Affinage

PHF2

Lysine-specific demethylase PHF2 · UniProt O75151

Length
1096 aa
Mass
120.8 kDa
Annotated
2026-06-10
34 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PHF2 is a Jumonji-C family histone demethylase that erases the repressive H3K9me2 mark at target gene promoters to activate transcription across diverse developmental and metabolic programs (PMID:21532585, PMID:29844386). Its catalytic Jumonji domain coordinates Fe2+ and α-ketoglutarate in an octahedral arrangement, but the isolated enzyme is intrinsically inactive on histone substrates and requires regulatory input — PKA-mediated phosphorylation licenses demethylation and assembly with the DNA-binding partner ARID5B (PMID:21532585, PMID:21167174), while AMPKα2 phosphorylation at Ser655 enhances H3K9me2 demethylase activity (PMID:36872368). Promoter targeting is achieved through a bivalent reader module in which the PHD finger and Jumonji domain together form a methyl-lysine aromatic cage that binds H3K4me3 with high affinity, coupling recognition of active chromatin to H3K9 demethylation (PMID:20129925, PMID:36596360). PHF2 is recruited to specific loci by sequence-specific transcription factors — ARID5B (including ARID5B–Sox9 complexes), C/EBPα/δ, ChREBP, and p53 — to selectively activate chondrogenic, adipogenic, lipogenic, and p53-target genes (PMID:24276541, PMID:25043306, PMID:25266703, PMID:29844386). Beyond gene activation, PHF2 has repressive and structural functions that are independent of its demethylase activity: it competes with PHF8 and recruits the methyltransferase SUV39H1 to silence rDNA transcription (PMID:25204660), and it associates with the cohesin subunit RAD21 to organize TAD boundaries, chromatin loops, and DNA replication origins, with cohesin loop extrusion translocating PHF2 across the genome (PMID:38808662, PMID:39748119). PHF2 functions as a guardian of genome stability, maintaining pericentromeric heterochromatin integrity, suppressing R-loop accumulation and DNA damage, and promoting CtIP/BRCA1-dependent homologous recombination repair (PMID:31488723, PMID:32232336, PMID:38890452). PHF2 additionally acts as an E3 ubiquitin ligase that ubiquitinates and destabilizes SREBP1c to restrain lipogenesis (PMID:37828054). Through these activities it controls neural progenitor proliferation, memory consolidation, myogenic and metabolic differentiation, and tumor and neuroinflammatory phenotypes (PMID:31488723, PMID:31359606, PMID:36872368, PMID:38701072, PMID:40849543).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2010 High

    Established how PHF2 is targeted to chromatin and linked H3K4me3 reading to H3K9 demethylase output, defining the basic reader–eraser cross-talk.

    Evidence X-ray crystallography of the PHD–H3K4me3 interaction with ChIP validation at rDNA promoters

    PMID:20129925

    Open questions at the time
    • Did not resolve why the isolated enzyme lacks robust catalytic activity
    • Promoter selectivity beyond rDNA not addressed
  2. 2010 High

    Defined the catalytic Jumonji active-site architecture and revealed that an atypical fifth metal ligand alone does not account for the enzyme's inactivity, predicting a requirement for additional regulatory factors.

    Evidence Crystal structures with/without metal, in vitro demethylase assay, and Y321H mutagenesis

    PMID:21167174

    Open questions at the time
    • The activating factor/modification was not identified in this study
    • No histone substrate turnover demonstrated in vitro
  3. 2011 High

    Resolved the activation paradox by showing PHF2 is inactive alone and requires PKA phosphorylation plus ARID5B partnership to demethylate target promoters.

    Evidence In vitro phosphorylation, Co-IP, ChIP, and cell-based demethylase assays

    PMID:21532585

    Open questions at the time
    • The specific PKA phosphosite was not defined
    • Mechanism by which phosphorylation activates catalysis unresolved
  4. 2013 High

    Showed PHF2 is recruited by transcription-factor complexes (ARID5B–Sox9) to drive a defined developmental program, establishing partner-directed promoter targeting in vivo.

