{"gene":"HMGN2","run_date":"2026-04-28T18:06:53","timeline":{"discoveries":[{"year":1999,"finding":"PCAF acetyltransferase specifically acetylates HMGN2 (HMG-17) at lysine 2, and this acetylation reduces the affinity of HMGN2 for nucleosome cores; conversely, nucleosome-bound HMGN2 inhibits PCAF-mediated acetylation of histone H3.","method":"In vitro acetyltransferase assay, mass spectrometry sequence analysis, equilibrium dialysis, competition studies with deletion mutants","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1 — in vitro reconstitution with mutagenesis and mass spectrometry, multiple orthogonal methods in single study","pmids":["10207070"],"is_preprint":false},{"year":1995,"finding":"HMGN2 (HMG-17) acts as a chromatin-specific transcriptional coactivator that increases the efficiency of RNA polymerase II transcription initiation (7- to 40-fold stimulation) only from nucleosomal chromatin templates assembled with the protein, not from protein-free DNA or post-assembly added protein.","method":"In vitro chromatin assembly and transcription assay with regularly spaced nucleosomal arrays, GAL4-VP16 activator, structural analysis","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 1 — reconstituted chromatin transcription system with rigorous controls distinguishing initiation vs. elongation","pmids":["7649479"],"is_preprint":false},{"year":1993,"finding":"HMGN2 (HMG-17) is incorporated into nascent chromatin during replication in a cell-free Xenopus egg system, stabilizes nucleosomal core structure, improves nucleosomal periodicity, and significantly increases transcriptional potential only when incorporated during (not after) chromatin assembly.","method":"Cell-free Xenopus egg extract chromatin assembly, transcription assays with 5S RNA gene and satellite I chromatin, kinetic studies","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 — cell-free reconstitution with kinetic controls, multiple templates","pmids":["8404854"],"is_preprint":false},{"year":1998,"finding":"HMGN2 (HMG-17) stimulates replication efficiency of chromatin templates (SV40 minichromosomes) only when incorporated during chromatin assembly, not post-assembly, and only from chromatin templates, not protein-free DNA; the effect is associated with induction of extended chromatin structure.","method":"In vitro SV40 replication system, minichromosome assembly in Xenopus egg extracts, structural analysis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 — in vitro reconstitution with rigorous controls for timing of incorporation","pmids":["9545265"],"is_preprint":false},{"year":1994,"finding":"Hydroxyl radical footprinting mapped HMGN2 (HMG-17) binding sites on nucleosome cores: two molecules bind per nucleosome, protecting DNA ~25 bp from the end of the core and near the nucleosomal dyad axis, bridging two adjacent DNA strands on the surface, with binding sites overlapping those of linker histones near the dyad.","method":"Hydroxyl radical footprinting of nucleosome cores and H1/H5-depleted chromatosomes","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 — direct structural footprinting assay with defined controls","pmids":["8107104"],"is_preprint":false},{"year":1992,"finding":"The nucleosome-binding domain of HMGN2 (HMG-17) — a 30 amino acid peptide — functions as an independent module: it specifically shifts nucleosome core mobility, elevates thermal denaturation of cores, protects the same DNase I sites as intact protein, and requires histone tails for binding.","method":"Mobility shift assays, thermal denaturation, DNase I digestion, trypsin digestion of histone tails with synthetic peptides and recombinant protein","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 — multiple orthogonal in vitro assays with domain-mapping peptides","pmids":["1453455"],"is_preprint":false},{"year":1998,"finding":"HMGN2 (HMG-17) is released from chromatin during mitosis (metaphase/anaphase), then re-imported into the nucleus in late telophase via active nuclear import requiring energy and importin alpha; the protein contains an intrinsic bipartite nuclear localization signal.","method":"Immunofluorescence colocalization through cell cycle, reconstituted nuclei and permeabilized cell import assays, energy depletion experiments","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 — direct localization experiments with functional import assays and mechanistic dissection","pmids":["9852141"],"is_preprint":false},{"year":1998,"finding":"HMGN2 (HMG-17) colocalizes with sites of active RNA polymerase II transcription; a peptide corresponding to the nucleosomal binding domain of HMG-14/17 displaces HMGN2 from chromatin and arrests pol II transcription; upon transcriptional inhibition, HMGN2 redistributes from chromatin to interchromatin granule clusters (SC35-positive).","method":"Immunofluorescence in tissue culture cells, peptide microinjection into permeabilized cells, alpha-amanitin and actinomycin D treatment","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 — direct localization coupled to functional perturbation, multiple inhibitors tested","pmids":["9843505"],"is_preprint":false},{"year":2007,"finding":"HMGN2 (HMG-17) physically interacts with the PITX2 homeodomain protein to inhibit its DNA-binding activity; beta-catenin forms a ternary PITX2/HMGN2/beta-catenin complex that switches HMGN2 from a transcriptional repressor to an activator; HMG-17 homozygous knockout mice show early embryonic lethality.","method":"Co-immunoprecipitation, EMSA, reporter assays, pull-down, confocal microscopy, homozygous knockout mouse model","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 — reciprocal co-IP, functional EMSA, in vivo knockout, multiple methods","pmids":["18045789"],"is_preprint":false},{"year":2011,"finding":"HMGN2 inducibly binds a novel transactivation domain in nuclear prolactin receptor (PRLr) in a phosphorylation-dependent manner; the HMGN2-PRLr interaction enables Stat5a-responsive