Affinage

JARID2

Protein Jumonji · UniProt Q92833

Length
1246 aa
Mass
138.7 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

JARID2 is a chromatin-associated regulatory subunit of Polycomb Repressive Complex 2 (PRC2) that calibrates the genomic targeting and enzymatic output of H3K27me3 deposition at developmental genes (PMID:20075857, PMID:20064375). It is a stable PRC2 component required for the bulk of PRC2 occupancy across PcG target genes and is sufficient to recruit PRC2 to a heterologous promoter, with its loss collapsing PRC2 binding and H3K27me3 (PMID:20075857). JARID2 directs PRC2 to chromatin through multiple recruitment modes: an N-terminal ubiquitin interaction motif that binds H2AK119ub1 to couple PRC1 and PRC2 activities (PMID:27892467), and a discrete RNA-binding region that engages long noncoding RNAs—including Meg3 and Xist—to bridge PRC2 to target loci and to the inactive X chromosome (PMID:24374312, PMID:24462204). Beyond recruitment, JARID2 is itself a PRC2 substrate: EZH2-mediated methylation of JARID2 is read by EED and allosterically activates PRC2, and structural work shows methylated JARID2 mimics a methylated H3 tail while contacting both EED and H2AK119-ubiquitin to stimulate methyltransferase activity, enabling de novo H3K27me3 deposition even on substrates that disfavor core PRC2 (PMID:25620564, PMID:29348366, PMID:33479123, PMID:31479253). Through these activities JARID2 governs cell-fate decisions in ES cells, cardiac and endothelial development, epidermal and skeletal-muscle differentiation, and hematopoiesis, frequently by PRC2-dependent repression of specific targets such as Notch1, Isl1, cyclin D1, SFRP1, and PTEN (PMID:21402699, PMID:21811233, PMID:30119689, PMID:31578284, PMID:27259236, PMID:29891551). In a context-dependent manner JARID2 also acts outside canonical PRC2: it partners with the H3K9 methyltransferases G9a/GLP and SETDB1 to repress cyclin D1 and Notch1 (PMID:19010785, PMID:22110129), associates with the NuRD complex to silence tumor-suppressor genes (PMID:37658635), and in lineage-committed keratinocytes exists as an N-terminally cleaved form (ΔN-JARID2) lacking the PRC2-interacting domain that promotes differentiation-gene activation independently of PRC2 (PMID:30573669).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2008 High

    Before its PRC2 role was known, JARID2 (Jmj) was shown to act as a transcriptional repressor by templating H3K9 methylation, establishing it as a chromatin-modifying scaffold rather than an independent enzyme.

    Evidence Co-IP, in vitro HMT assay, ChIP, and G9a/GLP double-knockdown epistasis at the cyclin D1 promoter

    PMID:19010785

    Open questions at the time
    • Did not establish JARID2's relationship to PRC2 or H3K27 methylation
    • Mechanism of JARID2 recruitment to the cyclin D1 promoter not defined
  2. 2009 High

    JARID2 was defined as a bona fide PRC2 subunit that simultaneously promotes PRC2 recruitment yet inhibits its in vitro activity, framing it as a 'molecular rheostat' for developmental gene regulation.

    Evidence Co-IP, genome-wide ChIP-seq of Jarid2/Ezh2/Suz12, in vitro HMT assay ± Jarid2, Xenopus knockdown

    PMID:20064375

    Open questions at the time
    • The apparent in vitro inhibition versus in vivo recruitment paradox unresolved
    • No structural basis for the activity modulation
  3. 2010 High

    Multiple studies established that JARID2 is genome-wide required for PRC2 occupancy and for co-recruitment of PRC1 and paused RNA Pol II, defining it as the principal targeting determinant of PRC2 in ES cells.

    Evidence Reciprocal Co-IP, genome-wide ChIP-seq, heterologous promoter recruitment assay, Jarid2-null ES cells with chromatin profiling

    PMID:20075857 PMID:20473294

    Open questions at the time
    • Molecular mechanism by which JARID2 selects target loci not yet defined
    • Did not explain how recruitment is coupled to enzymatic activation
  4. 2011 High

    JARID2 was shown to be a conserved PRC2 cofactor whose loss specifically affects H3K27me3, and to synergize with MTF2 and esPRC2p48 to stimulate PRC2 activity and reprogramming, beginning to reconcile its dual recruitment/activity roles.

    Evidence Mass spectrometry of ES-cell PRC2, reconstituted in vitro HMT assays, Drosophila genetic mutants and ChIP-seq, iPSC reprogramming assay

    PMID:21732481 PMID:22354997

    Open questions at the time
    • How cofactor combinations physically reorganize PRC2 not yet shown
    • Did not identify the chromatin signal driving JARID2-dependent targeting
  5. 2011 High

    Tissue-specific deletions revealed that JARID2 controls discrete differentiation programs by direct repression of lineage genes, linking its molecular activity to organ development.

    Evidence Conditional Cre-loxP knockouts in endothelium and epidermis, ChIP at Notch1 and differentiation loci, H3K27me3 ChIP, proliferation assays

    PMID:21402699 PMID:21811233 PMID:22110129

    Open questions at the time
    • Whether cardiac repression operates through PRC2 or H3K9 routes was not fully separated
    • Recruitment specificity to Notch1 versus other loci not defined
  6. 2013 High

    Identification of a 30-aa lncRNA-binding region showed that noncoding RNAs (e.g., Meg3) stimulate JARID2-EZH2 interaction and PRC2 recruitment, providing one mechanism for locus-specific targeting.

    Evidence Native and cross-linked RIP, in vitro JARID2-EZH2 interaction ± lncRNA, ChIP in MEG3-null cells

    PMID:24374312

    Open questions at the time
    • Sequence/structural determinants of RNA selectivity not defined
    • How RNA binding is coordinated with histone-mark reading unknown
  7. 2014 High

    JARID2 was identified as the mediator of Xist-induced PRC2 targeting to the inactive X, demonstrating RNA-guided, PRC2-independent recruitment chromosome-wide.

