| 2005 |
HP1γ (CBX3) localizes to the transcribed regions of active genes in mammalian chromatin, and its presence there depends on elongation by RNA polymerase II, demonstrating a role for HP1γ in transcription elongation rather than exclusively in gene silencing. |
Chromatin immunoprecipitation (ChIP) across active genes; RNA polymerase II inhibition experiments |
Molecular cell |
High |
16061184
|
| 2007 |
Suv39H1 and HP1γ (CBX3), together with H3K9 trimethylation, mediate chromatin-based repression of integrated HIV-1 gene expression; RNAi knockdown of HP1γ reactivates HIV-1 transcription in latently infected cells including PBMCs from HIV-1-infected donors. |
RNAi knockdown, ChIP, transcription assays in multiple cellular models including primary PBMCs |
The EMBO journal |
High |
17245432
|
| 2000 |
HP1γ (CBX3) localizes to both euchromatin and heterochromatin compartments of interphase nuclei, and is present at pericentromeric chromatin and chromosome arms during mitosis; the N-terminal epitope is selectively masked in non-replicative heterochromatin, explaining prior contradictory localization reports. |
Immunocytochemistry with antibodies directed against distinct epitopes; GFP-fusion live imaging; immunofluorescence on 3T3 cells |
Cytogenetics and cell genetics |
High |
11124534
|
| 2011 |
HP1γ (CBX3) facilitates inclusion of alternative exons in CD44 pre-mRNA by decreasing RNA polymerase II elongation rate and stabilizing association of the pre-mRNA with chromatin; elevated H3K9me3 at alternative exons is required for HP1γ recruitment to these regions. |
ChIP, siRNA knockdown, splicing assays, RNA-chromatin association assays |
Nature structural & molecular biology |
High |
21358630
|
| 2009 |
HP1γ (CBX3) and cohesin are co-recruited to D4Z4 repeats in an H3K9me3-dependent and cell type-specific manner; SUV39H1-mediated H3K9me3 at D4Z4 is required for HP1γ/cohesin recruitment, and this is disrupted in FSHD. |
ChIP with D4Z4-specific primers; siRNA knockdown of SUV39H1; analysis of patient and normal cells |
PLoS genetics |
High |
19593370
|
| 2010 |
JMJD2A/KDM4A demethylase overexpression increases chromatin accessibility and antagonizes HP1γ-dependent S phase progression; overexpression of HP1γ antagonizes JMJD2A-dependent S phase acceleration, and this antagonism is conserved in C. elegans (HPL-2 vs JMJD-2). |
Genetic epistasis (double mutant/overexpression in mammalian cells and C. elegans), BrdU incorporation, replication timing assays |
Molecular cell |
High |
21145482
|
| 2012 |
CBX3 (HP1γ) binds to gene bodies genome-wide in a manner correlating with gene activity; CBX3 depletion leads to accumulation of unspliced nascent transcripts and defective recruitment of splicing factors (SNRNP70) to target genes, indicating a role in efficient cotranscriptional RNA processing. |
Genome-wide ChIP-seq, RNAi knockdown, RNA-seq, splicing factor ChIP |
Genome research |
High |
22684280
|
| 2011 |
HP1γ (CBX3/Cbx3) links H3K9me2 at pericentric heterochromatin to meiotic synapsis; H3K9me2 at PCH depends on Suv39h1/h2-mediated H3K9me3 recognized by Cbx3/HP1γ, and Cbx3-deficient spermatocytes show defective centromere clustering and synapsis similar to G9a-deficient animals. |
Cbx3 knockout mouse generation, comparative analysis with Suv39h1/h2 and G9a knockout spermatocytes, genetic epistasis |
Development (Cambridge, England) |
High |
21896631
|
| 2010 |
HP1γ (CBX3) is required for male germ cell survival and spermatogenesis; hypomorphic Cbx3 mice show severe hypogonadism with germ cell loss and increased L1 retrotransposon expression (ORF1p), indicating a role for HP1γ in transposon silencing in germ cells. |