    Evidence Reciprocal Co-IP, ChIP, Arid5b knockout mice, siRNA, and chondrocyte differentiation assays

    PMID:24276541

    Open questions at the time
    • Whether PHF2 phosphorylation status governs Sox9-target activation not tested
  5. 2014 High

    Extended partner-directed activation to multiple transcription factors (p53, C/EBPα/δ) and showed PHF2 is required for their downstream transcriptional output and phenotypes.

    Evidence Co-IP, ChIP, siRNA/shRNA knockdown, xenograft and adipocyte differentiation models

    PMID:25043306 PMID:25266703

    Open questions at the time
    • Adipogenic role rests on a single-lab Medium-confidence study
    • Direct vs indirect promoter binding not fully separated
  6. 2014 High

    Revealed a demethylase-independent repressive function, showing PHF2 can silence rDNA by competing with PHF8 and recruiting SUV39H1.

    Evidence RNAi, overexpression, ChIP, Pol I transcription assays, Co-IP, and catalytic-mutant dissection

    PMID:25204660

    Open questions at the time
    • How PHF2 toggles between activating and repressive modes at different loci is unresolved
  7. 2018 High

    Connected PHF2 demethylase activity to systemic lipid and oxidative-stress metabolism through ChREBP co-activation and Nrf2 target regulation.

    Evidence ChIP, mouse genetic models, siRNA, metabolic flux and lipidomic analyses

    PMID:29844386

    Open questions at the time
    • Upstream signal coupling metabolic state to PHF2 activity not defined here
  8. 2019 High

    Identified PHF2 as a genome-stability factor in neural progenitors that keeps replication/cell-cycle genes accessible and prevents R-loop-associated DNA damage.

    Evidence siRNA, genome-wide ChIP-seq, S9.6 R-loop staining, γH2AX, cell-cycle analysis, in vivo electroporation

    PMID:31488723

    Open questions at the time
    • Whether genome instability is a direct demethylase effect or secondary to transcriptional defects not fully separated
  9. 2020 High

    Showed PHF2 promotes homologous recombination repair by demethylase-dependent control of CtIP/BRCA1 expression and DSB resection.

    Evidence siRNA, IRIF immunofluorescence, HR reporter assay, RPA phosphorylation, PARPi sensitivity

    PMID:32232336

    Open questions at the time
    • Direct chromatin recruitment to break sites not demonstrated
  10. 2022 High

    Defined the structural basis of high-affinity methyl-lysine reading, showing PHD and Jumonji domains form a single bivalent aromatic cage rather than the PHD acting alone.

    Evidence X-ray crystallography and fluorescence polarization binding with H3 and VRK1 peptides

    PMID:36596360

    Open questions at the time
    • Functional consequence of VRK1-K4me3 binding not established
    • How bivalent reading couples to catalysis unresolved
  11. 2023 High

    Uncovered a non-demethylase enzymatic activity, defining PHF2 as an E3 ubiquitin ligase for SREBP1c that is itself regulated by ZDHHC23 palmitoylation-driven degradation.

    Evidence Co-IP, in vitro ubiquitination and palmitoylation assays, protein stability assays in hepatoma cells

    PMID:37828054

    Open questions at the time
    • Catalytic residues mediating ligase activity not mapped
    • Generality of E3 activity beyond SREBP1c unknown
  12. 2023 High

    Identified AMPKα2 phosphorylation at Ser655 as a defined activating modification that boosts H3K9me2 demethylation and suppresses metastasis, providing a kinase-to-chromatin axis.

    Evidence In vitro kinase assay, Co-IP, S655E/S655A mutagenesis, ChIP, and mouse metastasis model

    PMID:36872368

    Open questions at the time
    • Relationship between the AMPK Ser655 and earlier PKA phosphorylation events not reconciled
  13. 2024 High

    Established demethylase-independent structural roles, showing PHF2 partners with cohesin/RAD21 to set TAD boundaries, loops, and replication origins.