promoter binding and transcriptional activation, promoting anchorage-independent growth.","method":"Co-immunoprecipitation, ChIP assays, reporter assays, soft agar anchorage-independent growth assay","journal":"Molecular endocrinology","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP with functional ChIP and cell biology readout","pmids":["21816901"],"is_preprint":false},{"year":2016,"finding":"HDAC6 deacetylates HMGN2 at lysine K2; deacetylation of HMGN2 promotes Stat5a-mediated transcription and breast cancer growth; HDAC6 inhibition increases HMGN2 acetylation and reduces Stat5a signaling in vitro and in vivo.","method":"HDAC6 inhibitor treatment in vitro and in vivo, acetylation Western blot, Stat5a target gene expression, breast cancer growth assays","journal":"Molecular cancer research","confidence":"High","confidence_rationale":"Tier 2 — writer/eraser identified with in vitro and in vivo functional consequence, replicated with pharmacological and genetic approaches","pmids":["27358110"],"is_preprint":false},{"year":2016,"finding":"HMGN2 promotes STAT5 accessibility at prolactin-responsive promoter DNA by facilitating dissociation of linker histone H1; H1 knockdown rescues decreases in PRL-induced transcription caused by HMGN2 knockdown, demonstrating that HMGN2 acts antagonistically to H1 to enable STAT5 chromatin recruitment.","method":"siRNA knockdown of HMGN2 and H1, ChIP for STAT5 and H1, gene expression analysis, cell proliferation assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — epistasis by double knockdown with rescue, ChIP-based chromatin occupancy measurements","pmids":["28035005"],"is_preprint":false},{"year":2014,"finding":"HMGN2 is SUMOylated at lysines K17 and K35 (within the nucleosome-binding domain) by SUMO E3 ligase PIAS1; SENP1 deSUMOylates HMGN2; SUMOylation decreases HMGN2 binding affinity to nucleosome core particles.","method":"In vitro SUMOylation assay, identification of SUMOylated residues by mutagenesis, SUMO1-conjugated HMGN2 reconstituted in E. coli, nucleosome binding assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 — reconstituted SUMOylation system with in vitro nucleosome binding assay, writer/eraser identified with site mutagenesis","pmids":["24872413"],"is_preprint":false},{"year":2009,"finding":"HMGN2 is a component of the global genome repair subpathway of nucleotide excision repair (NER): DT40 cells lacking HMGN2 are hypersensitive to UV irradiation, show increased G2-M checkpoint arrest and apoptosis, and have slower removal of UV-induced DNA lesions from native chromatin, though nucleotide excision repair per se (measured by host cell reactivation) remains intact.","method":"Gene knockout in DT40 cells, UV sensitivity assays, apoptosis and cell cycle analysis, host cell reactivation assay, DNA lesion removal kinetics","journal":"The FEBS journal","confidence":"High","confidence_rationale":"Tier 2 — clean KO with defined cellular phenotype and mechanistic dissection separating global genome repair from NER per se","pmids":["19843163"],"is_preprint":false},{"year":2019,"finding":"Loss of HMGN2 in pluripotent embryonal carcinoma cells leads to global reduction in H3K9 acetylation and disrupts H3K4me3, H3K9ac, H3K27ac, and H3K122ac at Nanog and Oct4 loci, causing loss of pluripotency markers and increased spontaneous neuronal differentiation.","method":"HMGN2 knockout cell lines, ChIP-seq for histone marks, gene expression analysis, differentiation marker assays","journal":"Epigenetics & chromatin","confidence":"High","confidence_rationale":"Tier 2 — KO with ChIP-seq profiling of multiple histone modifications, defined cellular phenotype","pmids":["31831052"],"is_preprint":false},{"year":2021,"finding":"Lysine succinylation at K30 within the HMGN2 nucleosome-binding domain (installed via a succinyl lysine analogue) significantly decreases HMGN2 binding to mononucleosomes and promotes nucleosomal DNA unwrapping at entry/exit regions, increasing DNA accessibility.","method":"Site-specific incorporation of succinyl lysine analogue, mononucleosome binding assays, nucleosomal DNA accessibility assays","journal":"RSC chemical biology","confidence":"High","confidence_rationale":"Tier 1 — site-specific PTM mimetic reconstituted in vitro with nucleosome binding and DNA accessibility assays","pmids":["34458839"],"is_preprint":false},{"year":2013,"finding":"Binding of HMGN2 to reconstituted nucleosomes increases the winding angle of nucleosomal DNA (measured by circular dichroism), with the extent of structural change differing from that of HMGN1, suggesting distinct abilities to facilitate nucleosome remodeling.","method":"CD spectroscopy of nucleosomes reconstituted from unmodified recombinant histones and synthetic positioning DNA, with purified HMGN1 and HMGN2","journal":"FEBS open bio","confidence":"Medium","confidence_rationale":"Tier 1 — in vitro reconstitution with spectroscopic readout, single lab, single method","pmids":["23772392"],"is_preprint":false},{"year":2011,"finding":"HMGN2 promotes LPS-induced beta-defensin-2 expression in A549 cells by prolonging nuclear retention of NF-κB p65, enhancing p65 acetylation, increasing histone acetyltransferase activity, and promoting p65-Ser536 phosphorylation; ChIP shows HMGN2 and p65 synergistically bind the HBD-2 promoter.","method":"siRNA knockdown, ChIP, Western blot for p65 nuclear retention and phosphorylation, HAT activity assay, reporter assay","journal":"The FEBS journal","confidence":"Medium","confidence_rationale":"Tier 2 — ChIP and multiple signaling readouts, single lab","pmids":["21518253"],"is_preprint":false},{"year":2022,"finding":"HMGN2 interacts with transcription factor Lef-1 through its HMG-box domain and with Dlx2, FoxJ1, and Pitx2; HMGN2 binding to Lef-1 inhibits Lef-1 DNA-binding activity; HMGN2 associates with H4K5ac and H3K4me2 marks at the Dlx2 promoter; miR-23a/b directly target Hmgn2 to post-transcriptionally suppress its expression; Hmgn2 ablation in mice