Affinage

CBX7

Chromobox protein homolog 7 · UniProt O95931

Length
251 aa
Mass
28.3 kDa
Annotated
2026-04-28
100 papers in source corpus 34 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CBX7 is a Polycomb Repressive Complex 1 (PRC1) subunit that functions as a multivalent chromatin reader integrating histone, DNA, and RNA recognition to enforce transcriptional silencing at developmental and tumor-suppressor loci, while also exhibiting cell-type-specific roles as a transcriptional activator and cytoplasmic signaling scaffold. Its N-terminal chromodomain recognizes H3K27me3 (preferentially on Ser31-phosphorylated H3.3 nucleosomes) through an aromatic cage, and an adjacent AT-hook-like motif cooperatively binds DNA; the chromodomain also engages noncoding RNA (ANRIL) and mRNA 3′ UTRs, with nucleic-acid and histone binding allosterically coupled (PMID:20541999, PMID:27723458, PMID:29073373, PMID:41582043). CBX7 recruits Ring1B to chromatin in embryonic stem cells to maintain pluripotency and repress early-lineage genes, while at other loci it assembles repressive complexes containing HDAC2, DNMTs, SUV39H2, or the H3K9 methyltransferases SETDB1/EHMT1/EHMT2 to silence targets including INK4a/ARF, CCNE1, and FGFR3 (PMID:23273917, PMID:22214847, PMID:19602592, PMID:21060834, PMID:30759399). CBX7 protein stability is regulated by ubiquitin-dependent proteasomal degradation mediated by E3 ligases RNF26 and RNF2, and its activity is modulated by MAPK-mediated Thr-118 phosphorylation; in lymphoid cells, CBX7 unexpectedly translocates to the cytosol to form a methylation-dependent signaling complex with c-Raf, MEK1/2, and CK2-α that sustains ERK signaling, while in cardiomyocytes it interacts with TARDBP to regulate RBM38-dependent cell-cycle exit (PMID:35342353, PMID:39456039, PMID:24194518, PMID:41686891, PMID:37158107).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2003 High

    Establishing CBX7 as a Polycomb group protein that extends replicative lifespan by repressing Ink4a/Arf resolved the question of which PcG protein directly silences this senescence-controlling locus independently of Bmi1.

    Evidence Co-IP with Ring1, immunofluorescence to Polycomb bodies, shRNA knockdown with growth/lifespan assays in human fibroblasts

    PMID:14647293

    Open questions at the time
    • Genome-wide targets beyond Ink4a/Arf not identified
    • Mechanism of chromatin recruitment not resolved
    • How CBX7 and Bmi1 complexes partition was unclear
  2. 2007 High

    Demonstrating that Cbx7 overexpression initiates T-cell lymphoma and cooperates with c-Myc in B-cell lymphoma established CBX7 as an oncogene acting epistatically upstream of Arf-p53, resolving whether its Ink4a/Arf repression was tumorigenic in vivo.

    Evidence Lymphoid-targeted Cbx7 transgenic mice, genetic epistasis with Ink4a/Arf deletion and p53 pathway

    PMID:17374722

    Open questions at the time
    • Whether CBX7 has tumor-suppressive roles in other tissues was unknown
    • Mechanism of tissue-specific oncogenicity unclear
  3. 2009 Medium

    Identifying CBX7 association with DNA methyltransferases showed that PRC1 can initiate stable DNA hypermethylation at target promoters, linking Polycomb silencing to permanent epigenetic memory.

    Evidence Co-IP of CBX7-DNMT complexes, ChIP and methylation analysis in embryonal carcinoma cells

    PMID:19602592

    Open questions at the time
    • DNMT interaction characterized by single-lab pulldown only
    • Which DNMT isoform is principally recruited was not resolved
    • Genome-wide extent of CBX7-dependent DNA methylation unknown
  4. 2010 High

    Structural and biochemical dissection of the CBX7 chromodomain revealed dual recognition of H3K27me3 and ANRIL ncRNA, answering how CBX7 achieves locus-specific targeting at INK4a/ARF through combinatorial chromatin and RNA readout.

    Evidence NMR structure of chromodomain, RNA-binding assays, chromodomain mutagenesis, ChIP and senescence assays

    PMID:20541999

    Open questions at the time
    • Which other ncRNAs contribute to CBX7 targeting was unknown
    • Relative contributions of RNA vs. histone binding to genome-wide occupancy not quantified
  5. 2010 Medium

    Discovery that CBX7 recruits SUV39H2 to deposit H3K9me3 at the p16 promoter revealed a PRC1-H3K9 methylation crosstalk mechanism, expanding the epigenetic toolkit downstream of CBX7 beyond canonical PRC1 activities.

    Evidence BiFC, Co-IP, ChIP, and siRNA knockdown of Suv39h2 in human cells

    PMID:21060834

    Open questions at the time
    • Single-lab observation without independent replication
    • Whether SUV39H2 interaction is direct or mediated by other PRC1 subunits unclear
  6. 2012 High

    Three contemporaneous studies established Cbx7 as the dominant PRC1 chromodomain subunit in ESCs—required for Ring1B chromatin recruitment, self-renewal maintenance, and repression of lineage-commitment genes and alternative Cbx paralogs—resolving how PRC1 composition is specified in pluripotent cells.

    Evidence ChIP-seq, Co-IP, siRNA/overexpression, miRNA screens, differentiation assays in mouse ESCs; Cbx7-KO mouse with liver/lung carcinomas and HDAC2 Co-IP

    PMID:22214847 PMID:22226354 PMID:23273917

    Open questions at the time
    • How Cbx7-to-Cbx2/4 switching is executed during differentiation was not mechanistically resolved
    • Whether Cbx7-PRC1 and RYBP-PRC1 co-occupy any loci was untested
  7. 2013 High

    Identification of MAPK-mediated phosphorylation at Thr-118 showed that extracellular signals dynamically modulate CBX7's PRC1 interactions and repressive activity, answering how CBX7 function is tuned by signaling inputs.