    Evidence RNA FISH, ChIP-seq, Jarid2 deletion, N-terminal domain mapping in an inducible XCI system

    PMID:24462204

    Open questions at the time
    • Direct Xist-JARID2 contact not biochemically resolved
    • How Xist repeats engage the N-terminal domain structurally unknown
  8. 2015 High

    JARID2 was shown to be methylated by EZH2 and read by EED, allosterically activating PRC2—resolving the recruitment-versus-activity paradox by revealing a positive feedback loop seeding H3K27me3 de novo.

    Evidence In vitro methylation, mass spectrometry site identification, EED binding and allosteric activation assays, differentiation H3K27me3 ChIP

    PMID:25620564

    Open questions at the time
    • Kinetics of methylation versus recruitment in vivo not measured
    • How the feedback loop is restricted to correct loci unclear
  9. 2016 High

    A ubiquitin interaction motif was found to bind H2AK119ub1, defining a direct chromatin-mark-reading mechanism that couples PRC1-deposited ubiquitin to PRC2 localization.

    Evidence Sequence-based UIM identification, in vitro ubiquitin binding, Co-IP, ChIP under H2AK119ub1 manipulation, UIM mutagenesis

    PMID:27892467

    Open questions at the time
    • Relative contribution of UIM versus lncRNA recruitment in vivo not quantified
    • Structural geometry of UIM-ubiquitin engagement not yet shown
  10. 2018 High

    Cryo-EM structures provided the physical basis for JARID2 stimulation of PRC2, showing methylated JARID2 mimics a methyl-H3 tail and stabilizes the active complex with AEBP2.

    Evidence Cryo-EM of human PRC2 with JARID2 and AEBP2, functional validation of cofactor interactions

    PMID:29348366

    Open questions at the time
    • Structure lacked a nucleosome substrate
    • Did not resolve the H2AK119ub1-bound configuration
  11. 2021 High

    A nucleosome-bound cryo-EM structure unified the recruitment and activation mechanisms, showing JARID2 contacts both EED and H2AK119-ubiquitin and helps overcome inhibitory active marks.

    Evidence Cryo-EM with designer H2AK119ub1 nucleosomes, in vitro PRC2 activity assays

    PMID:31479253 PMID:33479123

    Open questions at the time
    • In vivo relevance of overriding H3K4me3/H3K36me3 inhibition not directly tested
    • Role of JARID2 phosphorylation in this geometry not structurally resolved
  12. 2018 Medium

    JARID2 was shown to act through non-PRC2 routes—partnering with NuRD and existing as a cleaved ΔN-JARID2 in committed cells—revealing that its function is context-dependent and not strictly PRC2-bound.

    Evidence Western blot size determination, keratinocyte knockout with ΔN-JARID2 rescue, RNA-seq; immunoaffinity MS, Co-IP, GST pull-down, ChIP-reChIP for NuRD

    PMID:30573669 PMID:37658635

    Open questions at the time
    • Protease generating ΔN-JARID2 not identified
    • How ΔN-JARID2 activates differentiation genes mechanistically unknown
  13. 2025 Medium

    Comparison of Jarid2 versus Ezh2 loss in hematopoietic progenitors indicated PRC2-independent control of self-renewal and lineage output, distinguishing JARID2's regulatory roles from core PRC2.

    Evidence Conditional KO comparison, single-cell transcriptomics, competitive transplantation, human HSPC assays (preprint)

    PMID:40791535

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Molecular basis of STAT1/MHC-II upregulation by JARID2 loss not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How JARID2's distinct recruitment modes (H2AK119ub1, lncRNA, sequence-specific factors) and its PRC2-independent partnerships (G9a/GLP, SETDB1, NuRD, ΔN-JARID2) are selected and balanced across cell types remains unresolved.
  • No unified model integrating ubiquitin-reading, RNA-bridging, and methylation feedback at single loci
  • Determinants switching JARID2 between PRC2 and H3K9/NuRD complexes unknown
  • Identity and regulation of the ΔN-JARID2 cleavage event undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0003723 RNA binding 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0140110 transcription regulator activity 2 GO:0042393 histone binding 1
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
AEBP2EEDEZH2G9AGLPMTF2SETDB1SUZ12
Complex memberships
G9a/GLP (H3K9 methyltransferase complex)NuRDPRC2SETDB1 complex