Gene-targeted hypomorphic mouse (Cbx3hypo), immunostaining, L1 ORF1p detection |
Epigenetics & chromatin |
High |
20423503
|
| 2008 |
During HIV-1 LTR activation, HP1β is replaced by HP1γ on the promoter; HP1γ localizes both to the promoter and inside the coding region together with processive RNA polymerase II, while HP1β acts as a repressor with non-processive RNA polymerase II before stimulation. |
ChIP time-course during HIV-1 LTR activation, RNAi knockdown of HP1 isoforms |
EMBO reports |
High |
18239689
|
| 2012 |
The CBX3 chromodomain binds not only H3K9me3 but also dimethylated histone H1K26 and trimethylated G9aK185 with comparable affinities; crystal structures of the human CBX3 chromodomain in complex with H1K26me2 and G9aK185me3 peptides reveal a conserved binding mechanism. |
Crystal structure determination, binding affinity assays (ITC/fluorescence), structural analysis |
PloS one |
High |
22514736
|
| 2014 |
Shigella OspF phosphothreonine lyase interacts with HP1γ and inactivates ERK/MSK1 to reduce HP1γ phosphorylation at serine 83 (S83); MSK1 is identified as a novel HP1γ kinase that phosphorylates HP1γ at S83 in an MSK1-HP1γ complex, promoting HP1γ accumulation at target genes. |
Co-IP (MSK1-HP1γ complex), in vitro kinase assay, phospho-specific antibodies, ChIP, transcriptome analysis, guinea pig in vivo model |
The EMBO journal |
High |
25216677
|
| 2013 |
HP1γ interacts with BRCA1 and regulates BRCA1-mediated transcription; following DNA damage, HP1γ disassembles from the promoter while BRCA1 is recruited, and after repair, HP1γ reassembles via its BRCA1 interaction, recruiting SUV39H1 to restore H3K9 methylation and transcriptional repression. |
Co-IP (HP1γ-BRCA1), ChIP time-lapse after DNA damage, HP1γ mutant analysis, siRNA of histone methyltransferases |
Nucleic acids research |
High |
23074186
|
| 2011 |
Histone variant H3.3 and HP1γ cooperate to activate HSP70 transcription upon heat shock; H3.3 promotes stable HP1γ recruitment to HSP70 promoters, and HP1γ selectively recognizes specific modification states of H3.3 in the nucleosome; knockdown of either H3.3 or HP1γ attenuates HSP70 promoter activity. |
ChIP, siRNA knockdown, reporter assays, nucleosome binding assays |
Nucleic acids research |
Medium |
21742762
|
| 2011 |
Recruitment of NIPBL (cohesin loading factor) to DNA double-strand break sites requires HP1γ; NIPBL's C-terminal HEAT repeat region containing an HP1-interacting motif mediates this recruitment, and HP1γ depletion by RNAi compromises NIPBL accumulation at damaged sites. |
RNAi knockdown, micro-irradiation DSB assays, I-PpoI endonuclease DSB assays, NIPBL domain deletion analysis |
Biochemical and biophysical research communications |
Medium |
21784059
|
| 2015 |
HP1γ binding to H3K9me3-containing nucleosomes is strongly enhanced by nucleosome compaction (induced by Mg2+ or linker histone H1), whereas HP1α can bind uncompacted nucleosomes; the hinge region connecting the chromodomain and chromoshadow domain accounts for this distinct recognition property. |
In vitro reconstituted tetra-nucleosome binding assays, Mg2+ and linker histone H1 compaction, domain analysis |
Nucleic acids research |
High |
26319017
|
| 2013 |
Aurora A kinase phosphorylates HP1γ at serine 83 (S83) during G2/M phase; non-phosphorylatable S83A-HP1γ cannot rescue mitotic aberrations caused by HP1γ knockdown, while phosphomimetic S83D-HP1γ increases EdU incorporation, establishing an Aurora A-HP1γ pathway required for proper somatic cell division. |