    Evidence Mass spectrometry, phospho-specific antibody, MEK inhibitor treatment, Co-IP after EGF stimulation, RAS-induced senescence assay

    PMID:24194518

    Open questions at the time
    • Whether other kinases phosphorylate CBX7 was unknown
    • Effect of Thr-118 phosphorylation on chromatin occupancy genome-wide not tested
  8. 2014 High

    Development of peptidomimetic inhibitors with crystal structures of the CBX7 chromodomain–ligand complexes provided the first chemical tools to probe CBX7 function and revealed structural features unique to CBX7 among human CBX paralogs, enabling selective pharmacological perturbation.

    Evidence X-ray crystallography, NMR, fluorescence polarization, isothermal titration calorimetry

    PMID:24625057 PMID:25660273

    Open questions at the time
    • Cell permeability and in vivo efficacy of early compounds not established
    • Whether inhibitors affect CBX7-RNA interactions was untested
  9. 2016 High

    Live-cell single-molecule tracking combined with biochemical analysis identified an AT-hook-like motif that cooperates with the chromodomain for DNA binding, establishing that CBX7 chromatin targeting requires bivalent histone-DNA co-recognition rather than H3K27me3 alone.

    Evidence Single-molecule tracking, CRISPR-mediated H3K27me3 ablation, DNA-binding assays with CBX7 mutants

    PMID:27723458

    Open questions at the time
    • Sequence specificity of DNA binding not fully resolved
    • How ATL motif integrates with RNA binding was unclear
  10. 2017 High

    Genome-wide dCLIP revealed that CBX7 binds predominantly to mRNA 3′ UTRs via defined consensus motifs, uncovering an unexpected post-transcriptional dimension of CBX7 function beyond canonical chromatin silencing.

    Evidence dCLIP-seq with motif mutagenesis validation in vitro, ASO intervention in mouse and human cells

    PMID:29073373

    Open questions at the time
    • Functional consequence of mRNA binding on translation/stability not determined for most targets
    • Whether mRNA binding occurs in the nucleus, cytoplasm, or both was not resolved
  11. 2019 High

    Mass spectrometry-based interactomics revealed that CBX7 non-canonically engages H3K9 methyltransferases SETDB1, EHMT1, and EHMT2 via their trimethylated lysine motifs, establishing a PRC1-H3K9me crosstalk axis critical for HSPC self-renewal in AML.

    Evidence MS interactome, Co-IP, shRNA depletion phenocopying in AML cells, xenotransplantation

    PMID:30759399

    Open questions at the time
    • Whether CBX7 chromodomain directly reads methylated lysines on SETDB1/EHMTs or requires an adaptor was unclear
    • Contribution of this axis to normal hematopoiesis vs. leukemogenesis not separated
  12. 2019 Medium

    A positive allosteric modulator (UNC4976) demonstrated that CBX7's histone-binding and nucleic-acid-binding activities are allosterically coupled, establishing a pharmacological principle for redistributing PRC1 away from H3K27me3-marked loci.

    Evidence Fluorescence polarization, three orthogonal cellular assays, ChIP

    PMID:31422906

    Open questions at the time
    • Single-lab observation
    • In vivo effects of allosteric modulation not tested
    • Structural basis of allosteric coupling not resolved
  13. 2020 Medium

    Identification of two CBX7 isoforms (p36/nuclear, p22/cytoplasmic) with opposing effects on proliferation revealed that alternative isoform usage partitions CBX7 between chromatin repression and cytoplasmic functions.

    Evidence Subcellular fractionation, immunofluorescence, serum-starvation induction, proliferation assays

    PMID:32205869 PMID:32415167

    Open questions at the time
    • Molecular determinants of isoform switching unknown
    • Cytoplasmic binding partners of p22 not identified
    • Whether p22 retains RNA-binding capacity untested
  14. 2022 Medium

    Discovery that RNF26 ubiquitinates CBX7 for proteasomal degradation identified the first E3 ligase controlling CBX7 protein turnover, explaining how CBX7 levels are post-translationally tuned in renal cell carcinoma.

    Evidence Co-IP, ubiquitination assay, cycloheximide chase, xenograft model

    PMID:35342353

    Open questions at the time
    • Single-lab observation
    • Ubiquitination site(s) on CBX7 not mapped
    • Whether RNF26-mediated degradation operates in normal tissues unknown
  15. 2023 High

    Identification of the CBX7–TARDBP–RBM38 axis in cardiomyocytes established a non-canonical mechanism by which CBX7 enforces postnatal cell-cycle exit, answering why Cbx7 loss permits cardiomyocyte proliferation and heart regeneration after injury.

    Evidence Co-IP, mass spectrometry, conditional cardiac KO mice (Tnnt2-Cre and Myh6-MCM), neonatal and adult injury models

    PMID:37158107

    Open questions at the time
    • Whether the CBX7-TARDBP interaction is chromodomain-dependent or Pc-box-dependent not resolved
    • How this axis interfaces with canonical PRC1 silencing in cardiomyocytes unknown
  16. 2024 Medium

    Discovery that CBX7 undergoes liquid-liquid phase separation with ATP7A, trapping the copper transporter intracellularly and triggering cuproptosis in aged hearts, revealed a previously unrecognized biophysical mechanism linking CBX7 to copper homeostasis and cardiac aging.

    Evidence LLPS assay, protein interaction assay, scRNA-seq, high-throughput compound screening, mouse and minipig MI models

    PMID:41117088

    Open questions at the time
    • Single-lab finding; LLPS mechanism not reconstituted with purified components
    • Whether other PRC1 subunits participate in or modulate LLPS unknown
    • Generalizability beyond cardiac tissue untested
  17. 2024 Medium

    Pharmacological CBX7 inhibition abolished interactions with EHMT1/2 and SETDB1 and showed additive anti-leukemic effects with H3K9 methyltransferase inhibitors, validating the CBX7-H3K9me axis as a druggable node in AML.