    Evidence Co-IP, ChIP-seq, Hi-C, replication origin mapping, CRISPR KO with catalytic-dead rescue in neural stem cells

    PMID:38808662

    Open questions at the time
    • Direct physical contact interface between PHF2 and cohesin not mapped
  14. 2024 High

    Showed PHF2 maintains pericentromeric heterochromatin and satellite silencing requiring both PHD and Jumonji domains, linking it to genome integrity at repeats.

    Evidence Mass-spec interactome, ChIP-seq, RNA-seq, immunofluorescence, CRISPR KO, domain-deletion mutants

    PMID:38890452

    Open questions at the time
    • How an H3K9me2 demethylase sustains H3K9me3-rich heterochromatin mechanistically unclear
  15. 2025 High

    Demonstrated that cohesin loop extrusion actively translocates PHF2 genome-wide and that the relationship is reciprocal, with PHF2 stabilizing cohesin at CTCF-independent TSSs.

    Evidence ChIP-seq, Co-IP, auxin-inducible cohesin/Wapl/CTCF depletion, and Hi-C

    PMID:39748119

    Open questions at the time
    • Molecular basis of PHF2 hand-off to cohesin not defined
  16. 2025 Medium

    Extended the AMPK–PHF2 axis to muscle stem cell metabolism, linking PHF2 to lipid droplet–mitochondria contacts and regeneration.

    Evidence Mouse regeneration model, CRISPR KO, phospho-mimetic rescue, live-cell organelle-contact imaging (preprint)

    PMID:bio_10.1101_2025.01.18.630727

    Open questions at the time
    • Preprint not yet peer-reviewed
    • Whether organelle-contact role is chromatin-dependent unresolved
  17. 2026 Medium

    Showed tissue-specific physiological consequences of PHF2 demethylase activity in fast-twitch muscle function in vivo.

    Evidence Skeletal muscle-specific KO mice, ChIP-seq, grip strength, fiber-type phenotyping

    PMID:42006298

    Open questions at the time
    • Single-lab study
    • Fiber-type specificity mechanism not explained
  18. 2025 Medium

    Implicated PHF2 in neuroinflammatory transcriptional control in Alzheimer's models, broadening its disease relevance.

    Evidence ChIP-seq, bidirectional Phf2 manipulation in 5xFAD mice, electrophysiology, behavior, histology

    PMID:40849543

    Open questions at the time
    • Single-lab study
    • Direct vs indirect regulation of inflammatory genes not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PHF2's distinct activities — H3K9me2 demethylation, SREBP1c E3 ligase activity, and demethylase-independent cohesin/heterochromatin structural roles — are coordinated within a single protein, and how upstream phosphorylation and palmitoylation switch between them, remains unresolved.
  • No unified model integrating catalytic, ligase, and structural functions
  • Switch between activating and repressive chromatin modes undefined
  • E3 ligase catalytic mechanism unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 3 GO:0140110 transcription regulator activity 3 GO:0042393 histone binding 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0140104 molecular carrier activity 2 GO:0016740 transferase activity 1 GO:0016874 ligase activity 1
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005730 nucleolus 2
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-1266738 Developmental Biology 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1430728 Metabolism 2 R-HSA-69306 DNA Replication 2 R-HSA-73894 DNA Repair 2
Partners
AMPKARID5BCEBPACEBPDRAD21SUV39H1TP53ZDHHC23
Complex memberships
cohesin