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 JARID2 forms a stable complex with PRC2 (containing EZH2, SUZ12, EED) in ES cells, is required for PRC2 binding to >90% of PcG target genes genome-wide, and is sufficient to recruit PcG proteins to a heterologous promoter; inhibition of JARID2 causes major loss of PRC2 binding and reduction of H3K27me3 at target genes. Co-immunoprecipitation, genome-wide ChIP-seq, heterologous promoter recruitment assay, shRNA knockdown with H3K27me3 ChIP Nature High 20075857
2009 Jarid2 is a PRC2 subunit in ES cells that promotes PRC2 recruitment to target genes while simultaneously inhibiting PRC2 histone methyltransferase activity in vitro, acting as a 'molecular rheostat' that calibrates PRC2 function at developmental genes. Co-IP to establish PRC2 subunit status, genome-wide ChIP-seq (Jarid2, Ezh2, Suz12), in vitro histone methyltransferase activity assay with and without Jarid2, Xenopus knockdown Cell High 20064375
2010 Jarid2 is a novel subunit of PRC2 required for co-recruitment of PRC1 and RNA Polymerase II (Ser5-phosphorylated) to developmental genes in ES cells; Jarid2-deficient ES cells show reduced H3K4me2/me3 and H3K27me3 marking and loss of PRC1/PRC2 occupancy. ChIP-seq, ChIP-PCR, genetic knockout (Jarid2-deficient ES cells), immunofluorescence Nature cell biology High 20473294
2015 JARID2 is methylated by PRC2 (EZH2); this methylation is recognized by the EED subunit of PRC2 and triggers allosteric activation of PRC2 enzymatic activity. Jarid2 methylation promotes PRC2 activity at loci devoid of H3K27me3 and is required for correct H3K27me3 deposition during cell differentiation. In vitro methylation assay, mass spectrometry identification of methylated residue, EED binding assay, allosteric activation assay, cell differentiation H3K27me3 ChIP Molecular cell High 25620564
2016 Jarid2 contains a ubiquitin interaction motif (UIM) at its amino-terminus that directly binds mono-ubiquitylated H2A lysine 119 (H2AK119u1), mediating PRC2 localization to H2AK119u1-marked chromatin both in vitro and in vivo, thereby linking PRC1 and PRC2 activities. Identification of UIM by sequence analysis, in vitro ubiquitin binding assay, Co-IP, ChIP in cells with H2AK119u1 manipulation Nature communications High 27892467
2018 Cryo-EM structures of human PRC2 with cofactors JARID2 and AEBP2 show that methylated JARID2 mimics a methylated H3 tail to stimulate PRC2 activity; AEBP2 interacts with RBAP48 mimicking an unmodified H3 tail; SUZ12 interacts with all other subunits and stabilizes the complex. Cryo-electron microscopy structure determination, functional validation of cofactor interactions Science (New York, N.Y.) High 29348366
2021 Cryo-EM structure of PRC2 with JARID2 and AEBP2 bound to an H2AK119ub1-containing nucleosome reveals that JARID2 and AEBP2 each interact with one ubiquitin and the H2A-H2B surface; JARID2 stimulates PRC2 through interactions with both EED and H2AK119-ubiquitin; the presence of these cofactors partially overcomes inhibitory effects of H3K4me3 and H3K36me3 on core PRC2. Cryo-electron microscopy with designer nucleosome substrates, in vitro PRC2 activity assays Science (New York, N.Y.) High 33479123
2013 A 30-amino-acid region of JARID2 mediates interactions with long noncoding RNAs (lncRNAs); lncRNA presence stimulates JARID2-EZH2 interactions in vitro and JARID2-mediated PRC2 recruitment to chromatin in vivo. The lncRNA Meg3 (from Dlk1-Dio3 locus) interacts with PRC2 via JARID2, and loss of MEG3 alters JARID2, PRC2, and H3K27me3 chromatin distribution. RNA immunoprecipitation (native and cross-linked), in vitro JARID2-EZH2 interaction assay with/without lncRNA, ChIP in cells lacking MEG3 Molecular cell High 24374312
2014 Jarid2 is an important mediator of Xist-induced PRC2 targeting to the inactive X chromosome during X-chromosome inactivation. The B and F repeats of Xist RNA are critical for Jarid2 recruitment via its unique N-terminal domain; Xist-induced Jarid2 recruitment occurs chromosome-wide independently of functional PRC2, and Jarid2 loss prevents efficient PRC2 and H3K27me3 enrichment on Xist-coated chromatin. RNA FISH, ChIP-seq, genetic deletion of Jarid2, domain mapping by N-terminal deletion constructs, inducible XCI system Molecular cell High 24462204
2011 PRC2 in mouse ES cells contains at least three additional subunits beyond HeLa-defined composition: JARID2, MTF2, and esPRC2p48. JARID2, MTF2, and esPRC2p48 together (but not individually) synergistically stimulate PRC2 histone methyltransferase activity in vitro and enhance Oct4/Sox2/Klf4-mediated reprogramming. Mass spectrometry of PRC2 purified from ES cells, in vitro HMT assay with reconstituted complexes, shRNA knockdown, iPSC reprogramming assay Stem cells (Dayton, Ohio) High 21732481
2008 Jmj (Jarid2) represses cyclin D1 transcription through a protein complex with histone H3-K9 methyltransferases G9a and GLP; Jmj binds the cyclin D1 promoter and recruits G9a and GLP to increase H3-K9 methylation. Inactivation of both G9a and GLP (but not G9a alone) abolishes Jmj-mediated H3-K9 methylation and cyclin D1 repression. Co-immunoprecipitation (Jmj-G9a, Jmj-GLP), in vitro HMT assay, ChIP at cyclin D1 promoter, double-knockdown epistasis (G9a and GLP) The Journal of biological chemistry High 19010785
2012 Drosophila Jarid2 physically associates with all canonical PRC2 components (conserved with mammals), and loss-of-function of Jarid2 in flies selectively affects H3K27 methylation (among several histone modifications tested) without affecting other marks, confirming Jarid2 as a conserved PRC2 interactor that specifically regulates H3K27me3. Affinity purification of Drosophila Jarid2 and mass spectrometry, genetic mutant analysis with histone modification antibodies, genome-wide ChIP-seq (Jarid2, Su(z)12, H3K27me3) Molecular and cellular biology High 22354997
2019 JARID2 overrides geometrically defined preferences of core PRC2 for propagating H3K27 methylation on designer chromatin substrates and promotes de novo deposition of H3K27me3. Phosphorylation of JARID2 can partially regulate its ability to stimulate PRC2 activity. In vitro HMT assays with designer chromatin substrates (semisynthetic nucleosome arrays), phosphorylation assays Journal of the American Chemical Society High 31479253