increases amelogenin expression due to increased transcriptional activity of Pitx2, Dlx2, Lef-1, and FoxJ1.","method":"Bimolecular fluorescence complementation, pull-down, co-immunoprecipitation, EMSA, ChIP, mouse knockout, in situ hybridization, luciferase reporter assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal methods including EMSA, ChIP, Co-IP, in vivo knockout with defined phenotype","pmids":["35872015"],"is_preprint":false},{"year":2025,"finding":"HMGN1 and HMGN2 preferentially bind nucleosomes with acetylated H3 tail residues and H2A.Z-containing nucleosomes; HMGN1/HMGN2 binding to nucleosomes reduces p300-mediated acetylation of H3K18, H3K23, and H3K27; Hmgn1/Hmgn2 double-knockout mESCs show increased H3K27me2/me3 and altered expression of ~1000 genes.","method":"Nucleosome binding assays, in vitro p300 acetylation assays, epiproteomic mass spectrometry, RNA-seq in CRISPR-engineered knockout mESCs","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 — in vitro reconstitution with PTM-modified nucleosomes, acetylation assay with p300, epiproteomic MS in KO cells","pmids":["41325801"],"is_preprint":false},{"year":1987,"finding":"HMGN2 (HMG17) is present only downstream of transcription start sites in active chromatin of vitellogenin II, lysozyme, and ovalbumin genes, as demonstrated by immunofractionation of oligonucleosomes with monoclonal antibodies and analysis by two independent experimental approaches.","method":"Monoclonal antibody immunoisolation of oligonucleosomes, gene-specific DNA probe analysis of active chromatin from chicken liver and oviduct","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 — two independent experimental approaches with gene-specific resolution","pmids":["3665881"],"is_preprint":false},{"year":1984,"finding":"HMG17 (HMGN2) greatly facilitates catenation of double-stranded DNA rings by DNA topoisomerases types I and II, promoting formation of large catenated networks even at low DNA concentrations where catenanes are otherwise absent.","method":"In vitro topoisomerase catenation assay, gel electrophoresis, electron microscopy, restriction enzyme cleavage","journal":"Archives of biochemistry and biophysics","confidence":"Medium","confidence_rationale":"Tier 1 — in vitro reconstitution with multiple topoisomerases, single lab","pmids":["6326673"],"is_preprint":false},{"year":1997,"finding":"HMGN2 (HMG-17) nucleosomes are organized in clusters of ~6 contiguous HMG-17-containing nucleosomes in cellular chromatin, and nucleosomes containing HMG-17 are devoid of HMG-14 (the two segregate into distinct nuclear domains), as shown by immunofractionation and confocal immunofluorescence.","method":"Confocal immunofluorescence microscopy, immunofractionation with affinity-purified antibodies, quantitative analysis","journal":"Journal of molecular biology","confidence":"Medium","confidence_rationale":"Tier 2 — direct imaging and biochemical fractionation, single lab","pmids":["9417927"],"is_preprint":false},{"year":2002,"finding":"Butyrate-induced hyperacetylation of HMGN2 alters its binding properties to chromatin in HT29 colon adenocarcinoma cells: acetylated HMGN2 is solubilized from chromatin, as demonstrated by FRAP of HMG-N2-EGFP fusion proteins and solubilization of endogenous acetylated HMGN2 in permeabilized cells.","method":"Butyrate treatment, transfected EGFP fusion protein dynamics, solubilization of acetylated HMGN2 from permeabilized cells, Northern and Western blot","journal":"International journal of cancer","confidence":"Medium","confidence_rationale":"Tier 2-3 — live cell imaging with EGFP fusion and biochemical fractionation, single lab","pmids":["11807779"],"is_preprint":false},{"year":2024,"finding":"HMGN2 binds to histones and promotes stability of H3K27ac at the CDC20 promoter region, enhancing CDC20 transcriptional activity and accelerating glioma cell proliferation; HMGN2 knockout reduces CDC20 expression and cell cycle progression.","method":"ChIP for H3K27ac at CDC20 promoter, HMGN2 knockdown/knockout, gene expression and cell proliferation assays","journal":"Genes & diseases","confidence":"Medium","confidence_rationale":"Tier 2 — ChIP with functional KO, single lab","pmids":["40092489"],"is_preprint":false},{"year":2025,"finding":"SUMOylated HMGN2 (via PIAS1) enhances interaction with transcription factor PAX5, inhibiting PAX5 activity and driving macrophage M1 polarization; PIAS1 knockdown reduces HMGN2 SUMOylation, restoring PAX5-mediated M2 polarization and suppressing NF-κB inflammatory signaling in atherosclerosis.","method":"Co-immunoprecipitation, PIAS1 knockdown, foam macrophage model, ApoE-/- mouse model, ELISA, Western blot, immunofluorescence","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2-3 — Co-IP with in vivo model, single lab, functional readout through macrophage polarization","pmids":["40834970"],"is_preprint":false},{"year":2005,"finding":"HMGN2 exhibits antimicrobial activity against Gram-negative bacteria and Candida; the alpha-helical domain (residues 18-48) is essential and sufficient for antimicrobial activity, while N-terminal and C-terminal fragments are inactive.","method":"In vitro antimicrobial assays (MIC, MBC) with recombinant full-length and domain fragments, synthetic peptides","journal":"Acta pharmacologica Sinica","confidence":"Medium","confidence_rationale":"Tier 1 — in vitro domain mapping with recombinant and synthetic peptides, single lab","pmids":["16115376"],"is_preprint":false},{"year":2017,"finding":"HMGN2 facilitates Nrf2 nuclear translocation upon pyocyanin stimulation in A549 cells, elevating antioxidant gene expression and reducing ROS; HMGN2 also regulates actin cytoskeleton rearrangement to attenuate Pseudomonas aeruginosa internalization via ROS elimination.","method":"HMGN2 knockdown/overexpression, ROS measurement, Nrf2 nuclear fractionation, actin staining, bacterial invasion assays","journal":"Free radical biology & medicine","confidence":"Medium","confidence_rationale":"Tier 