Immunofluorescence co-localization, site-directed mutagenesis (S83A/S83D), siRNA knockdown, proliferation assays, genome-wide expression profiling |
Epigenetics & chromatin |
High |
23829974
|
| 2017 |
CBX3/HP1γ binds to gene promoters upon neural differentiation and recruits the Mediator subunit Med26; RNAi knockdown of Cbx3 or Med26 inhibits neural differentiation while upregulating mesodermal lineage genes, establishing a Cbx3-Med26 axis for lineage fidelity. |
ChIP-seq, RNAi knockdown, RNA-seq, neural differentiation assays of murine ESCs |
Genes & development |
High |
28270516
|
| 2017 |
HP1γ (CBX3) directly represses expression of NCOR2 and ZBTB7A through its H3K9me3-binding chromodomain; binding activity to methylated H3K9 is required for HP1γ-dependent proliferation, colony formation, and migration of lung adenocarcinoma cells, and NCOR2/ZBTB7A knockdown restores these defects in HP1γ-depleted cells. |
Chromodomain mutant analysis, ChIP, siRNA epistasis, proliferation/migration assays, in vivo K-RasG12D mouse model |
Cancer research |
High |
29764865
|
| 2018 |
CBX3 inhibits VSMC proliferation and migration by transcriptionally repressing Notch3 through a transcriptional repression mechanism; Notch3 reactivation reverses the effects of CBX3 overexpression on VSMC proliferation and migration, and CBX3 overexpression reduces neointima formation after carotid wire injury in vivo. |
Luciferase reporter assays, overexpression/knockdown, carotid wire injury mouse model, gene expression analysis |
Cardiovascular research |
High |
29206900
|
| 2018 |
CBX3 negatively regulates FBP1 expression to promote aerobic glycolysis in pancreatic cancer cells; FBP1 silencing attenuates the decrease in glycolytic capacity caused by CBX3 knockdown. |
CBX3 siRNA knockdown, glycolysis assays, FBP1 expression analysis, rescue experiments |
Biochemical and biophysical research communications |
Medium |
29678579
|
| 2019 |
HP1γ (CBX3) is citrullinated at R38 and R39 within its chromodomain by PAD4 in mouse ESCs; citrullination at these residues diminishes H3K9me3 binding in vitro and reduces HP1γ residence time on chromatin in vivo; H3K9me3 peptides enhance PAD4-mediated citrullination of HP1γ. |
In vitro citrullination/PAD4 assay, mutagenesis (R38/R39), H3K9me3 binding assay, live-cell single-particle tracking |
Epigenetics & chromatin |
High |
30194940
|
| 2019 |
HP1γ is citrullinated in mouse ESCs by PAD4; citrullination is dynamically regulated during differentiation and diminishes when cells differentiate. |
Mass spectrometry-based detection of citrullination, in vitro PAD4 assay |
Epigenetics & chromatin |
High |
30940194
|
| 2018 |
NGF-PKA signaling during neuronal differentiation leads to phosphorylation of HP1γ at S83 via PKA, decreased association with heterochromatin, and subsequent proteasomal degradation of HP1γ; forced HP1γ overexpression antagonizes neuronal differentiation. |
Gain-of-function/loss-of-function in PC12 cells, phospho-specific antibody, co-immunoprecipitation, genome-wide expression profiling |
Scientific reports |
Medium |
30305677
|
| 2020 |
HP1γ (CBX3) regulates H3K36me3 levels at genic regions in ESCs through interaction with NSD1 (an H3K36 methyltransferase) via its chromoshadow and hinge domains, independently of its chromodomain H3K9me3-reading activity; HP1γ deletion reduces H3K36me3 and impairs ESC self-renewal and cardiac mesoderm differentiation. |
HP1γ deletion ESCs, ChIP-seq (H3K36me3/H3K9me3), domain mutant analysis, Co-IP of HP1γ with NSD1 |
Nucleic acids research |
High |
33237287
|
| 2021 |