2011 Endothelial-specific deletion of Jarid2 (using Cre-loxP) recapitulates cardiac hypertrabeculation and ventricular noncompaction observed in whole-body Jarid2 knockouts; Jarid2 occupies the Notch1 genomic locus (ChIP) and its deletion leads to increased endocardial Notch1 expression and downstream Notch signaling. Conditional knockout (tissue-specific Cre-loxP), microarray, quantitative ChIP at Notch1 locus, Notch signaling pathway analysis The Journal of biological chemistry High 21402699
2011 Jarid2 interacts with SETDB1 (a H3K9 methyltransferase) as identified by yeast two-hybrid and confirmed by co-immunoprecipitation; Jarid2 deletion reduces H3K9 methylation at the Notch1 locus in embryonic hearts and reduces SETDB1 accumulation at sites of Jarid2 occupancy. Yeast two-hybrid screen, co-immunoprecipitation, ChIP at Notch1 locus in KO vs. WT hearts, genome-wide ChIP-chip for H3K9me targets The Journal of biological chemistry High 22110129
2013 IFN-γ/CIITA signaling induces sequential recruitment of JARID2 and then PRC2 to muscle gene promoters; CIITA first interacts with JARID2, causing RNA Pol II (Ser5-phosphorylated) to pause, then additional PRC2 subunits including EZH2 are recruited in a JARID2-dependent manner, concurrent with H3K27 methylation and repression of myogenic genes. Co-immunoprecipitation (CIITA-JARID2), ChIP (sequential recruitment), gene expression analysis, JARID2-dependent rescue experiments Science signaling High 24327761
2014 Jarid2 is upregulated by TCR signaling and during positive selection in the thymus; Jarid2 binds the Zbtb16 (PLZF) locus and its loss increases PLZF expression with decreased H3K9me3 at this locus, controlling iNKT cell maturation. Jarid2 is reported as a component of three lysine methyltransferase complexes: PRC2 (H3K27), GLP-G9a (H3K9), and SETDB1 (H3K9). ChIP at Zbtb16/PLZF locus, genetic knockout (T cell-specific), flow cytometry, H3K9me3 and H3K27me3 ChIP Nature communications Medium 25105474
2011 Deletion of Jarid2 in mouse epidermis reduces proliferation and potentiates differentiation of postnatal epidermal progenitors; Jarid2 deficiency reduces H3K27me3 at PRC2-target epidermal differentiation genes in neonatal epidermis, and causes delayed hair follicle cycling due to decreased proliferation of HF stem cells. Conditional knockout (epidermis-specific), H3K27me3 ChIP, BrdU proliferation assay, histological analysis The EMBO journal High 21811233
2013 JARID2 is a direct transcriptional target of the PAX3-FOXO1 fusion protein; JARID2 silencing induces myogenic differentiation (increased MYOG, MYL1 expression); JARID2 binds the MYOG and MYL1 promoters and alters H3K27me3 there in an EED-dependent manner. ChIP at MYOG/MYL1 promoters, luciferase reporter for PAX3-FOXO1 direct targeting, siRNA knockdown, overexpression rescue Oncogene Medium 23435416
2011 Jarid2-cyclin D1 genetic epistasis in mouse cardiomyocytes: Jmj/cyclin D1 double-mutant mice show that Jmj is required for normal cardiomyocyte differentiation and GATA4 protein expression through repression of cyclin D1. CDK4 (activated by cyclin D1) phosphorylates GATA4 directly, promoting its degradation in cultured cells. Double-mutant mouse genetics (Jmj/cyclin D1), transgenic overexpression, in vitro kinase assay (CDK4 phosphorylation of GATA4), rescue by exogenous GATA4 Development (Cambridge, England) High 21447557
2015 JARID2 and the PRC2 complex regulate skeletal muscle differentiation by directly repressing the Wnt antagonist SFRP1; depletion of JARID2 causes upregulation of SFRP1, which blocks MYOD and β-catenin nuclear translocation required for differentiation. ChIP confirmed JARID2 and EZH2 occupancy and H3K27me3 at the SFRP1 locus. ChIP-seq, ChIP-PCR (JARID2, EZH2, H3K27me3 at SFRP1), shRNA depletion, Wnt pathway rescue (β-catenin nuclear translocation), ectopic SFRP1 expression Epigenetics & chromatin High 30119689
2019 JARID2 and the PRC2 complex regulate the skeletal muscle cell cycle by directly repressing cyclin D1 and cyclin E1 (targets of PRC2-mediated H3K27me3) and repressing RB1; depletion of JARID2 increases proliferation and S-phase accumulation. Ectopic RB1 expression can suppress cyclin D1 in JARID2-depleted cells. ChIP at cyclin D1, cyclin E1, and RB1 promoters; shRNA stable depletion; flow cytometry cell cycle analysis; ectopic expression rescue The Journal of biological chemistry Medium 31578284
2007 Jarid2 physically and functionally interacts with zinc finger protein Zfp496 (identified by yeast two-hybrid); Zfp496 functions as a transcriptional activator and inhibits Jarid2-mediated transcriptional repression, while Jarid2 represses Zfp496-mediated transcriptional activation. Yeast two-hybrid screening, co-immunoprecipitation, transcriptional reporter assays FEBS letters Medium 17521633
2010 Nkx2.5 directly regulates Jarid2 expression in second heart field progenitors; Nkx2.5 occupies consensus binding sites in the Jarid2 promoter (ChIP), and Nkx2.5 overexpression down-regulates Jarid2 promoter activity and mRNA levels. ChIP at Jarid2 promoter in pharyngeal arch cells, promoter-luciferase reporter assay, overexpression Developmental dynamics Medium 20549724
2015 Jarid2 inhibition of JARID2 in hematopoietic stem and progenitor cells (HSPCs) enhances competitive transplantation capacity in mice (similar to Suz12 depletion); JARID2 depletion enhances in vitro expansion and in vivo reconstitution of human HSPCs. Gene expression profiling identified common Suz12 and Jarid2 target genes enriched for H3K27me3. Competitive bone marrow transplantation, shRNA knockdown, human HSPC expansion assay, gene expression profiling, H3K27me3 ChIP Blood Medium 25645357
2015 JARID2 promotes iPSC reprogramming by suppressing Arf expression (a known reprogramming barrier); the N-terminal half of JARID2 is sufficient for this promotion. JARID2 physically interacts with ESRRB, SALL4A, and PRDM14, and these JARID2-associated proteins synergistically facilitate iPSC reprogramming in a JARID2-dependent manner. JARID2 also accelerates silencing of retroviral Klf4 transgene and demethylation of the Nanog promoter. Co-immunoprecipitation (JARID2-ESRRB, JARID2-SALL4A, JARID2-PRDM14), N-terminal deletion mapping, iPSC reprogramming efficiency assay, bisulfite sequencing (Nanog promoter), domain rescue experiments Stem cells (Dayton, Ohio) Medium 26523946