2 — loss- and gain-of-function with multiple mechanistic readouts, single lab","pmids":["28408162"],"is_preprint":false},{"year":2019,"finding":"HMGN2 deficiency in macrophages promotes M1 polarization during NTM infection by enhancing activation of NF-κB and MAPK signaling, leading to increased iNOS, IFNγ, TNF-α, IL-1β, IL-6 expression and NO production, which affects NTM survival.","method":"siRNA knockdown, macrophage polarization marker analysis, NF-κB/MAPK signaling assays, intracellular bacterial survival assay","journal":"Journal of cellular and molecular medicine","confidence":"Medium","confidence_rationale":"Tier 2 — loss-of-function with defined signaling pathway readout, single lab","pmids":["31596045"],"is_preprint":false},{"year":2012,"finding":"HMGN2 acts as a positive regulator of LPS-induced mouse beta-defensin-3 and -4 expression in vivo; HMGN2 shRNA interference reduces mBD-3 and mBD-4 but not mBD-1 expression in maternal, embryonic, and neonatal mouse tissues upon LPS stimulation.","method":"shRNA knockdown in vivo in pregnant ICR mice, real-time PCR for defensin and HMGN2 expression across developmental timepoints and tissues","journal":"Inflammation","confidence":"Medium","confidence_rationale":"Tier 2 — in vivo knockdown with gene-specific phenotypic readout, single lab","pmids":["21594618"],"is_preprint":false},{"year":2016,"finding":"HMGN2 knockdown in A549 cells increases α5β1 integrin expression on cell membranes, talin expression, FAK and Src phosphorylation, and actin polymerization, resulting in increased Klebsiella pneumoniae internalization.","method":"siRNA knockdown, cDNA microarray, flow cytometry for integrin surface expression, phospho-Western blot, bacterial invasion assay","journal":"International journal of molecular medicine","confidence":"Medium","confidence_rationale":"Tier 2 — siRNA KD with signaling pathway dissection, single lab","pmids":["27460641"],"is_preprint":false},{"year":2025,"finding":"HMGN2 knockout in RAW264.7 macrophages enhances bactericidal and phagocytic activity by transcriptionally promoting CD14 expression via increased H3K4me3, H3K9ac, and H3K27ac at the CD14 gene promoter, activating CD14-mediated MAPK signaling and NO production.","method":"CRISPR-Cas9 knockout, ChIP for histone marks at CD14 promoter, bacterial killing assays, MAPK signaling analysis","journal":"Frontiers in immunology","confidence":"Medium","confidence_rationale":"Tier 2 — CRISPR KO with ChIP-based mechanistic dissection, single lab","pmids":["41246296"],"is_preprint":false}],"current_model":"HMGN2 is a nucleosome-binding protein that binds to the nucleosomal core (via a 30-aa nucleosome-binding domain requiring histone tails) and acts as a chromatin architectural element: it unfolds higher-order chromatin structure to enhance RNA polymerase II transcription initiation and DNA replication from chromatin templates; its chromatin affinity and activity are modulated by post-translational modifications (acetylation by PCAF at K2, deacetylation by HDAC6, SUMOylation by PIAS1 at K17/K35, and succinylation at K30, all of which reduce nucleosome binding), and it preferentially associates with acetylated H3 and H2A.Z-containing nucleosomes to regulate active chromatin states and suppress repressive H3K27 methylation; HMGN2 also functions as a molecular switch regulating homeodomain and other transcription factor activity through direct protein interactions, modulates NF-κB and Nrf2 signaling in innate immune responses, and exhibits extranuclear antimicrobial activity through its alpha-helical domain."},"narrative":{"teleology":[{"year":1984,"claim":"Early work established that HMGN2 alters DNA topology by facilitating topoisomerase-mediated catenation, indicating a role in modulating DNA structure beyond simple binding.","evidence":"In vitro topoisomerase catenation assay with purified HMG-17","pmids":["6326673"],"confidence":"Medium","gaps":["Single lab, single method","Physiological relevance of catenation-promoting activity unclear","No chromatin context tested"]},{"year":1987,"claim":"Immunofractionation of oligonucleosomes revealed that HMGN2 is selectively enriched downstream of transcription start sites in active genes, establishing its association with transcriptionally active chromatin domains.","evidence":"Monoclonal antibody immunoisolation of oligonucleosomes from chicken liver and oviduct with gene-specific probes","pmids":["3665881"],"confidence":"High","gaps":["Causal relationship between HMGN2 presence and transcription not tested","Mechanism of preferential deposition at active genes unknown"]},{"year":1992,"claim":"Mapping of the nucleosome-binding domain to a 30-amino-acid peptide that autonomously recognizes nucleosome cores and requires histone tails defined the minimal structural module for HMGN2–chromatin interaction.","evidence":"Mobility shift, thermal denaturation, DNase I footprinting, and trypsin digestion with synthetic peptides and recombinant protein","pmids":["1453455"],"confidence":"High","gaps":["Specific histone tail residues required not identified","No structure of the domain–nucleosome complex"]},{"year":1993,"claim":"Cell-free chromatin assembly experiments demonstrated that HMGN2 must be incorporated during replication-coupled assembly to enhance transcription, revealing that it acts as a constitutive chromatin component rather than a post-hoc modifier.","evidence":"Xenopus egg extract chromatin assembly with transcription assays on 5S RNA gene and satellite I templates","pmids":["8404854"],"confidence":"High","gaps":["Mechanism of co-assembly incorporation unknown","Whether replication-independent assembly also suffices not tested"]},{"year":1994,"claim":"Hydroxyl radical footprinting resolved the precise binding geometry: two HMGN2 molecules bind per nucleosome near the dyad and ~25 bp from core DNA ends, overlapping linker histone sites, explaining how HMGN2 and H1 compete for the same