    Evidence Co-IP, H3K9me ChIP, pharmacological inhibition, proliferation/differentiation assays in leukemic cells

    PMID:39613290

    Open questions at the time
    • In vivo pharmacokinetics and efficacy not reported
    • Whether inhibitor selectivity among CBX paralogs is sufficient for therapeutic use unknown
  18. 2026 High

    Biochemical and ChIP-seq studies showed CBX7 preferentially reads Ser31-phosphorylated H3.3K27me3, recruiting KAP1 and H3K9 methyltransferase to establish heterochromatin and silence retrotransposons; this axis is also required for H3K9me2/3 accumulation on the inactive X chromosome, unifying CBX7's heterochromatin roles across developmental contexts.

    Evidence Nucleosome binding assays, Co-IP (CBX7-KAP1), ChIP-seq (H3K9me3), retrotransposon reactivation, X-inactivation assays with interaction-blocking mutations

    PMID:41582043

    Open questions at the time
    • Which kinase deposits Ser31 phosphorylation to prime CBX7 recruitment is unknown
    • Structural basis of Ser31-phospho recognition by CBX7 not determined
  19. 2026 High

    Discovery that CBX7 functions as both a transcriptional activator and a cytoplasmic ERK-signaling scaffold in lymphoid (but not epithelial) cells fundamentally expanded the functional repertoire of PRC1 subunits, revealing cell-type-specific non-canonical roles.

    Evidence Co-IP (CBX7–c-Raf, MEK1/2, CK2-α), ChIP at cytokine promoters, RNA-seq, genetic KO and pharmacological inhibition in lymphoid cells, allergic asthma mouse models

    PMID:41686891

    Open questions at the time
    • What determines the switch from repressor to activator in lymphoid cells is unknown
    • Whether the cytoplasmic signaling role requires the p22 isoform specifically is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the structural basis for allosteric coupling between histone, DNA, and RNA binding; how cell-type-specific isoform usage and post-translational modifications partition CBX7 between canonical PRC1 silencing, transcriptional activation, cytoplasmic signaling, and phase-separation functions; and whether pharmacological targeting of CBX7 can achieve paralog selectivity sufficient for therapeutic use in cancer or cardiac regeneration.
  • No full-length CBX7 structure exists
  • Isoform-specific interactomes not systematically compared
  • In vivo efficacy of CBX7 inhibitors not demonstrated in disease models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 7 GO:0140110 transcription regulator activity 6 GO:0003723 RNA binding 3 GO:0003677 DNA binding 2 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3 GO:0005829 cytosol 2
Pathway
R-HSA-4839726 Chromatin organization 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-168256 Immune System 1
Partners
EHMT1EHMT2HDAC2KAP1RING1RNF2SETDB1TARDBP
Complex memberships
CBX7-HDAC2 repressive complexCBX7-SETDB1/EHMT1/EHMT2 complexCBX7-c-Raf/MEK1/2/CK2-α cytoplasmic signaling complexPRC1 (Cbx7-Ring1B canonical PRC1)