2018 In lineage-committed human keratinocytes (unlike ES cells), JARID2 predominantly exists as a novel low-molecular-weight form (ΔN-JARID2) lacking the N-terminal PRC2-interacting domain, generated by proteolytic cleavage. ΔN-JARID2 (lacking PRC2 interaction) can rescue repression of epidermal differentiation genes in JARID2-null keratinocytes, suggesting a PRC2-independent function in promoting differentiation gene activation. Western blotting (size determination), JARID2 knockout (keratinocytes), rescue by ΔN-JARID2 expression, RNA-seq of JARID2-null cells The EMBO journal Medium 30573669
2015 Jarid2-deficient ES cells express constitutively high levels of Nanog and reduced PCP signaling components (Wnt9a, Prickle1, Fzd2) and lowered β-catenin activity; depletion of Wnt9a/Prickle1/Fzd2 or overexpression of Nanog phenocopies Jarid2-deficient differentiation block. Co-culture of Jarid2-/- with wild-type ESCs restores variable Nanog expression and β-catenin activity. Genetic knockout, gene expression profiling, Nanog overexpression rescue, co-culture experiments, blastocyst injection Cell reports Medium 26190104
2014 JARID2 is involved in TGF-β-induced epithelial-mesenchymal transition; ChIP assays showed JARID2 is recruited to CDH1 and miR-200 family gene regulatory regions during TGF-β treatment, where it regulates H3K27me3 levels and EZH2 occupancy to mediate transcriptional repression of these EMT-suppressor genes. ChIP (JARID2, EZH2, H3K27me3 at CDH1 and miR-200 loci), siRNA knockdown, TGF-β treatment, gene expression analysis PloS one Medium 25542019
2016 JARID2 promotes HCC invasion and metastasis by repressing PTEN expression through increasing H3K27me3 at the PTEN promoter, which activates AKT and enhances EMT. ChIP at PTEN promoter (H3K27me3), siRNA knockdown and overexpression, in vitro invasion/migration assays, xenograft metastasis model Oncotarget Medium 27259236
2015 JARID2 negatively regulates CCND1 (cyclin D1) expression in leukemia cells by increasing H3K27 trimethylation at the CCND1 promoter; knockdown of JARID2 promotes G1/S transition and proliferation, while ectopic JARID2 expression inhibits these phenotypes. ChIP (JARID2 and H3K27me3 at CCND1 promoter), siRNA knockdown, ectopic overexpression, flow cytometry cell cycle analysis International journal of hematology Medium 25939703
2017 Jarid2 is required for late-stage differentiation of embryonic pancreatic β-cells; conditional ablation in pancreatic progenitors reduces endocrine cell area and impairs β-cell differentiation program. Jarid2-deficient pancreases show impaired deposition of RNAPII-Ser5P (initiating Pol II) but no changes in H3K27me3 at affected endocrine gene promoters, indicating a PRC2-independent mechanism. Conditional knockout (pancreas-specific Cre), genome-wide expression analysis, ChIP (H3K27me3 and RNAPII-Ser5P at endocrine gene promoters) Scientific reports Medium 28912479
2023 Jarid2 regulates the transition from early to late retinal progenitor competence by maintaining H3K27me3 repression of Foxp1; loss of Jarid2 reduces H3K27me3 on Foxp1 and other early progenitor genes, leading to extended production of early-born cell types. Foxp1 is required for extending early retinal cell production after Jarid2 loss (genetic epistasis). Conditional knockout (retinal progenitor), ChIP (H3K27me3 at Foxp1 and early progenitor gene loci), genetic epistasis (Jarid2/Foxp1 double manipulation), birthdating assays Cell reports Medium 36924502
2019 Jarid2 mediates H3K27me3-dependent repression of p16 in bladder cancer tumor-initiating cells; knockdown of Jarid2 upregulates p16 with increased H3K27me3 at the p16 promoter region, and reduces sphere-forming capacity and tumorigenicity of bladder cancer TICs in vivo. ChIP at p16 promoter, siRNA knockdown, sphere formation assay, in vivo tumorigenicity assay Life sciences Low 31125562
2019 Myocardial-specific ablation of Jarid2 (αMHC::Cre) causes dilated cardiomyopathy and premature death; Jarid2 is required to repress fetal contractile genes (Tnni1, Acta2) in neonatal stages through ErbB4 signaling, and its loss prevents normal induction of adult contractile gene expression. Conditional knockout (αMHC-Cre), gene expression profiling, pathway analysis, ErbB4 signaling analysis The Journal of biological chemistry Medium 30700554
2018 Deletion of Jarid2 by Nkx2.5-Cre (cardiac progenitors) causes ventricular septal defects, thin myocardium, hypertrabeculation, and neonatal lethality; Jarid2 is required for PRC2 occupancy and H3K27me3 at the Isl1 promoter in the myocardium, and its deletion elevates Isl1, Bmp10, and neural gene expression. Conditional knockout (Nkx2.5-Cre), ChIP (H3K27me3 and PRC2 at Isl1 promoter), genome-wide ChIP-seq, gene expression analysis The Journal of biological chemistry Medium 29891551
2025 JARID2 knockdown in mouse multipotent progenitors enhances T-cell output (distinct from EZH2 loss which increases myeloid differentiation), suggesting JARID2 has PRC2-independent functions in hematopoiesis; mechanistically, JARID2 knockdown in human UCB HSPCs promotes a quiescent long-term self-renewal gene expression program via upregulation of STAT1 and MHC class II immunophenotype, conferring HSC-like potential to human MPPs in vivo. Genetic comparison of Jarid2 vs. Ezh2 conditional KO, single-cell transcriptomics, competitive transplantation, human HSPC functional assays in vivo bioRxivpreprint Medium 40791535
2016 In Drosophila spermatogenesis, dJmj (Jarid2) localizes exclusively to the nucleolus at late growth stage in a Polycomb-dependent manner; Polycomb (Pc) interacts with dJmj at the nucleolus (confirmed by Proximity Ligation Assay), and tTAF is responsible for Pc-mediated recruitment of dJmj to the nucleolus. H3K27me3 levels decrease in nuclei at this stage, correlating with nucleolar sequestration of dJmj. Immunocytochemistry, Duolink In Situ Proximity Ligation Assay (Pc-dJmj interaction), PcG mutant analysis, tTAF mutant analysis Spermatogenesis Low 28144496
2023 JARID2 physically interacts with the NuRD complex (identified by immunoaffinity purification and silver staining mass spectrometry, confirmed by Co-IP and GST pull-down) in breast cancer cells; JARID2-NuRD co-occupies and represses tumor suppressor genes BRCA2, RB1, and INPP4B (confirmed by ChIP-seq and ChIP-reChIP assays). Immunoaffinity purification + mass spectrometry, Co-IP, GST pull-down, ChIP-seq, ChIP-PCR, ChIP-reChIP Cancer communications (London, England) Medium 37658635