nucleosome.","evidence":"Hydroxyl radical footprinting of nucleosome cores and H1/H5-depleted chromatosomes","pmids":["8107104"],"confidence":"High","gaps":["No atomic-resolution structure","How two HMGN2 molecules cooperatively bind is not resolved"]},{"year":1995,"claim":"Reconstituted chromatin transcription assays quantified a 7–40-fold stimulation of RNA polymerase II transcription initiation, establishing HMGN2 as a bona fide chromatin-specific transcriptional coactivator.","evidence":"In vitro transcription from regularly spaced nucleosomal arrays with GAL4-VP16 activator","pmids":["7649479"],"confidence":"High","gaps":["Whether elongation is also affected was not resolved","Generality across diverse promoters not tested"]},{"year":1997,"claim":"Discovery that HMGN2-containing nucleosomes cluster in contiguous runs of ~6 and are mutually exclusive with HMGN1 revealed that HMGN variants define distinct chromatin domains rather than being randomly distributed.","evidence":"Immunofractionation and confocal immunofluorescence microscopy","pmids":["9417927"],"confidence":"Medium","gaps":["Single lab","Mechanism of domain segregation unknown","Functional consequence of clustering not tested"]},{"year":1998,"claim":"Three concurrent studies resolved HMGN2 dynamics and function: it colocalizes with active pol II sites, is released from chromatin during mitosis and re-imported via importin-α in telophase, and stimulates SV40 replication efficiency only from chromatin assembled with the protein.","evidence":"Immunofluorescence through cell cycle, nuclear import assays, peptide microinjection, SV40 minichromosome replication","pmids":["9852141","9843505","9545265"],"confidence":"High","gaps":["Whether mitotic release serves a regulatory function or is passive is unknown","Replication stimulation mechanism at the molecular level unresolved"]},{"year":1999,"claim":"Identification of PCAF as the acetyltransferase that acetylates K2, with acetylation reducing nucleosome affinity, established the first post-translational switch controlling HMGN2–chromatin interaction; reciprocally, nucleosome-bound HMGN2 inhibits PCAF acetylation of H3.","evidence":"In vitro acetyltransferase assay, mass spectrometry, equilibrium dialysis","pmids":["10207070"],"confidence":"High","gaps":["In vivo dynamics of K2 acetylation not characterized","Identity of additional acetyltransferases not excluded"]},{"year":2005,"claim":"Domain mapping revealed that the alpha-helical region (residues 18–48, overlapping the nucleosome-binding domain) has direct antimicrobial activity against Gram-negative bacteria and Candida, indicating an extranuclear function.","evidence":"In vitro MIC/MBC assays with recombinant fragments and synthetic peptides","pmids":["16115376"],"confidence":"Medium","gaps":["Single lab","In vivo antimicrobial relevance not demonstrated","Mechanism of membrane disruption not characterized"]},{"year":2007,"claim":"Discovery that HMGN2 directly inhibits PITX2 DNA binding, with β-catenin converting the complex into a transcriptional activator, and that homozygous HMGN2 knockout mice are embryonic lethal, established HMGN2 as a molecular switch for homeodomain transcription factor activity essential for development.","evidence":"Co-IP, EMSA, reporter assays, confocal microscopy, homozygous knockout mouse","pmids":["18045789"],"confidence":"High","gaps":["Stage and cause of embryonic lethality not defined","Whether all homeodomain interactions share the same mechanism unclear"]},{"year":2009,"claim":"HMGN2 knockout DT40 cells showed impaired removal of UV-induced lesions from chromatin without affecting core NER catalysis, demonstrating that HMGN2 facilitates the global genome repair subpathway through chromatin accessibility rather than repair enzyme function.","evidence":"DT40 gene knockout, UV sensitivity, host cell reactivation, DNA lesion kinetics","pmids":["19843163"],"confidence":"High","gaps":["Mechanism of chromatin opening for NER factors not defined","Mammalian confirmation not provided"]},{"year":2011,"claim":"Two studies connected HMGN2 to innate immune transcriptional regulation: it promotes LPS-induced β-defensin-2 expression by enhancing NF-κB p65 nuclear retention and acetylation, and binds nuclear prolactin receptor in a phosphorylation-dependent manner to enable Stat5a-driven transcription.","evidence":"siRNA knockdown with ChIP, reporter assays, HAT activity measurement; Co-IP and ChIP for Stat5a promoter binding","pmids":["21518253","21816901"],"confidence":"Medium","gaps":["Single labs for each study","Whether HMGN2–p65 interaction is direct or chromatin-mediated unclear","In vivo relevance of PRLr interaction not established"]},{"year":2014,"claim":"Identification of PIAS1-mediated SUMOylation at K17 and K35 within the nucleosome-binding domain, reversed by SENP1, provided a second PTM switch that reduces nucleosome affinity, paralleling acetylation at K2.","evidence":"In vitro SUMOylation with site mutagenesis, reconstituted nucleosome binding assays","pmids":["24872413"],"confidence":"High","gaps":["In vivo SUMOylation dynamics and downstream transcriptional consequences not characterized","Interplay between SUMOylation and acetylation not tested"]},{"year":2016,"claim":"The acetyltransferase/deacetylase cycle at K2 was completed by identifying HDAC6 as the eraser; deacetylation promotes Stat5a transcription and breast cancer growth, linking HMGN2 PTM status to oncogenic signaling. Concurrently, epistasis experiments showed HMGN2 antagonizes linker histone H1 to enable STAT5 chromatin access.","evidence":"HDAC6 inhibitor treatment in vitro/in vivo with Stat5a target gene readouts; double knockdown of HMGN2 and H1 with ChIP","pmids":["27358110","28035005"],"confidence":"High","gaps":["Whether HDAC6-HMGN2 axis operates in non-breast contexts unknown","Structural basis for H1–HMGN2 competition at specific loci not resolved"]},{"year":2019,"claim":"Loss of HMGN2 in embryonal carcinoma cells globally reduced