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 CBX7 chromodomain binds both trimethylated histone H3K27me3 and the noncoding RNA ANRIL; both interactions are required for CBX7-mediated repression of the INK4b/ARF/INK4a locus. Structure-guided NMR analysis revealed the molecular interplay between RNA and H3K27me3 binding within the conserved chromodomain, and disruption of either interaction impairs senescence control. Co-IP, NMR structure, RNA-binding assays, chromodomain mutagenesis, ChIP, senescence assays Molecular cell High 20541999
2003 CBX7 is a Polycomb group protein that interacts with Ring1, localizes to nuclear Polycomb bodies, and extends cellular lifespan by repressing the Ink4a/Arf locus through the p16(Ink4a)/Rb and Arf/p53 pathways; it does not co-localize or interact functionally with Bmi1. Genetic screen, Co-IP, shRNA knockdown, immunofluorescence localization, functional lifespan and growth assays Nature cell biology High 14647293
2012 Cbx7 is the primary PRC1 Polycomb ortholog in mouse embryonic stem cells (ESCs); it directly represses Cbx2, Cbx4, and Cbx8, and its expression is regulated by the miR-125 and miR-181 families. Cbx7 loss induces ESC differentiation while its ectopic expression inhibits differentiation and enhances self-renewal. Gain- and loss-of-function (KD/OE), ChIP, functional miRNA screen, differentiation assays, X-chromosome inactivation assays Cell stem cell High 22226354
2012 In mouse ESCs, Cbx7 (but not RYBP) is necessary for recruitment of Ring1B to chromatin; Cbx7-containing PRC1 complexes and RYBP-containing PRC1 complexes are mutually exclusive and regulate distinct gene sets, with Cbx7-occupied genes controlling early-lineage commitment. ChIP-seq, Co-IP, siRNA knockdown, Ring1B chromatin fractionation, gene expression profiling Cell reports High 23273917
2007 Cbx7 initiates T cell lymphomagenesis in mice and cooperates with c-Myc to produce B cell lymphomas; it represses the Ink4a/Arf locus and acts epistatically upstream of the Arf-p53 pathway during tumorigenesis. Transgenic mouse model (lymphoid-targeted Cbx7 expression), genetic epistasis, tumor analysis, Ink4a/Arf expression assays Proceedings of the National Academy of Sciences of the United States of America High 17374722
2012 CBX7 acts as a tumor suppressor by binding to the CCNE1 (cyclin E) promoter in a complex with HDAC2 to negatively regulate cyclin E expression; Cbx7-knockout mice develop liver and lung adenomas and carcinomas, with upregulated cyclin E. Cbx7-KO mouse generation, ChIP, Co-IP with HDAC2, gene expression analysis in KO MEFs and tumors, in vivo/in vitro assays The Journal of clinical investigation High 22214847
2015 The CBX7 chromodomain binds H3K27me3 through an aromatic cage; small molecules (MS37452) that occupy the methyl-lysine binding pocket competitively inhibit this interaction and derepress p16/CDKN2A in prostate cancer cells by displacing CBX7 from the INK4A/ARF locus. Crystal structures of CBX7ChD-ligand complexes, fluorescence polarization binding assays, ChIP in prostate cancer cells Chemistry & biology High 25660273
2016 Live-cell single-molecule tracking revealed that Cbx7 is targeted to chromatin by co-recognition of H3K27me3 and DNA; biochemical analysis identified an AT-hook-like (ATL) motif that, together with the chromodomain, constitutes a functional DNA-binding unit. Disrupting PRC1 complex formation facilitates Cbx7 chromatin targeting. Live-cell single-molecule tracking (SMT), genetic engineering of Cbx7 mutants, biochemical DNA-binding assays, CRISPR-based H3K27me3 disruption eLife High 27723458
2014 Peptidomimetic inhibitors of CBX7 targeting the H3K27me3-binding chromodomain were developed; NMR and X-ray crystal structures of ligand-chromodomain complexes revealed a structural motif unique to CBX7 among human CBX proteins, enabling ~200 nM potency with 10-fold selectivity over CBX8. Fluorescence polarization, isothermal titration calorimetry, 2D NMR, X-ray crystallography Journal of medicinal chemistry High 24625057
2009 CBX7 associates with DNA methyltransferase (DNMT) enzymes and can initiate stable epigenetic silencing of genes frequently hypermethylated in cancer. In embryonal carcinoma cells, CBX7 promotes DNMT assembly at target gene promoters and initiates DNA hypermethylation. Co-IP (CBX7-DNMT complex), ChIP, shRNA knockdown, gene expression and methylation assays in EC cells Cancer research Medium 19602592
2010 CBX7 directly initiates H3K9me3 formation at the p16 promoter by forming a complex with the methyltransferase SUV39H2; this interaction was demonstrated by bimolecular fluorescence complementation and co-IP, and requires an intact chromodomain and Pc-box. siRNA knockdown of Suv39h2 blocks CBX7-mediated p16 repression. Co-IP, bimolecular fluorescence complementation (BiFC), ChIP, siRNA knockdown, CBX7 chromodomain/Pc-box mutants PloS one Medium 21060834
2013 MAPK signaling phosphorylates Cbx7 at Thr-118 (near the conserved Polycomb box); this phosphorylation, detected by a site-specific antibody and mass spectrometry, moderately enhances p16 repression and is induced upon EGF stimulation, which also triggers robust interaction of Cbx7 with other PRC1 members. Mass spectrometry, site-specific antibody, MEK inhibitor treatment, Co-IP after EGF stimulation, RAS-induced senescence assay The Journal of biological chemistry High 24194518