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 JARID2 regulates binding of the Polycomb repressive complex 2 to target genes in ES cells. Nature 458 20075857
2009 Jarid2/Jumonji coordinates control of PRC2 enzymatic activity and target gene occupancy in pluripotent cells. Cell 444 20064375
2013 Interactions between JARID2 and noncoding RNAs regulate PRC2 recruitment to chromatin. Molecular cell 308 24374312
2010 Jarid2 is a PRC2 component in embryonic stem cells required for multi-lineage differentiation and recruitment of PRC1 and RNA Polymerase II to developmental regulators. Nature cell biology 256 20473294
2015 Jarid2 Methylation via the PRC2 Complex Regulates H3K27me3 Deposition during Cell Differentiation. Molecular cell 226 25620564
2016 Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2. Nature communications 223 27892467
2014 Jarid2 Is Implicated in the Initial Xist-Induced Targeting of PRC2 to the Inactive X Chromosome. Molecular cell 209 24462204
2021 JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1 and other histone modifications. Science (New York, N.Y.) 197 33479123
2018 Structures of human PRC2 with its cofactors AEBP2 and JARID2. Science (New York, N.Y.) 168 29348366
2011 PRC2 complexes with JARID2, MTF2, and esPRC2p48 in ES cells to modulate ES cell pluripotency and somatic cell reprogramming. Stem cells (Dayton, Ohio) 127 21732481
2014 miRNA-mRNA integrative analysis in primary myelofibrosis CD34+ cells: role of miR-155/JARID2 axis in abnormal megakaryopoiesis. Blood 105 25097177
2011 Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies. American journal of hematology 91 22190018
2013 JARID2 is a direct target of the PAX3-FOXO1 fusion protein and inhibits myogenic differentiation of rhabdomyosarcoma cells. Oncogene 84 23435416
2009 Reticuloendotheliosis virus strain T induces miR-155, which targets JARID2 and promotes cell survival. Journal of virology 83 19759154
2010 Inactive yet indispensable: the tale of Jarid2. Trends in cell biology 78 21074441
2011 Jarid2 regulates mouse epidermal stem cell activation and differentiation. The EMBO journal 64 21811233
2008 A jumonji (Jarid2) protein complex represses cyclin D1 expression by methylation of histone H3-K9. The Journal of biological chemistry 64 19010785
2012 Polycomb repressive complex 2-dependent and -independent functions of Jarid2 in transcriptional regulation in Drosophila. Molecular and cellular biology 63 22354997
2011 Endothelial Jarid2/Jumonji is required for normal cardiac development and proper Notch1 expression. The Journal of biological chemistry 62 21402699
2014 JARID2 is involved in transforming growth factor-beta-induced epithelial-mesenchymal transition of lung and colon cancer cell lines. PloS one 60 25542019
2019 Dihydroartemisinin inhibits prostate cancer via JARID2/miR-7/miR-34a-dependent downregulation of Axl. Oncogenesis 59 30783079
2011 Jarid2 (Jumonji, AT rich interactive domain 2) regulates NOTCH1 expression via histone modification in the developing heart. The Journal of biological chemistry 59 22110129
2020 miR-155 antagomir protect against DSS-induced colitis in mice through regulating Th17/Treg cell balance by Jarid2/Wnt/β-catenin. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 53 32135463
2010 The JARID2-PRC2 duality. Genes & development 52 20439426
2015 miRNA-204 drives cardiomyocyte proliferation via targeting Jarid2. International journal of cardiology 48 26298346
2015 Jarid2 regulates hematopoietic stem cell function by acting with polycomb repressive complex 2. Blood 47 25645357
2011 Coordinated regulation of differentiation and proliferation of embryonic cardiomyocytes by a jumonji (Jarid2)-cyclin D1 pathway. Development (Cambridge, England) 47 21447557
2015 Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development. Cell reports 46 26190104
2016 JARID2 promotes invasion and metastasis of hepatocellular carcinoma by facilitating epithelial-mesenchymal transition through PTEN/AKT signaling. Oncotarget 41 27259236
2010 Jarid2 is among a set of genes differentially regulated by Nkx2.5 during outflow tract morphogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 40 20549724
2013 Interferon-γ resets muscle cell fate by stimulating the sequential recruitment of JARID2 and PRC2 to promoters to repress myogenesis. Science signaling 38 24327761
2014 Jarid2 is induced by TCR signalling and controls iNKT cell maturation. Nature communications 36 25105474
2012 Immune function genes CD99L2, JARID2 and TPO show association with autism spectrum disorder. Molecular autism 34 22681640
2009 Whole genome association study in a homogenous population in Shandong peninsula of China reveals JARID2 as a susceptibility gene for schizophrenia. Journal of biomedicine & biotechnology 32 19884986
2022 Human bone marrow-mesenchymal stem cell-derived exosomal microRNA-188 reduces bronchial smooth muscle cell proliferation in asthma through suppressing the JARID2/Wnt/β-catenin axis. Cell cycle (Georgetown, Tex.) 31 34974799
2018 JARID2 and the PRC2 complex regulate skeletal muscle differentiation through regulation of canonical Wnt signaling. Epigenetics & chromatin 30 30119689