H3K9ac and disrupted active marks at pluripotency loci (Nanog, Oct4), causing spontaneous neuronal differentiation and establishing HMGN2 as a guardian of the active chromatin landscape required for pluripotency.","evidence":"HMGN2 knockout cell lines, ChIP-seq for multiple histone marks, differentiation marker analysis","pmids":["31831052"],"confidence":"High","gaps":["Whether effect is direct binding at pluripotency loci or indirect global chromatin change unresolved","In vivo embryonic stem cell confirmation lacking"]},{"year":2021,"claim":"Site-specific succinylation at K30 in the nucleosome-binding domain was shown to decrease nucleosome binding and promote DNA unwrapping at entry/exit sites, adding a third class of PTM that regulates HMGN2–nucleosome interaction.","evidence":"Succinyl lysine analogue incorporation with mononucleosome binding and DNA accessibility assays","pmids":["34458839"],"confidence":"High","gaps":["Physiological writer/eraser for K30 succinylation not identified","In vivo prevalence of K30 succinylation unknown"]},{"year":2022,"claim":"HMGN2 was shown to interact with and inhibit Lef-1 DNA binding in addition to PITX2, Dlx2, and FoxJ1, with Hmgn2 ablation in mice increasing amelogenin expression; miR-23a/b were identified as post-transcriptional regulators of Hmgn2, broadening the homeodomain switch model and revealing upstream control of HMGN2 levels.","evidence":"BiFC, pull-down, Co-IP, EMSA, ChIP, mouse knockout, luciferase reporters","pmids":["35872015"],"confidence":"High","gaps":["Whether miR-23a/b regulation is tissue-specific not determined","Structural basis for homeodomain recognition by HMGN2 unknown"]},{"year":2025,"claim":"Two studies extended HMGN2 biology: it preferentially binds acetylated-H3 and H2A.Z nucleosomes, limits p300-mediated H3K27 acetylation, and suppresses H3K27me2/me3 (with HMGN1); separately, PIAS1-mediated SUMOylation of HMGN2 enhances its interaction with PAX5 to drive macrophage M1 polarization and NF-κB signaling in atherosclerosis.","evidence":"Reconstituted nucleosome binding with modified histones, p300 acetylation assay, epiproteomic MS in CRISPR KO mESCs; Co-IP with PIAS1 knockdown in ApoE−/− mouse model","pmids":["41325801","40834970"],"confidence":"High","gaps":["How HMGN2 binding to acetylated nucleosomes mechanistically suppresses H3K27me3 not resolved","Whether SUMOylation-dependent PAX5 interaction occurs genome-wide unknown","Relative contributions of HMGN1 vs HMGN2 to H3K27me3 suppression not separated"]},{"year":null,"claim":"No high-resolution structure of HMGN2 bound to a nucleosome exists, the mechanism by which HMGN2 is selectively deposited into active chromatin domains during replication is unknown, and how multiple PTM switches (acetylation, SUMOylation, succinylation) are coordinated in vivo to tune chromatin architecture remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No atomic structure of HMGN2–nucleosome complex","Mechanism of replication-coupled chromatin incorporation unknown","Combinatorial PTM regulation in vivo not addressed","Cause of embryonic lethality in knockout mice not defined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[4,5,15,16,19]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[1,8,11,17,18,25]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1,8,9,11,18,24]}],"localization":[{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[4,5,7,20,22]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[6,7,9]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[4,14,19]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[1,7,8,9,11,14,24]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[2,3,14,15,16,19]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[13]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[17,25,28,29,31]},{"term_id":"R-HSA-69306","term_label":"DNA Replication","supporting_discovery_ids":[2,3]}],"complexes":[],"partners":["PITX2","LEF1","PCAF","HDAC6","PIAS1","PRLR","PAX5","CTNNB1"],"other_free_text":[]},"mechanistic_narrative":"HMGN2 is a nucleosome-binding chromatin architectural protein that modulates higher-order chromatin structure to regulate transcription, replication, and DNA repair. Its 30-amino-acid nucleosome-binding domain contacts two sites per nucleosome core near the dyad axis and entry/exit regions, requiring histone tails for binding and antagonizing linker histone H1 occupancy; incorporation during chromatin assembly unfolds chromatin and enhances RNA polymerase II transcription initiation and DNA replication from nucleosomal templates [PMID:7649479, PMID:9545265, PMID:8107104, PMID:1453455, PMID:28035005]. HMGN2 preferentially associates with acetylated H3 and H2A.Z-containing nucleosomes, maintains active histone marks (H3K27ac, H3K9ac, H3K4me3) at target loci, suppresses H3K27 methylation, and its chromatin binding is negatively regulated by acetylation at K2 (written by PCAF, erased by HDAC6), SUMOylation at K17/K35 (by PIAS1), and succinylation at K30 [PMID:10207070, PMID:41325801, PMID:24872413, PMID:34458839, PMID:27358110]. Beyond its chromatin role, HMGN2 directly interacts with homeodomain transcription factors (PITX2, Lef-1, Dlx2) to inhibit their DNA binding, modulates NF-κB and Nrf2 signaling in innate immune responses, and its alpha-helical domain possesses intrinsic antimicrobial activity against Gram-negative bacteria [PMID:18045789, PMID:35872015, PMID:21518253, PMID:16115376, PMID:31596045]."