2017 dCLIP (denaturing CLIP) showed that CBX7 predominantly binds 3' UTRs of messenger RNAs with a median footprint of ~171-183 nucleotides. Four families of consensus RNA-binding motifs were identified; their mutation abolishes CBX7 binding in vitro. Antisense oligonucleotide (ASO) intervention paradoxically increases CBX7 binding and enhances gene expression. dCLIP-seq (UV crosslink immunoprecipitation with denaturation), bioinformatics motif analysis, in vitro binding with mutant motifs, ASO treatment Cell systems High 29073373
2019 CBX7 interacts non-canonically with H3K9 methyltransferases SETDB1, EHMT1, and EHMT2 (which contain trimethylated lysine motifs similar to H3K27me3); mass spectrometry identified these interactions, and depletion of SETDB1 in AML cells phenocopies CBX7 repression, establishing a non-canonical crosstalk pathway that controls HSPC self-renewal. Mass spectrometry interactome, Co-IP, genetic depletion (shRNA), AML cell proliferation and differentiation assays, xenotransplantation Cell reports High 30759399
2019 A positive allosteric modulator (PAM) peptidomimetic UNC4976 simultaneously antagonizes H3K27me3-specific recruitment of CBX7 to target genes while increasing non-specific binding to DNA and RNA, thereby reequilibrating PRC1 away from H3K27me3-marked regions. This reveals that CBX7 nucleic acid binding and histone binding are allosterically coupled. Quantitative cellular assay, fluorescence polarization, three orthogonal cellular assays, ChIP Cell chemical biology Medium 31422906
2016 Structure-guided discovery identified Class A CBX7 chromodomain antagonists that inhibit methyl-lysine binding and Class B compounds (MS351) that inhibit H3K27me3 binding when CBX7 is bound to RNA. Crystal structure of CBX7ChD/MS351 reveals ligand recognition by aromatic cage residues that engage methyl-lysine. MS351 induces transcriptional derepression of p16(INK4a) in ESCs and prostate cancer cells. Crystal structure of CBX7ChD/MS351 complex, fluorescence polarization, ChIP, gene expression assays ACS medicinal chemistry letters High 27326334
2014 CBX7 inhibits breast tumorigenicity by increasing DKK-1 transcription through cooperation with p300 acetyltransferase, enhancing histone acetylation at the DKK-1 promoter, thereby suppressing Wnt/β-catenin/TCF signaling. Pharmacological DKK-1 inhibition reverses CBX7-mediated Wnt suppression. ChIP (histone acetylation at DKK-1 promoter), Co-IP (CBX7-p300), luciferase reporter assay, shRNA KD, pharmacological inhibitor rescue, in vivo tumor initiation assay FASEB journal Medium 25351982
2020 CBX7 binds the E-box and prevents TWIST-1 from binding its transcriptional targets in secondary epithelial ovarian cancer cells; deletion of CBX7 is sufficient to reactivate TWIST-1-induced transcription and restore mesenchymal transformation and tumorigenicity. CBX7 deletion (CRISPR/genetic), E-box binding assay, in vitro and in vivo tumorigenicity assays, EMT marker analysis Oncogene Medium 32205869
2016 CBX7 represses YAP/TAZ-dependent transcription in glioma cells, leading to downregulation of CTGF and reduced phospho-JNK; CBX7 overexpression inhibits cell migration, and migration inhibition is reversed by exogenous CTGF or constitutively active JNK. Cbx7 promoter is hypermethylated in GBM. GSEA of CBX7-regulated genes, Western blot (YAP/TAZ, CTGF, pJNK), exogenous CTGF rescue, constitutively active JNK rescue, bisulfite sequencing Scientific reports Medium 27291091
2021 CBX7 suppresses AKR1B10 transcription in a PRC1-dependent manner in bladder cancer cells; loss of CBX7 leads to AKR1B10 upregulation that activates ERK signaling. This was established by RNA-seq and ChIP assays identifying AKR1B10 as a direct downstream target. RNA-seq, ChIP, siRNA knockdown, small molecule inhibitor (oleanolic acid), in vivo tumor model Cell death & disease Medium 34035231
2023 CBX7 interacts with TARDBP (TDP-43) and positively regulates its downstream target RBM38 in a TARDBP-dependent manner; this axis mediates CBX7-directed cell cycle exit of postnatal cardiomyocytes. Genetic inactivation of Cbx7 in cardiomyocytes increased proliferation, impeded cardiac maturation, and promoted heart regeneration after injury. Co-immunoprecipitation, mass spectrometry, conditional cardiac KO mice (Tnnt2-Cre and Myh6-MCM), adenoviral OE, neonatal apical resection and adult MI models, proliferation marker immunostaining Circulation High 37158107
2020 Two CBX7 isoforms (p36 and p22) have distinct subcellular localizations and opposing roles: p36CBX7 localizes to the nucleus and is expressed in proliferating cells, whereas p22CBX7 localizes to the cytoplasm, is induced by serum starvation, and inhibits cell proliferation. Subcellular fractionation, immunofluorescence, serum starvation experiments, proliferation assays Scientific reports Medium 32415167
2018 CBX7 regulates axon growth and regeneration in neurons; knockdown of CBX7 in embryonic cortical neurons or adult DRG neurons enhances axon growth ability. GATA4 and SOX11 are functional downstream transcriptional targets of CBX7 in controlling axon regeneration; knockdown of GATA4 or SOX11 inhibits CBX7-knockdown-induced axon regeneration. CBX7 shRNA KD in primary neurons, DRG axon regeneration assays, genetic epistasis (GATA4/SOX11 KD rescue) Cell death and differentiation Medium 29459770