2007 Positive association of schizophrenia to JARID2 gene. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 29 16967465
2023 Jarid2 promotes temporal progression of retinal progenitors via repression of Foxp1. Cell reports 28 36924502
2015 JARID2 inhibits leukemia cell proliferation by regulating CCND1 expression. International journal of hematology 28 25939703
2018 Cardiac-specific developmental and epigenetic functions of Jarid2 during embryonic development. The Journal of biological chemistry 27 29891551
2014 Temperature influences histone methylation and mRNA expression of the Jmj-C histone-demethylase orthologues during the early development of the oyster Crassostrea gigas. Marine genomics 27 25224965
2007 Characterization of zinc finger protein 496 that interacts with Jumonji/Jarid2. FEBS letters 26 17521633
2019 JARID2 and the PRC2 complex regulate the cell cycle in skeletal muscle. The Journal of biological chemistry 25 31578284
2018 A novel form of JARID2 is required for differentiation in lineage-committed cells. The EMBO journal 25 30573669
2019 Jarid2 enhances the progression of bladder cancer through regulating PTEN/AKT signaling. Life sciences 24 31125562
2019 Nucleation and Propagation of Heterochromatin by the Histone Methyltransferase PRC2: Geometric Constraints and Impact of the Regulatory Subunit JARID2. Journal of the American Chemical Society 23 31479253
2013 Haploinsufficiency of two histone modifier genes on 6p22.3, ATXN1 and JARID2, is associated with intellectual disability. Orphanet journal of rare diseases 23 23294540
2022 LINC01021 maintains tumorigenicity by enhancing N6-methyladenosine reader IMP2 dependent stabilization of MSX1 and JARID2: implication in colorectal cancer. Oncogene 22 35173309
2020 JARID2 haploinsufficiency is associated with a clinically distinct neurodevelopmental syndrome. Genetics in medicine : official journal of the American College of Medical Genetics 22 33077894
2020 Genome-wide analysis of JMJ-C histone demethylase family involved in salt-tolerance in Gossypium hirsutum L. Plant physiology and biochemistry : PPB 21 33257231
2016 Brazilian multicenter study of association between polymorphisms in CRISPLD2 and JARID2 and non-syndromic oral clefts. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 20 27328068
2015 Combined Overexpression of JARID2, PRDM14, ESRRB, and SALL4A Dramatically Improves Efficiency and Kinetics of Reprogramming to Induced Pluripotent Stem Cells. Stem cells (Dayton, Ohio) 20 26523946
2014 RETRACTED: The downregulation of GFI1 by the EZH2-NDY1/KDM2B-JARID2 axis and by human cytomegalovirus (HCMV) associated factors allows the activation of the HCMV major IE promoter and the transition to productive infection. PLoS pathogens 20 24830456
2023 JARID2 coordinates with the NuRD complex to facilitate breast tumorigenesis through response to adipocyte-derived leptin. Cancer communications (London, England) 19 37658635
2017 Knockdown of JARID2 inhibits the proliferation and invasion of ovarian cancer through the PI3K/Akt signaling pathway. Molecular medicine reports 19 28765957
2008 Induction by left ventricular overload and left ventricular failure of the human Jumonji gene (JARID2) encoding a protein that regulates transcription and reexpression of a protective fetal program. The Journal of thoracic and cardiovascular surgery 19 18805276
2014 The Jumonji gene family in Crassostrea gigas suggests evolutionary conservation of Jmj-C histone demethylases orthologues in the oyster gametogenesis and development. Gene 18 24406622
2017 Etv2-miR-130a-Jarid2 cascade regulates vascular patterning during embryogenesis. PloS one 17 29232705
2010 Expression and association data strongly support JARID2 involvement in nonsyndromic cleft lip with or without cleft palate. Human mutation 17 20506229
2017 Jarid2 is essential for the maintenance of tumor initiating cells in bladder cancer. Oncotarget 16 28445934
2023 JARID2 and EZH2, the eminent epigenetic drivers in human cancer. Gene 15 37353042
2018 MiR-155 inhibition ameliorates 2, 4, 6-Trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis in rat via influencing the differentiation of Th17 cells by Jarid2. International immunopharmacology 15 30253332
2022 DNA Methylation Signature for JARID2-Neurodevelopmental Syndrome. International journal of molecular sciences 14 35887345
2021 JARID2 promotes stemness and cisplatin resistance in non-small cell lung cancer via upregulation of Notch1. The international journal of biochemistry & cell biology 14 34246759
2017 Late-stage differentiation of embryonic pancreatic β-cells requires Jarid2. Scientific reports 14 28912479
2017 Function of JARID2 in bovines during early embryonic development. PeerJ 14 29302400
2018 Inducible CRISPR genome editing platform in naive human embryonic stem cells reveals JARID2 function in self-renewal. Cell cycle (Georgetown, Tex.) 12 29466914
2022 The LINC00852/miR-29a-3p/JARID2 axis regulates the proliferation and invasion of prostate cancer cell. BMC cancer 11 36471281