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 PHF2 is enzymatically inactive as a H3K9me2 demethylase by itself but is activated by PKA-mediated phosphorylation; phosphorylated PHF2 then associates with the DNA-binding protein ARID5B, induces demethylation of methylated ARID5B, and the resulting complex targets gene promoters to remove repressive H3K9Me2 marks. Biochemical assays, co-immunoprecipitation, in vitro phosphorylation, ChIP, and cell-based demethylase activity assays Nature cell biology High 21532585
2010 The PHD finger of PHF2 recognizes histone H3K4 trimethylation, and this interaction is essential for PHF2 occupancy and H3K9 demethylation at rDNA promoters, demonstrating cross-talk between H3K4me3 reading and H3K9 demethylase activity. Biochemical binding assays, X-ray crystallography, and ChIP The Journal of biological chemistry High 20129925
2010 The PHF2 Jumonji domain coordinates Fe2+ or Ni2+ via H249, D251, N-oxalylglycine (α-ketoglutarate analog), Y321, and one water molecule in an octahedral arrangement; a Y321H mutation (replacing the atypical tyrosine fifth ligand with histidine) does not restore demethylase activity on histone peptides in vitro, indicating additional regulatory factors are required for enzymatic activity. X-ray crystallography (crystal structures in absence and presence of metal ions), in vitro demethylase activity assay, site-directed mutagenesis (Y321H), metal binding affinity measurement Journal of molecular biology High 21167174
2013 ARID5B physically associates with Sox9 and recruits PHF2 to Sox9 target gene promoters, stimulating H3K9me2 demethylation; loss of Arid5b in mice and cells increases H3K9me2 at chondrogenic gene promoters and impairs chondrogenesis, and PHF2 knockdown inhibits Sox9-induced chondrocyte differentiation. Co-immunoprecipitation, ChIP, mouse knockout model (Arid5b−/−), siRNA knockdown, differentiation assays Nature communications High 24276541
2014 PHF2 physically associates with p53 and promotes p53-driven transcription of downstream targets (e.g., p21) by demethylating the repressive H3K9me2 mark at target promoters; PHF2 depletion abolishes p21 induction by oxaliplatin/doxorubicin despite strong p53 induction in xenograft models. Co-immunoprecipitation, ChIP, siRNA knockdown, xenograft tumor model, Western blotting Oncogene High 25043306
2014 PHF2 inhibits rDNA transcription by competing with the activating demethylase PHF8 for binding to rDNA promoters (through H3K4me2/3 recognition via its PHD) and by recruiting the H3K9me2/3 methyltransferase SUV39H1; demethylase activity of PHF2 is not required for this repressive function. RNAi knockdown, overexpression, ChIP, RNA polymerase I transcription assays, co-immunoprecipitation The Journal of biological chemistry High 25204660
2014 PHF2 physically interacts with the adipogenic transcription factors C/EBPα and C/EBPδ, binds their target gene promoters, and demethylates H3K9me2 there to activate adipogenic gene expression; PHF2 knockdown reduces lipid accumulation and metabolic gene expression during adipocyte differentiation. Co-immunoprecipitation, ChIP, stable shRNA knockdown in 3T3-L1 cells, cDNA microarray, qRT-PCR, Western blotting Molecules and cells Medium 25266703
2018 PHF2 functions as a transcriptional co-activator of ChREBP by erasing H3K9me2 marks at ChREBP-regulated gene promoters in hepatocytes, facilitating lipogenesis; PHF2 also activates Nrf2 target genes, redirecting glucose toward the pentose phosphate pathway and protecting from oxidative stress in diet-induced obesity. ChIP, mouse genetic models, siRNA knockdown, metabolic flux analyses, lipidomics Nature communications High 29844386