2022 RNF26 acts as an E3 ubiquitin ligase that promotes ubiquitination and proteasomal degradation of CBX7 protein (without affecting CBX7 mRNA), thereby activating the TNF/ETS1 signaling pathway to promote ccRCC growth. Co-IP, ubiquitination assay, cycloheximide chase (protein stability), shRNA/OE, xenograft mouse model International journal of biological sciences Medium 35342353
2022 EZH2 represses CBX7 expression by increasing H3K27me3 at the CBX7 locus in bladder cancer cells; CBX7 in turn directly downregulates FGFR3 expression (confirmed by ChIP) and sensitizes bladder cancer cells to cisplatin by inactivating the PI3K/AKT signaling pathway. ChIP-qPCR (H3K27me3 at CBX7 locus; CBX7 binding at FGFR3 promoter), Western blot, RT-qPCR, CCK-8, xenograft model British journal of cancer Medium 36396821
2024 RNF2 promotes ubiquitination and proteasomal degradation of CBX7 protein (without affecting CBX7 mRNA); knockdown of RNF2 upregulates CBX7 and reduces chondrosarcoma cell proliferation, migration, and angiogenesis, effects reversed by CBX7 knockdown. Co-IP, ubiquitination assay, cycloheximide chase, siRNA/OE, xenograft mouse model Cancer & metabolism Medium 39456039
2019 HIF-1α transcriptionally activates CBX7 expression during hypoxia/ischemia, and this HIF-1α-CBX7 cascade modulates neural progenitor cell (NPC) proliferation; CBX7-knockout mice generated by CRISPR/Cas9 show significantly reduced NPC numbers. ChIP (HIF-1α at CBX7 promoter), CRISPR/Cas9 KO mice, NPC proliferation assays, hypoxia model Neuropathology and applied neurobiology Medium 31630421
2024 CBX7 promotes meningioma progression control by transcriptionally repressing USP44, a deubiquitinase for c-MYC; loss of CBX7 leads to USP44-mediated c-MYC stabilization, increased LDHA transactivation, and enhanced glycolysis. Restoration of CBX7 triggers a metabolic shift from glycolysis to oxidative phosphorylation. iTRAQ proteomics, ChIP, luciferase reporter assay, siRNA/OE, subcutaneous and orthotopic xenograft models Journal of molecular cell biology Medium 37791390
2026 CBX7 preferentially binds Ser31-phosphorylated H3.3K27me3 nucleosomes and recruits KAP1, which engages histone lysine 9 methyltransferase to establish H3K9me3-associated heterochromatin. Disrupting the H3.3-CBX7 interaction significantly impairs H3K9me3 and activates retrotransposons; the same axis is required for H3K9me2/3 accumulation at the inactive X during X-chromosome inactivation. Biochemical nucleosome binding assays, Co-IP (CBX7-KAP1), ChIP-seq (H3K9me3), retrotransposon activation assays, X-inactivation analysis with H3.3-CBX7 interaction-blocking mutations Science bulletin High 41582043
2026 CBX7 forms a methylation-dependent transcriptional activation complex at cytokine gene promoters (unexpectedly inducing transcription) and also translocates to the cytosol where it forms a methylation-dependent signaling complex with c-Raf, MEK1/2, and CK2-α to generate sustained ERK1/2 signaling in lymphoid cells; both activities are absent in epithelial cells. Co-IP (CBX7-c-Raf, MEK1/2, CK2-α), ChIP (CBX7 at cytokine promoters), RNA-seq, genetic KO and pharmacological inhibition in mouse and human lymphoid cells, allergic asthma mouse models Science advances High 41686891
2024 In aged hearts, CBX7 forms liquid-liquid phase separation (LLPS) with ATP7A, trapping ATP7A intracellularly and reducing copper efflux, thereby triggering cuproptosis; a small-molecule inhibitor (δ-Amyrenone) that disrupts CBX7-ATP7A LLPS restores ATP7A trafficking and improves cardiac function. LLPS assay, protein interaction assay (CBX7-ATP7A), single-cell RNA-seq, high-throughput screening, in vivo mouse and minipig MI models Advanced science Medium 41117088
2022 Exosomal circ_0006790 facilitates nuclear translocation of CBX7; nuclear CBX7 then recruits DNA methyltransferases to the S100A11 promoter to increase S100A11 DNA methylation and suppress its transcription, thereby inhibiting PDAC immune escape. Exosome treatment, nuclear fractionation, ChIP (DNMT recruitment to S100A11 promoter), siRNA KD of CBX7, rescue with S100A11 OE American journal of cancer research Medium 35693076
2025 DNMT1 methylates the CBX7 promoter to suppress CBX7 expression in PDAC; silencing DNMT1 upregulates CBX7, which reduces ERK phosphorylation and suppresses tumor progression. ChIP and dual-luciferase assays confirmed direct DNMT1 binding and methylation of the CBX7 promoter. ChIP-qPCR (DNMT1 at CBX7 promoter), dual-luciferase reporter assay, siRNA knockdown, Western blot, CCK-8, wound healing, transwell assays FASEB journal Medium 40387566
2024 CBX7 inhibition by small molecules abolishes CBX7 interaction with H3K9 methyltransferases EHMT1/2 and SETDB1, reduces H3K9 methylation, reactivates target gene expression, and has additive effects with EHMT1/2 or SETDB1 inhibitors on reducing leukemic cell growth and inducing differentiation. Co-IP (CBX7-EHMT1/2-SETDB1), pharmacological CBX7 inhibition, H3K9 methylation ChIP, gene expression assays, cell proliferation and differentiation assays Experimental hematology Medium 39613290