HP1γ binds hexameric RNA motifs and SINE family transposable elements in introns via its RNA-binding activity; this tethers unspliced pre-mRNA to chromatin and limits usage of intronic cryptic splice sites, linking HP1γ RNA-binding to co-transcriptional splicing regulation. |
RNA immunoprecipitation (RIP), CLIP-seq, RNA-seq splicing analysis, HP1γ mutant analysis |
EMBO reports |
High |
34312949
|
| 2020 |
HPV E6 protein drives nuclear export of HP1γ via interaction between the HP1γ NES sequence and exportin-1 (Crm-1); cytoplasmic HP1γ can no longer suppress UBE2L3, leading to UBE2L3-mediated E6-dependent p53 polyubiquitination and degradation. NES mutation in HP1γ retains it in the nucleus, reduces UBE2L3 expression, and suppresses cervical cancer cell growth. |
Immunostaining, NES mutagenesis, Co-IP (E6-HP1γ, exportin-1), leptomycin B treatment, tumor xenograft |
Cell death and differentiation |
High |
32203172
|
| 2017 |
HP1γ (CBX3) is present not only in the nucleus but also in the cytoplasm where it interacts with actin; HP1γ co-immunoprecipitates with actin in both nuclear and cytosolic fractions of myoblasts, co-localizes with the perinuclear actin cap, and HP1γ-actin associates with the promoter and transcribed regions of the GAPDH housekeeping gene by re-ChIP; HP1γ knockdown prevents myoblast differentiation. |
Subcellular fractionation, Co-IP in nuclear and cytosolic fractions, immunoelectron microscopy, confocal microscopy, re-ChIP |
Biochimica et biophysica acta. Molecular cell research |
Medium |
29208528
|
| 2023 |
HDAC1 deacetylates HP1γ at lysine 5 in bortezomib-resistant myeloma cells, preventing ubiquitin-mediated degradation; deacetylated HP1γ interacts with MDC1 to promote DNA repair and induces nuclear condensation, increasing chromatin accessibility at target genes (CD40, FOS, JUN) to confer drug resistance. |
SILAC-based acetyl-proteomics, Co-IP (HP1γ-MDC1), HDAC1 inhibitor, HP1γ acetylation mutants, ChIP-seq, in vitro and in vivo drug resistance assays |
Nature communications |
High |
36894562
|
| 2024 |
CBX3 binds the histone acetyltransferase EP300 and increases EP300 substrate specificity toward lactyl-CoA, promoting histone lactylation and an immunosuppressive transcriptional program in glioblastoma stem cells; CBX3 does not have direct lactyltransferase activity but acts as a co-factor for EP300-mediated lactylation. |
Co-IP (CBX3-EP300), lactylation assays, siRNA knockdown, transcriptomic analysis, phagocytosis assays |
The Journal of clinical investigation |
Medium |
39545414
|
| 2024 |
CBX3 binds RPA2 and inhibits RFWD3-facilitated replication restart at stalled replication forks; CK2 phosphorylates CBX3 at serine-95, which promotes CDH1-mediated CBX3 degradation and RPA2 dynamics, permitting fork restart; elevated CBX3 sensitizes prostate cancer cells to PARP inhibitors. |
Co-IP (CBX3-RPA2), in vitro kinase assay (CK2), stalled fork assays, RFWD3 epistasis, PARP inhibitor sensitivity assays |
Science advances |
High |
38781342
|
| 2021 |
CBX3 forms a repressive complex with TRIM28 and TRIM24 and RBBP4 that represses ARHGAP24 expression, leading to increased active Rac1 levels and LUAD progression. |
Co-IP of CBX3-TRIM28-TRIM24-RBBP4 complex, ChIP at ARHGAP24, Rac1 activity assay, functional proliferation/migration assays |
Oncogene |
Medium |
34785774
|
| 2023 |
PLK1 phosphorylates CBX3 to enhance CBX3 interaction with RB1, releasing E2F1 and desensitizing prostate cancer cells to CDK4/6 inhibitors; BRD4 transcriptionally upregulates CBX3 expression in CRPC cells. |