2018 PHF2 binds the p53 promoter, demethylates H3K9me2 in that region, and thereby regulates p53 expression; during megakaryocytic and erythroid differentiation, PHF2 downregulation parallels p53 downregulation and knockdown of PHF2 promotes differentiation. ChIP, co-immunoprecipitation, siRNA knockdown, Western blotting, differentiation assays in K562 and CD34+ cells Journal of cellular physiology Medium 29336484
2019 PHF2 controls expression of DNA replication and cell cycle progression genes in neural progenitors by maintaining low H3K9me3 levels at their promoters; PHF2 depletion causes R-loop accumulation, DNA damage, and cell cycle arrest, revealing PHF2 as a guardian of genome stability in neural development. siRNA knockdown in neural progenitors, genome-wide ChIP-seq, R-loop detection (S9.6 immunostaining), DNA damage assays (γH2AX), cell cycle analysis, in vivo chicken spinal cord electroporation Proceedings of the National Academy of Sciences of the United States of America High 31488723
2019 PHF2 promotes long-term memory consolidation by epigenetically reinforcing the TrkB-CREB signaling pathway; PHF2 knockdown in mouse hippocampus impairs memory formation while PHF2 transgenic overexpression enhances it, and PHF2 elevates field EPSP and NMDA receptor-mediated EPSC in CA1 neurons. Lentiviral shRNA knockdown in hippocampus, transgenic overexpression, behavioral tests (fear conditioning), electrophysiology (LTP recordings), ChIP EMBO reports High 31359606
2020 PHF2 promotes DNA repair by homologous recombination by controlling CtIP-dependent resection of DNA double-strand breaks; PHF2 knockdown decreases CtIP and BRCA1 protein and mRNA levels (dependent on PHF2 demethylase activity), impairs BRCA1 and RPA focus formation, delays 53BP1 foci resolution, and reduces Rad51 focus formation and HDR efficiency. siRNA knockdown, immunofluorescence (IRIF foci), HR reporter assay, RPA phosphorylation assays, qRT-PCR, Western blotting, sensitivity assays (PARPi) Nucleic acids research High 32232336
2022 The PHF2 PHD and Jumonji domains together form a complete methyl-lysine binding aromatic cage at their interface: H3K4me3 (and VRK1 K4me3) peptides bind across both domains with affinities (KD ~160 nM for H3, ~42 nM for VRK1) 4–21× higher than for the isolated PHD alone; crystal structures show R2 of the peptide engaging acidic residues on both domains and K4me3 encircled by aromatic residues from both domains. X-ray crystallography, fluorescence polarization binding assays, peptide binding studies The Journal of biological chemistry High 36596360
2023 PHF2 functions as an E3 ubiquitin ligase that directly ubiquitinates and destabilizes SREBP1c, thereby suppressing SREBP1c-dependent lipogenesis in hepatocellular carcinoma; the palmitoyltransferase ZDHHC23 palmitoylates PHF2, enhancing its ubiquitin-dependent proteasomal degradation, which relieves SREBP1c suppression and promotes lipid reprogramming. Co-immunoprecipitation, ubiquitination assays, palmitoylation assays, protein stability assays, siRNA knockdown, overexpression in HepG2 and Hep3B cells Nature communications High 37828054
2023 AMPKα2 directly phosphorylates PHF2 at Ser655, enhancing PHF2 demethylase activity toward H3K9me2 and promoting transcription of epithelial genes (e.g., CDH1); a phospho-mimetic PHF2-S655E mutant reduces H3K9me2 and suppresses lung cancer metastasis, while S655A mutant reverses the anti-metastatic effect of metformin. In vitro kinase assay, co-immunoprecipitation (PHF2–AMPKα2), site-directed mutagenesis (S655E and S655A), H3K9me2 ChIP, loss-of-function (PHF2 KO), cell migration/invasion assays, mouse metastasis model Signal transduction and targeted therapy High 36872368