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Molecular cell 1125 20541999
2003 Polycomb CBX7 has a unifying role in cellular lifespan. Nature cell biology 264 14647293
2012 MicroRNA regulation of Cbx7 mediates a switch of Polycomb orthologs during ESC differentiation. Cell stem cell 170 22226354
2012 RYBP and Cbx7 define specific biological functions of polycomb complexes in mouse embryonic stem cells. Cell reports 168 23273917
2007 Role of the chromobox protein CBX7 in lymphomagenesis. Proceedings of the National Academy of Sciences of the United States of America 141 17374722
2012 CBX7 is a tumor suppressor in mice and humans. The Journal of clinical investigation 125 22214847
2005 CBX7 controls the growth of normal and tumor-derived prostate cells by repressing the Ink4a/Arf locus. Oncogene 122 15897876
2015 Small-molecule modulators of methyl-lysine binding for the CBX7 chromodomain. Chemistry & biology 97 25660273
2016 Live-cell single-molecule tracking reveals co-recognition of H3K27me3 and DNA targets polycomb Cbx7-PRC1 to chromatin. eLife 94 27723458
2018 CBX7 regulates stem cell-like properties of gastric cancer cells via p16 and AKT-NF-κB-miR-21 pathways. Journal of hematology & oncology 93 29422082
2014 Chromodomain antagonists that target the polycomb-group methyllysine reader protein chromobox homolog 7 (CBX7). Journal of medicinal chemistry 79 24625057
2010 Identification of a New Pathway for Tumor Progression: MicroRNA-181b Up-Regulation and CBX7 Down-Regulation by HMGA1 Protein. Genes & cancer 69 21779448
2014 CBX7 inhibits breast tumorigenicity through DKK-1-mediated suppression of the Wnt/β-catenin pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 62 25351982
2009 Polycomb CBX7 promotes initiation of heritable repression of genes frequently silenced with cancer-specific DNA hypermethylation. Cancer research 62 19602592
2010 Oncogenic role of the chromobox protein CBX7 in gastric cancer. Journal of experimental & clinical cancer research : CR 55 20723236
2016 Structure-Guided Discovery of Selective Antagonists for the Chromodomain of Polycomb Repressive Protein CBX7. ACS medicinal chemistry letters 54 27326334
2015 Polycomb protein family member CBX7 plays a critical role in cancer progression. American journal of cancer research 53 26175930
2019 Discovery and Characterization of a Cellular Potent Positive Allosteric Modulator of the Polycomb Repressive Complex 1 Chromodomain, CBX7. Cell chemical biology 48 31422906
2021 CBX7 suppresses urinary bladder cancer progression via modulating AKR1B10-ERK signaling. Cell death & disease 44 34035231
2018 Robustness of In Vitro Selection Assays of DNA-Encoded Peptidomimetic Ligands to CBX7 and CBX8. SLAS discovery : advancing life sciences R & D 42 29309209
2017 CBX7 suppresses cell proliferation, migration, and invasion through the inhibition of PTEN/Akt signaling in pancreatic cancer. Oncotarget 42 28030829
2010 Polycomb CBX7 directly controls trimethylation of histone H3 at lysine 9 at the p16 locus. PloS one 42 21060834
2018 miRNA-19 promotes non-small-cell lung cancer cell proliferation via inhibiting CBX7 expression. OncoTargets and therapy 36 30584339
2016 Ago-RIP-Seq identifies Polycomb repressive complex I member CBX7 as a major target of miR-375 in prostate cancer progression. Oncotarget 36 27449098
2021 Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer. Molecular oncology 35 33400401
2020 CBX7 binds the E-box to inhibit TWIST-1 function and inhibit tumorigenicity and metastatic potential. Oncogene 33 32205869
2017 CBX7 negatively regulates migration and invasion in glioma via Wnt/β-catenin pathway inactivation. Oncotarget 33 28388562
2019 CBX7 Induces Self-Renewal of Human Normal and Malignant Hematopoietic Stem and Progenitor Cells by Canonical and Non-canonical Interactions. Cell reports 32 30759399
2016 Cbx7 is epigenetically silenced in glioblastoma and inhibits cell migration by targeting YAP/TAZ-dependent transcription. Scientific reports 32 27291091
2015 Up-regulation of miR-9 target CBX7 to regulate invasion ability of bladder transitional cell carcinoma. Medical science monitor : international medical journal of experimental and clinical research 32 25596753
2014 CBX7 modulates the expression of genes critical for cancer progression. PloS one 29 24865347
2012 Tumor suppressor activity of CBX7 in lung carcinogenesis. Cell cycle (Georgetown, Tex.) 29 22544325
2020 The Crosstalk between lncRNA-SNHG7/miRNA-181/cbx7 Modulates Malignant Character in Lung Adenocarcinoma. The American journal of pathology 28 32201260
2019 CBX7 Inhibits Cell Growth and Motility and Induces Apoptosis in Cervical Cancer Cells. Molecular therapy oncolytics 28 31709304
2013 Synthetic trimethyllysine receptors that bind histone 3, trimethyllysine 27 (H3K27me3) and disrupt its interaction with the epigenetic reader protein CBX7. Bioorganic & medicinal chemistry 28 24100156
2015 Restoration of CBX7 expression increases the susceptibility of human lung carcinoma cells to irinotecan treatment. Naunyn-Schmiedeberg's archives of pharmacology 24 26216446
2022 Circ_0006790 carried by bone marrow mesenchymal stem cell-derived exosomes regulates S100A11 DNA methylation through binding to CBX7 in pancreatic ductal adenocarcinoma. American journal of cancer research 23 35693076
2017 miR-155 is positively regulated by CBX7 in mouse embryonic fibroblasts and colon carcinomas, and targets the KRAS oncogene. BMC cancer 23 28259135
2017 The malignancy of miR-18a in human glioblastoma via directly targeting CBX7. American journal of cancer research 22 28123848
2017 Denaturing CLIP, dCLIP, Pipeline Identifies Discrete RNA Footprints on Chromatin-Associated Proteins and Reveals that CBX7 Targets 3' UTRs to Regulate mRNA Expression. Cell systems 22 29073373
2022 The RNF26/CBX7 axis modulates the TNF pathway to promote cell proliferation and regulate sensitivity to TKIs in ccRCC. International journal of biological sciences 21 35342353
2015 CBX7 and miR-9 are part of an autoregulatory loop controlling p16(INK) (4a). Aging cell 20 26416703
2020 CBX7 suppression prevents ischemia-reperfusion injury-induced endoplasmic reticulum stress through the Nrf-2/HO-1 pathway. American journal of physiology. Renal physiology 19 32390514
2018 [ARTICLE WITHDRAWN] MicroRNA-18a Targets IRF2 and CBX7 to Promote Cell Proliferation in Hepatocellular Carcinoma. Oncology research 19 29386090
2023 Polycomb Group Protein CBX7 Represses Cardiomyocyte Proliferation Through Modulation of the TARDBP/RBM38 Axis. Circulation 18 37158107
2021 PDE4B Induces Epithelial-to-Mesenchymal Transition in Bladder Cancer Cells and Is Transcriptionally Suppressed by CBX7. Frontiers in cell and developmental biology 18 34977026
2021 CBX7 is Dualistic in Cancer Progression Based on its Function and Molecular Interactions. Frontiers in genetics 17 34659360
2019 Single Nucleotide Polymorphisms of CBX4 and CBX7 Decrease the Risk of Hepatocellular Carcinoma. BioMed research international 17 31211140
2018 Potential role of CBX7 in regulating pluripotency of adult human pluripotent-like olfactory stem cells in stroke model. Cell death & disease 17 29717132
2015 Critical evaluation of Cbx7 downregulation in primary colon carcinomas and its clinical significance in Chinese patients. BMC cancer 17 25881303
2018 Polycomb protein family member CBX7 regulates intrinsic axon growth and regeneration. Cell death and differentiation 16 29459770
2020 lncRNA NEAT1 Facilitates Cell Proliferation, Invasion and Migration by Regulating CBX7 and RTCB in Breast Cancer. OncoTargets and therapy 15 32273717
