Cancer Cells by Regulating ZNF217 through MiR-199a-3p]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 2 37653011
2015 Effect of ZNF217 gene polymorphisms on colorectal cancer development in a Mexican population. Genetics and molecular research : GMR 2 25729968
2025 ZNF217 promotes ovarian cancer progression by impacting multiple pivotal steps in the metastatic process. NPJ precision oncology 1 41345234
2006 [Oncogene ZNF217 amplification on chromosome 20 q in ovarian serous cystadenocarcinoma and its clinical implications]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 1 16793610
2005 [Study on amplification of ZNF217 in primary gastric carcinoma]. Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery 1 16149004
2026 Chromatin Engagement and Transcriptional Activity of the ZNF217 Exon 4-Skipping Isoform Are Associated with Breast Cancer Aggressiveness and Bone Metastasis. Cancers 0 41749916
2026 UCMSC-derived exosomal circDLGAP4 enhances HFF-1 cell proliferation and migration by promoting ZNF217 promoter H3K27 acetylation. Molecular genetics and genomics : MGG 0 42191952
2025 Tumor suppressor FBXO11 drives ubiquitin proteasomal degradation of KIF2C to limit ovarian cancer progression and is transcriptionally repressed by ZNF217. Cellular signalling 0 40447129
2024 ZNF217 Gene Copy Number as a Marker of Response to Standard Therapy Drugs According to ERα Status in Breast Cancer. Breast cancer (Dove Medical Press) 0 38505863
2024 ZNF217 Mediates Transcriptional Activation of GRHL3 to Regulate SLC22A31 and Promote Malignant Progression in Thyroid Cancer. Molecular biotechnology 0 39354204
2013 [ZNF217 expression correlates with the biological behavior of human ovarian cancer cells]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 0 23879995
2009 [Expression of ZNF217 in human ovarian cystadenocarcinoma and its clinical significance]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 0 19403395
2006 [ZNF217 gene was detected in ovarian serous cystadenocarcinoma by fluorescence in situ hybridization]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 17160949

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