Co-IP (CBX3-RB1), ChIP (BRD4 at CBX3 promoter), phosphorylation assays, CDK4/6 inhibitor sensitivity experiments |
Advanced science |
Medium |
37949681
|
| 2024 |
CBX3 directly binds to STAT1 and CD274 (PD-L1) promoters to repress their transcription; IFNγ reduces CBX3 binding to these promoters; CBX3 deletion results in chronic colon inflammation with upregulated STAT1 and PD-L1 expression; CBX3 antagonizes IFNγ signaling in colon epithelium. |
ChIP (CBX3 at STAT1 and CD274 promoters), CBX3 knockout mouse, IFNγ stimulation, CRC chemosensitivity assays |
EMBO molecular medicine |
High |
38684864
|
| 2025 |
SETDB1 mediates H3K9me3 at the SIRT4 promoter and recruits CBX3 to repress SIRT4 expression in kidney proximal tubular cells during ischemia-reperfusion injury; CBX3 and SETDB1 interact as shown by Co-IP and ChIP-reChIP, and SETDB1 knockdown upregulates SIRT4, promoting autophagy and protecting against injury. |
ChIP, sequential ChIP (re-ChIP), Co-IP (SETDB1-CBX3), gene expression analysis, in vivo rat I/R model |
FASEB journal |
Medium |
40197868
|
| 2023 |
CBX3 directly suppresses CUL3 transcription by binding to its promoter, thereby reducing CUL3-mediated NRF2 degradation and upregulating GPX4 expression; this CBX3/CUL3/NRF2/GPX2 axis inhibits ferroptosis and mediates multidrug resistance in colorectal cancer. |
RNA-seq, ChIP (CBX3 at CUL3 promoter), NRF2 pathway inhibition, ferroptosis assays, PDX models |
Oncogene |
Medium |
40089640
|
| 2025 |
HP1γ chromoshadow domain (HP1γCSD) recognizes the HP1 box of KAP1 and forms a dimer-of-dimers in an antiparallel arrangement; crystal structure, NMR, and mass photometry reveal this is distinct from HP1αCSD which oligomerizes in a parallel arrangement; KAP1 and HP1γ cooperate specifically (not other HP1s) to repress lncRNA AI662270 in ESCs. |
Crystallography, NMR, mass photometry, in vivo rescue experiments in KAP1/HP1-knockout ESCs |
Cell reports |
High |
41575850
|
| 2025 |
TRIM66 interacts with HP1γ through a PxVxL motif; TRIM66 enables HP1γ co-phase separation (LLPS) in vitro and in vivo, and TRIM66-HP1γ liquid granules co-localize with H3K9me3 chromatin sites, remodeling facultative heterochromatin in association with DNA damage response. |
Co-IP (TRIM66-HP1γ PxVxL interaction), in vitro LLPS assay, in vivo granule formation, H3K9me3 co-localization |
Biophysics reports |
Medium |
40070663
|
| 2023 |
Mouse HP1γ regulates TRF1 expression transcriptionally; HP1γ-deficient MEFs show downregulation of TRF1 and other telomere factor transcripts, increased telomeric DNA-RNA hybrids (R-loops), elevated TERRA from specific chromosomes, and increased telomere replication stress (γH2AX), particularly in females. |
HP1γ KO MEFs, gene expression analysis, telomere FISH, DNA-RNA immunoprecipitation (DRIP), immunofluorescence |
Life sciences |
Medium |
37598977
|
| 2024 |
CBX3 cooperates with EP300 to upregulate GPX4 expression in circulating tumor cells, protecting them from ferroptosis during blood-borne metastasis; CBX3 depletion triggers ferroptosis and reduces tumor cell survival. |
Single-cell RNA-seq, Co-IP (CBX3-EP300), GPX4 ChIP, CBX3 KD/overexpression, ferroptosis assays, in vivo metastasis model |
Journal of hematology & oncology |
Medium |
41540451
|
| 2015 |
CBX3 (HP1γ) mass spectrometry interactome analysis identifies 99 binding proteins enriched in spliceosome, DNA repair, and replication pathways; HP1γ is functionally active in DNA damage response via these protein interactions. |
Affinity purification of FLAG-HP1γ from G1/S and prometaphase cell lysates followed by mass spectrometry |
Cancer research and treatment |
Low |
25761473
|