2024 PHF2 associates with RAD21, a core cohesin subunit, to regulate DNA replication in mouse neural stem cells; PHF2/RAD21 co-bound genomic regions resemble active replication origins; PHF2 loss weakens TAD boundaries and chromatin loops at co-bound loci due to reduced RAD21 occupancy and activates dormant replication origins; notably, PHF2's histone demethylase activity is dispensable for this function. Co-immunoprecipitation, ChIP-seq, Hi-C (genome topology), DNA replication origin mapping, CRISPR/Cas9 PHF2 KO in mouse NSC, catalytic-dead mutant rescue Nucleic acids research High 38808662
2024 PHF2 interacts with heterochromatin components and localizes to pericentromeric heterochromatin (PcH) boundaries where it maintains transcriptional activity essential for silencing satellite repeats; PHF2 depletion increases heterochromatic repeat transcription, decreases H3K9me3 levels, and disrupts PcH organization, causing DNA damage; both the PHD and catalytic Jumonji domains are required for PcH stability. Mass spectrometry (Co-IP interactome), ChIP-seq, RNA-seq, immunofluorescence, CRISPR/Cas9 KO, domain-deletion mutants EMBO reports High 38890452
2024 PHF2 binds to promoter regions of sarcomeric genes (e.g., Mybpc2, Mef2c, Myh7) and demethylates H3K9me2 there; PHF2 KO in C2C12 myoblasts by CRISPR/Cas9 severely reduces sarcomeric gene expression and increases H3K9me2 at those loci during differentiation. CRISPR/Cas9 knockout, RNA-seq, ChIP (H3K9me2), qRT-PCR, Western blotting, differentiation assays PloS one Medium 38701072
2025 Cohesin translocates PHF2 through the genome via DNA loop extrusion; PHF2 binds H3K4me3 nucleosomes at active TSSs and also co-localizes with cohesin; cohesin depletion reduces PHF2 binding at sites lacking H3K4me3; conversely, PHF2 depletion reduces cohesin binding at TSSs lacking CTCF and decreases short cohesin loops while increasing heterochromatic B compartment size. ChIP-seq, co-immunoprecipitation, conditional cohesin depletion (auxin-inducible degron), Wapl/CTCF depletion, Hi-C The EMBO journal High 39748119
2025 PHF2 promotes lipid droplet homeostasis in muscle stem cells (MuSCs) during regenerative myogenesis by facilitating contacts between lipid droplets and mitochondria; PHF2 loss causes lipid droplet accumulation, mitochondrial dysfunction, and impaired regeneration; expression of an AMPKα2-phospho-mimetic PHF2 mutant rescues the phenotype, placing PHF2 downstream of AMPKα2 in this pathway. Mouse muscle regeneration model, CRISPR/Cas9 PHF2 KO, phospho-mimetic mutant rescue, live-cell imaging of lipid droplet–mitochondria contacts, functional regeneration assays bioRxivpreprint Medium bio_10.1101_2025.01.18.630727
2026 PHF2 binds to TSS-downstream regions of Mef2c and other muscle-function genes in fast-twitch muscle fibers and demethylates H3K9me2 there; skeletal muscle-specific PHF2 knockout mice show significantly reduced grip strength with preferential effects in fast-twitch muscles. Skeletal muscle-specific Phf2 KO mice, ChIP-seq, grip strength measurements, fiber-type-specific phenotyping iScience Medium 42006298
2025 PHF2 (KDM7C) regulates inflammatory gene expression in Alzheimer's disease contexts: ChIP-seq combined with bidirectional Phf2 manipulation shows PHF2 controls Stat3, Nfkbia, Nfkb2, Tnfrsf1a, and other neuroinflammation genes; Phf2 knockdown in 5xFAD mice reduces microglial/astrocyte activation and restores glutamatergic synaptic function. ChIP-seq, siRNA knockdown in 5xFAD mice, qRT-PCR, immunohistochemistry, electrophysiology, behavioral testing (Barnes maze) Molecular psychiatry Medium 40849543