2020 Resveratrol inhibits oral squamous cell carcinoma cells proliferation while promoting apoptosis through inhibition of CBX7 protein. Environmental toxicology 15 32621571
2014 Tracing dynamics and clonal heterogeneity of Cbx7-induced leukemic stem cells by cellular barcoding. Stem cell reports 15 25434821
2016 Structure-Activity Relationships of Cbx7 Inhibitors, Including Selectivity Studies against Other Cbx Proteins. ACS omega 14 30023485
2023 Adipose-derived exosomal miR-421 targets CBX7 and promotes metastatic potential in ovarian cancer cells. Journal of ovarian research 13 38037081
2020 Regulation of circGOLPH3 and its binding protein CBX7 on the proliferation and apoptosis of prostate cancer cells. Bioscience reports 13 33245100
2022 Downregulation of CBX7 induced by EZH2 upregulates FGFR3 expression to reduce sensitivity to cisplatin in bladder cancer. British journal of cancer 12 36396821
2016 CBX7 deficiency plays a positive role in dentin and alveolar bone development. Journal of molecular histology 12 27271093
2022 Liver-specific deletion of miR-181ab1 reduces liver tumour progression via upregulation of CBX7. Cellular and molecular life sciences : CMLS 11 35867177
2022 Knockdown of CBX7 inhibits ferroptosis in rats with cerebral ischemia and improves cognitive dysfunction by activating the Nrf2/HO-1 pathway. Journal of biosciences 11 36222130
2013 Mitogen-activated protein kinase signaling mediates phosphorylation of polycomb ortholog Cbx7. The Journal of biological chemistry 11 24194518
2024 IGF-1-mediated FOXC1 overexpression induces stem-like properties through upregulating CBX7 and IGF-1R in esophageal squamous cell carcinoma. Cell death discovery 10 38413558
2022 CBX7 regulates metastasis of basal-like breast cancer through Twist1/EphA2 pathway. Translational oncology 10 35843065
2020 MicroRNA-18a suppresses ovarian carcinoma progression by targeting CBX7 and regulating ERK/MAPK signaling pathway and epithelial-to-mesenchymal transition. European review for medical and pharmacological sciences 10 32495862
2019 Mechanisms of ischaemic neural progenitor proliferation: a regulatory role of the HIF-1α-CBX7 pathway. Neuropathology and applied neurobiology 10 31630421
2008 [MiR-9 regulates the expression of CBX7 in human glioma]. Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 10 18686603
2023 LncRNA RNA ROR Aggravates Hypoxia/Reoxygenation-Induced Cardiomyocyte Ferroptosis by Targeting miR-769-5p/CBX7 Axis. Biochemical genetics 9 38157079
2020 Mammalian CBX7 isoforms p36 and p22 exhibit differential responses to serum, varying functions for proliferation, and distinct subcellular localization. Scientific reports 9 32415167
2018 Effect of CBX7 deficiency on the socket healing after tooth extractions. Journal of bone and mineral metabolism 8 30238429
2024 CBX7 promotes choroidal neovascularization by activating the HIF-1α/VEGF pathway in choroidal vascular endothelial cells. Experimental eye research 7 39179168
2021 Expression and correlation analysis of Skp2 and CBX7 in cervical cancer. Journal of clinical pathology 7 34281957
2019 Rational Adaptation of L3MBTL1 Inhibitors to Create Small-Molecule Cbx7 Antagonists. ChemMedChem 7 31254321
2018 The molecular selectivity of UNC3866 inhibitor for Polycomb CBX7 protein from molecular dynamics simulation. Computational biology and chemistry 6 29723807
2014 CBX7 Expression in Oncocytic Thyroid Neoplastic Lesions (Hürthle Cell Adenomas and Carcinomas). European thyroid journal 6 25759796
2024 CBX7 reprograms metabolic flux to protect against meningioma progression by modulating the USP44/c-MYC/LDHA axis. Journal of molecular cell biology 5 37791390
2024 RNF2 promotes chondrosarcoma progression by regulating ubiquitination and degradation of CBX7. Cancer & metabolism 5 39456039
2023 Subcellular expression pattern and clinical significance of CBX2 and CBX7 in breast cancer subtypes. Medical molecular morphology 5 37553450
2022 CBX7 represses the POU2F2 to inhibit the PD-L1 expression and regulate the immune response in bladder cancer. Biochemical and biophysical research communications 5 35526483
2017 Aza-amino acid scanning of chromobox homolog 7 (CBX7) ligands. Journal of peptide science : an official publication of the European Peptide Society 5 28220557
2017 Producing GST-Cbx7 Fusion Proteins from Escherichia coli. Bio-protocol 5 28966944
2024 CBX7 silencing promoted liver regeneration by interacting with BMI1 and activating the Nrf2/ARE signaling pathway. Scientific reports 3 38744845
2024 Targeting the Ferroptosis and Endoplasmic Reticulum Stress Signaling Pathways by CBX7 in Myocardial Ischemia/reperfusion Injury. Cell biochemistry and biophysics 3 38809351
2023 CBX7 Rejuvenates Late Passage Dental Pulp Stem Cells by Maintaining Stemness and Pro-angiogenic Ability. Tissue engineering and regenerative medicine 3 36920677
2023 Cbx7 promotes the generation of induced pluripotent stem cells. Regenerative therapy 3 37753387
2023 Decoding the interaction between miR-19a and CBX7 focusing on the implications for tumor suppression in cancer therapy. Medical oncology (Northwood, London, England) 3 38112798
2024 A novel nanoplatform-based circCSNK1G3 affects CBX7 protein and promotes glioma cell growth. International journal of biological macromolecules 2 39033888
2022 The expression of miR-181b, CYLD, CBX-7, BCL2, and p53 in osteosarcoma patients and correlation with clinicopathological factors. Chemical biology & drug design 2 36098711
2020 lncRNA NEAT1 Facilitates Cell Proliferation, Invasion and Migration by Regulating CBX7 and RTCB in Breast Cancer [Retraction]. OncoTargets and therapy 2 32848416
2025 Genome-wide association study reveals CBX7 as a novel susceptibility gene associated with primary spontaneous pneumothorax in the Chinese Han population. The European respiratory journal 1 40473309
2025 Chromobox protein homolog 7 (CBX7) deficiency inhibits osteoblast ferroptosis by activating the Nrf2 function in type 2 diabetic osteoporosis. The international journal of biochemistry & cell biology 1 40998236
2025 Engineered Multifunctional Hydrogel Delivering Novel CBX7 Inhibitor Modulates Cuproptosis Via Liquid-Liquid Phase Separation to Restore Cardiac Function in Aged Myocardial Infarction. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 41117088
2025 CBX7 regulates chemotherapy-induced senescence-like growth arrest in multiple myeloma via the ERK/STAT3/PIM1 axis. Journal of translational medicine 1 41250171
2024 CBX7 inhibitors affect H3K9 methyltransferase-regulated gene repression in leukemic cells. Experimental hematology 1 39613290
2023 CBX7 is involved in the progression of cervical cancer through the ITGβ3/TGFβ1/AKT pathway. Oncology letters 1 38028179
2026 Histone H3.3 phosphorylation facilitates H3K9me3-heterochromatin formation during retrotransposon silencing and X-chromosome inactivation via H3.3K27me3-CBX7-KAP1 axis. Science bulletin 0 41582043
2026 CBX7 functions as a methylation-dependent inducer of gene transcription and regulator of cytosolic signaling in lymphoid cells. Science advances 0 41686891
2025 DNMT1-Induced Downregulation of CBX7 Inhibits ERK Phosphorylation and Promotes Pancreatic Ductal Adenocarcinoma Progression. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 40387566
2024 Pharmacological targeting of CBX7 alters the epigenetic landscape and induces differentiation of leukemic cells. Blood neoplasia 0 40552137
2023 Adipose-derived exosomal miR-421 targets CBX7 and promotes metastatic potential in ovarian cancer cells. bioRxiv : the preprint server for biology 0 37986971