2021 MiR-22 regulated T cell differentiation and hepatocellular carcinoma growth by directly targeting Jarid2. American journal of cancer research 9 34094675
2021 The function and mechanism of the JARID2/CCND1 axis in modulating glioma cell growth and sensitivity to temozolomide (TMZ). Cancer biology & therapy 9 34251962
2023 JARID2 regulates epithelial mesenchymal transition through the PTEN/AKT signalling pathways in ovarian endometriosis. Reproductive biology 8 36640627
2023 Genome-wide identification and expression analysis of the JMJ-C gene family in melon (Cucumis melo L.) reveals their potential role in fruit development. BMC genomics 8 38093236
2021 LINC00649 Facilitates the Cellular Process of Bladder Cancer Cells via Signaling Axis miR-16-5p/JARID2. Urologia internationalis 8 33789312
2016 Reduced Expression of Jumonji AT-Rich Interactive Domain 2 (JARID2) in Glioma Inhibits Tumor Growth In Vitro and In Vivo. Oncology research 8 27641964
2023 Functional Insight into and Refinement of the Genomic Boundaries of the JARID2-Neurodevelopmental Disorder Episignature. International journal of molecular sciences 7 37762546
2022 Phenotypic expansion and variable expressivity in individuals with JARID2-related intellectual disability: A case series. Clinical genetics 7 35533077
2017 Knockdown of JARID2 inhibits the viability and migration of placenta trophoblast cells in preeclampsia. Molecular medicine reports 7 28714012
2020 Promoting role of circ-Jarid2/miR-129-5p/Celf1 axis in cardiac hypertrophy. Gene therapy 6 32632266
2019 Myocardial-specific ablation of Jumonji and AT-rich interaction domain-containing 2 (Jarid2) leads to dilated cardiomyopathy in mice. The Journal of biological chemistry 6 30700554
2014 Jarid2 links MicroRNA and chromatin in Th17 cells. Immunity 6 24950205
2014 Association of JARID2 polymorphisms with non-syndromic orofacial clefts in northern Chinese Han population. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 6 25155265
2024 Valproic acid regulates the miR-155/Jarid2 axis by affecting miR-155 promoter methylation in glioma. Acta biochimica et biophysica Sinica 5 38273784
2024 JARID2, a novel regulatory factor, promotes cell proliferation, migration, and invasion in oral squamous cell carcinoma. BMC cancer 4 38961353
2022 Distinct binding pattern of EZH2 and JARID2 on RNAs and DNAs in hepatocellular carcinoma development. Frontiers in oncology 4 36578923
2024 Genome-wide scan of Flortaucipir PET levels finds JARID2 associated with cerebral tau deposition. medRxiv : the preprint server for health sciences 3 39417126
2024 The neurodevelopmental regulatory role and clinical value of hsa-circ-CORO1C-hsa-miR-708-3p-JARID2 + LNPEP axis in early-onset schizophrenia. Schizophrenia (Heidelberg, Germany) 3 39702523
2022 A novel partial de novo duplication of JARID2 gene causing a neurodevelopmental phenotype. Molecular genetics & genomic medicine 3 35979655
2016 Polycomb-dependent nucleolus localization of Jumonji/Jarid2 during Drosophila spermatogenesis. Spermatogenesis 3 28144496
2023 A Functional Single Nucleotide Polymorphism in the 3' Untranslated Region of the Porcine JARID2 Gene Is Associated with Aggressive Behavior of Weaned Pigs after Mixing. International journal of molecular sciences 2 38203196
2026 miR-454-3p drives development of hepatic steatosis by negatively regulating JARID2. Biochemical pharmacology 1 41794262
2025 Functional Comparison to Ezh2 Reveals PRC2-Independent Functions of Jarid2 in Hematopoietic Stem Cell Lineage Commitment. bioRxiv : the preprint server for biology 1 40791535
2025 METTL3-mediated m6A modification of circCDKAL1 regulates macrophage M1 polarization and nasal epithelial cell barrier function in allergic rhinitis through IGF2BP2/JARID2/HMGB1 axis. Cell death discovery 1 40883266
2024 MiR-155 promotes compensatory lung growth by inhibiting JARID2 activation of CD34+ endothelial progenitor cells. PloS one 1 38394221
2024 JARID2 activation by NFYA promotes stemness of triple-negative breast cancer cells through the PI3K/AKT pathway. Expert review of anticancer therapy 1 39254227
2024 Association of HHV‑6 reactivation and SLC6A3 (C>T, rs40184), BDNF (C>T, rs6265), and JARID2 (G>A, rs9383046) single nucleotide polymorphisms in depression. Biomedical reports 1 39420919
2024 Jumonji and AT-Rich Interacting Domain 2 (JARID2) exhibits a tumor-suppressive role in Oral Squamous Cell Carcinoma by modulating tumor progression and metastasis. 3 Biotech 1 39619816
2023 Integrated bioinformatics and experimental validation reveal the role of JARID2 in ovarian cancer. Epigenomics 1 37309591
2022 Genetic determination and JARID2 over-expression in a thermal incubation experiment in Casque-Headed Lizard. PloS one 1 35797377
2025 JARID2 Inhibition Reprograms Human Hematopoietic Progenitor Cells To Enhance Bone Marrow Transplantation. bioRxiv : the preprint server for biology 0 40950155
2020 Autoregulation of JARID2 through PRC2 interaction with its antisense ncRNA. BMC research notes 0 33126912

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