Source papers

Stage 0 corpus · 34 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5B. Nature cell biology 154 21532585
2010 Recognition of histone H3K4 trimethylation by the plant homeodomain of PHF2 modulates histone demethylation. The Journal of biological chemistry 126 20129925
2018 The histone demethylase Phf2 acts as a molecular checkpoint to prevent NAFLD progression during obesity. Nature communications 81 29844386
2013 Arid5b facilitates chondrogenesis by recruiting the histone demethylase Phf2 to Sox9-regulated genes. Nature communications 80 24276541
2023 Palmitoylation-driven PHF2 ubiquitination remodels lipid metabolism through the SREBP1c axis in hepatocellular carcinoma. Nature communications 67 37828054
2008 Alterations in candidate genes PHF2, FANCC, PTCH1 and XPA at chromosomal 9q22.3 region: pathological significance in early- and late-onset breast carcinoma. Molecular cancer 66 18990233
2014 PHF2 histone demethylase acts as a tumor suppressor in association with p53 in cancer. Oncogene 64 25043306
2023 Phosphorylation of PHF2 by AMPK releases the repressive H3K9me2 and inhibits cancer metastasis. Signal transduction and targeted therapy 54 36872368
2019 PHF2 histone demethylase prevents DNA damage and genome instability by controlling cell cycle progression of neural progenitors. Proceedings of the National Academy of Sciences of the United States of America 51 31488723
2010 Structural basis for human PHF2 Jumonji domain interaction with metal ions. Journal of molecular biology 42 21167174
2014 The histone demethylase PHF2 promotes fat cell differentiation as an epigenetic activator of both C/EBPα and C/EBPδ. Molecules and cells 39 25266703
2019 MiR-221 Promotes Hepatocellular Carcinoma Cells Migration via Targeting PHF2. BioMed research international 33 31214616
1999 PHF2, a novel PHD finger gene located on human chromosome 9q22. Mammalian genome : official journal of the International Mammalian Genome Society 30 10051327
2021 FOXA2-Interacting FOXP2 Prevents Epithelial-Mesenchymal Transition of Breast Cancer Cells by Stimulating E-Cadherin and PHF2 Transcription. Frontiers in oncology 28 33718155
2020 PHF2 regulates homology-directed DNA repair by controlling the resection of DNA double strand breaks. Nucleic acids research 28 32232336
2019 Histone demethylase PHF2 activates CREB and promotes memory consolidation. EMBO reports 27 31359606
2014 PHD finger protein 2 (PHF2) represses ribosomal RNA gene transcription by antagonizing PHF finger protein 8 (PHF8) and recruiting methyltransferase SUV39H1. The Journal of biological chemistry 20 25204660
2022 HIF-1α-mediated augmentation of miRNA-18b-5p facilitates proliferation and metastasis in osteosarcoma through attenuation PHF2. Scientific reports 17 35729160
2016 Histone Demethylase Gene PHF2 Is Mutated in Gastric and Colorectal Cancers. Pathology oncology research : POR 12 27744626
2018 Epigenetic regulation of megakaryocytic and erythroid differentiation by PHF2 histone demethylase. Journal of cellular physiology 10 29336484
2017 Implication of PHF2 Expression in Clear Cell Renal Cell Carcinoma. Journal of pathology and translational medicine 10 28607325
2020 KDM5A and PHF2 positively control expression of pro-metastatic genes repressed by EWS/Fli1, and promote growth and metastatic properties in Ewing sarcoma. Oncotarget 9 33196691
2025 Cohesin positions the epigenetic reader Phf2 within the genome. The EMBO journal 8 39748119
2024 PHF2 regulates genome topology and DNA replication in neural stem cells via cohesin. Nucleic acids research 8 38808662
2024 PHF2 regulates sarcomeric gene transcription in myogenesis. PloS one 5 38701072
2022 A complete methyl-lysine binding aromatic cage constructed by two domains of PHF2. The Journal of biological chemistry 5 36596360
2018 The expression and biological function of the PHF2 gene in breast cancer. RSC advances 4 35558021
2015 Sequence analysis and minimal replicon determination of a new haloarchaeal plasmid pHF2 isolated from Haloferax sp. strain Q22. Plasmid 4 26601892
2025 Comprehensive understanding of context-specific functions of PHF2 in lipid metabolic tissues. Scientific reports 3 40097484
2024 PHF2-mediated H3K9me balance orchestrates heterochromatin stability and neural progenitor proliferation. EMBO reports 3 38890452
2022 Circ_MBNL3 Restrains Hepatocellular Carcinoma Progression by Sponging miR-873-5p to Release PHF2. Biochemical genetics 3 36380035
2025 Histone demethylase PHF2 regulates inflammatory genes in Alzheimer's disease. Molecular psychiatry 1 40849543
2026 The role of histone demethylase PHF2 as a tumour suppressor in hepatocellular carcinoma by regulating SRXN1. Oncogenesis 0 41554700
2026 PHF2 regulates grip strength via demethylation at the promoter region of the Mef2c. iScience 0 42006298

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