},"prefetch_data":{"uniprot":{"accession":"P05204","full_name":"Non-histone chromosomal protein HMG-17","aliases":["High mobility group nucleosome-binding domain-containing protein 2"],"length_aa":90,"mass_kda":9.4,"function":"Binds to the inner side of the nucleosomal DNA thus altering the interaction between the DNA and the histone octamer. May be involved in the process which maintains transcribable genes in a unique chromatin conformation (By similarity)","subcellular_location":"Nucleus; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/P05204/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/HMGN2","classification":"Common Essential","n_dependent_lines":511,"n_total_lines":1090,"dependency_fraction":0.4688073394495413},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000198830","cell_line_id":"CID001833","localizations":[{"compartment":"chromatin","grade":3},{"compartment":"nucleoplasm","grade":2}],"interactors":[{"gene":"NAA40","stoichiometry":10.0},{"gene":"H2AFY2","stoichiometry":10.0},{"gene":"ZNF280C","stoichiometry":0.2},{"gene":"MDC1","stoichiometry":0.2},{"gene":"PARVB","stoichiometry":0.2},{"gene":"BAZ1A","stoichiometry":0.2},{"gene":"BAZ1B","stoichiometry":0.2},{"gene":"BARD1","stoichiometry":0.2},{"gene":"MECP2","stoichiometry":0.2},{"gene":"WHSC1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001833","total_profiled":1310},"omim":[{"mim_id":"611314","title":"HIGH MOBILITY GROUP NUCLEOSOMAL BINDING PROTEIN 2 PSEUDOGENE 46; HMGN2P46","url":"https://www.omim.org/entry/611314"},{"mim_id":"604502","title":"HIGH MOBILITY GROUP NUCLEOSOMAL BINDING PROTEIN 3; HMGN3","url":"https://www.omim.org/entry/604502"},{"mim_id":"163920","title":"HIGH MOBILITY GROUP NUCLEOSOMAL BINDING PROTEIN 1; HMGN1","url":"https://www.omim.org/entry/163920"},{"mim_id":"163910","title":"HIGH MOBILITY GROUP NUCLEOSOMAL BINDING PROTEIN 2; HMGN2","url":"https://www.omim.org/entry/163910"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Nucleoli","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/HMGN2"},"hgnc":{"alias_symbol":[],"prev_symbol":["HMG17"]},"alphafold":{"accession":"P05204","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P05204","model_url":"https://alphafold.ebi.ac.uk/files/AF-P05204-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P05204-F1-predicted_aligned_error_v6.png","plddt_mean":67.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=HMGN2","jax_strain_url":"https://www.jax.org/strain/search?query=HMGN2"},"sequence":{"accession":"P05204","fasta_url":"https://rest.uniprot.org/uniprotkb/P05204.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P05204/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P05204"}},"corpus_meta":[{"pmid":"12032302","id":"PMC_12032302","title":"A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo.","date":"2002","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/12032302","citation_count":205,"is_preprint":false},{"pmid":"6460317","id":"PMC_6460317","title":"Autoantibodies to nucleosomal proteins: antibodies to HMG-17 in autoimmune diseases.","date":"1982","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/6460317","citation_count":84,"is_preprint":false},{"pmid":"10207070","id":"PMC_10207070","title":"Specific acetylation of chromosomal protein HMG-17 by PCAF alters its interaction with nucleosomes.","date":"1999","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/10207070","citation_count":80,"is_preprint":false},{"pmid":"3665881","id":"PMC_3665881","title":"Chromatin from transcribed genes contains HMG17 only downstream from the starting point of transcription.","date":"1987","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/3665881","citation_count":73,"is_preprint":false},{"pmid":"7649479","id":"PMC_7649479","title":"HMG17 is a chromatin-specific transcriptional coactivator that increases the efficiency of transcription initiation.","date":"1995","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/7649479","citation_count":69,"is_preprint":false},{"pmid":"1453455","id":"PMC_1453455","title":"Nucleosome core binding region of chromosomal protein HMG-17 acts as an independent functional domain.","date":"1992","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/1453455","citation_count":66,"is_preprint":false},{"pmid":"3754870","id":"PMC_3754870","title":"Chromosomal protein HMG-17. 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Correlation with systemic lupus erythematosus clinical activity and with antibodies to double-stranded DNA.","date":"1993","source":"Arthritis and rheumatism","url":"https://pubmed.ncbi.nlm.nih.gov/8318042","citation_count":12,"is_preprint":false},{"pmid":"9016555","id":"PMC_9016555","title":"Neither HMG-14a nor HMG-17 gene function is required for growth of chicken DT40 cells or maintenance of DNaseI-hypersensitive sites.","date":"1997","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/9016555","citation_count":12,"is_preprint":false},{"pmid":"21518253","id":"PMC_21518253","title":"The chromosomal protein HMGN2 mediates lipopolysaccharide-induced expression of β-defensins in A549 cells.","date":"2011","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/21518253","citation_count":11,"is_preprint":false},{"pmid":"7565703","id":"PMC_7565703","title":"The chicken HMG-17 gene is dispensable for cell growth in vitro.","date":"1995","source":"Molecular 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cytogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/9973936","citation_count":10,"is_preprint":false},{"pmid":"23772392","id":"PMC_23772392","title":"Nucleosome structural changes induced by binding of non-histone chromosomal proteins HMGN1 and HMGN2.","date":"2013","source":"FEBS open bio","url":"https://pubmed.ncbi.nlm.nih.gov/23772392","citation_count":10,"is_preprint":false},{"pmid":"29549670","id":"PMC_29549670","title":"Non-histone nuclear protein HMGN2 differently regulates the urothelium barrier function by altering expression of antimicrobial peptides and tight junction protein genes in UPEC J96-infected bladder epithelial cell monolayer.","date":"2018","source":"Acta biochimica Polonica","url":"https://pubmed.ncbi.nlm.nih.gov/29549670","citation_count":10,"is_preprint":false},{"pmid":"35872015","id":"PMC_35872015","title":"HMGN2 represses gene transcription via interaction with transcription factors Lef-1 and Pitx2 during amelogenesis.","date":"2022","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/35872015","citation_count":9,"is_preprint":false},{"pmid":"29401165","id":"PMC_29401165","title":"HMGN2: An Antitumor Effector Molecule of γδT Cells.","date":"2018","source":"Journal of immunotherapy (Hagerstown, Md. : 1997)","url":"https://pubmed.ncbi.nlm.nih.gov/29401165","citation_count":9,"is_preprint":false},{"pmid":"24031744","id":"PMC_24031744","title":"Expression of HMGB1 and HMGN2 in gingival tissues, GCF and PICF of periodontitis patients and peri-implantitis.","date":"2011","source":"Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]","url":"https://pubmed.ncbi.nlm.nih.gov/24031744","citation_count":9,"is_preprint":false},{"pmid":"8037838","id":"PMC_8037838","title":"Autoantibodies to HMG-17 nucleosomal protein in patients with scleroderma.","date":"1994","source":"Journal of autoimmunity","url":"https://pubmed.ncbi.nlm.nih.gov/8037838","citation_count":9,"is_preprint":false},{"pmid":"33589921","id":"PMC_33589921","title":"Prolactin Drives a Dynamic STAT5A/HDAC6/HMGN2 Cis-Regulatory Landscape Exploitable in ER+ Breast Cancer.","date":"2021","source":"Endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/33589921","citation_count":8,"is_preprint":false},{"pmid":"27460641","id":"PMC_27460641","title":"Knockdown of HMGN2 increases the internalization of Klebsiella pneumoniae by respiratory epithelial cells through the regulation of α5β1 integrin expression.","date":"2016","source":"International journal of molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/27460641","citation_count":8,"is_preprint":false},{"pmid":"16115376","id":"PMC_16115376","title":"Alpha-helical domain is essential for antimicrobial activity of high mobility group nucleosomal binding domain 2 (HMGN2).","date":"2005","source":"Acta pharmacologica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/16115376","citation_count":8,"is_preprint":false},{"pmid":"2317791","id":"PMC_2317791","title":"Expression of chromosomal proteins HMG-14 and HMG-17 in transformed human cells.","date":"1990","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/2317791","citation_count":8,"is_preprint":false},{"pmid":"32152397","id":"PMC_32152397","title":"Human HMGN1 and HMGN2 are not required for transcription-coupled DNA repair.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32152397","citation_count":7,"is_preprint":false},{"pmid":"8512325","id":"PMC_8512325","title":"Isolation by a new method and sequence analysis of chromosomal HMG-17 protein from porcine thymus.","date":"1993","source":"Archives of biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/8512325","citation_count":7,"is_preprint":false},{"pmid":"35861945","id":"PMC_35861945","title":"Recombinant jurkat cells (HMGN2-T cells) secrete cytokines and inhibit the growth of tumor cells.","date":"2022","source":"Journal of molecular histology","url":"https://pubmed.ncbi.nlm.nih.gov/35861945","citation_count":6,"is_preprint":false},{"pmid":"34458839","id":"PMC_34458839","title":"Lysine succinylation on non-histone chromosomal protein HMG-17 (HMGN2) regulates nucleosomal DNA accessibility by disrupting the HMGN2-nucleosome association.","date":"2021","source":"RSC chemical biology","url":"https://pubmed.ncbi.nlm.nih.gov/34458839","citation_count":6,"is_preprint":false},{"pmid":"25022381","id":"PMC_25022381","title":"HMGN2 protein inhibits the growth of infected T24 cells in vitro.","date":"2014","source":"Journal of cancer research and therapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/25022381","citation_count":6,"is_preprint":false},{"pmid":"29216626","id":"PMC_29216626","title":"Evidence For Hmgn2 Involvement in Mouse Embryo Implantation and Decidualization.","date":"2017","source":"Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/29216626","citation_count":5,"is_preprint":false},{"pmid":"6477923","id":"PMC_6477923","title":"Conformation of the HMG17-nucleosome complex.","date":"1984","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/6477923","citation_count":5,"is_preprint":false},{"pmid":"35117527","id":"PMC_35117527","title":"Exogenous HMGN2 inhibits the migration and invasion of osteosarcoma cell lines.","date":"2020","source":"Translational cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/35117527","citation_count":4,"is_preprint":false},{"pmid":"7517709","id":"PMC_7517709","title":"Sera from JRA patients contain antibodies against a defined epitope in chromosomal protein HMG-17.","date":"1994","source":"Autoimmunity","url":"https://pubmed.ncbi.nlm.nih.gov/7517709","citation_count":4,"is_preprint":false},{"pmid":"15579118","id":"PMC_15579118","title":"Content of the HMG-17 chromosomal protein in porcine tissues.","date":"2004","source":"Protein and peptide letters","url":"https://pubmed.ncbi.nlm.nih.gov/15579118","citation_count":4,"is_preprint":false},{"pmid":"2169420","id":"PMC_2169420","title":"Protein HMG-17 is hyper-expressed in rat glucagonoma. Single-step isolation and sequencing.","date":"1990","source":"European journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/2169420","citation_count":4,"is_preprint":false},{"pmid":"21988615","id":"PMC_21988615","title":"Ectopic expression of Hmgn2 antagonizes mouse erythroid differentiation in vitro.","date":"2012","source":"Cell biology international","url":"https://pubmed.ncbi.nlm.nih.gov/21988615","citation_count":3,"is_preprint":false},{"pmid":"40092489","id":"PMC_40092489","title":"HMGN2 accelerates the proliferation and cell cycle progression of glioblastoma by regulating CDC20 expression.","date":"2024","source":"Genes & diseases","url":"https://pubmed.ncbi.nlm.nih.gov/40092489","citation_count":3,"is_preprint":false},{"pmid":"37869664","id":"PMC_37869664","title":"HMGN2 and Histone H1.2: potential targets of a novel probiotic mixture for seasonal allergic rhinitis.","date":"2023","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/37869664","citation_count":3,"is_preprint":false},{"pmid":"12523645","id":"PMC_12523645","title":"Rabbit anti-HMG-17 antibodies recognize similar epitopes on the HMG-17 molecule as lupus autoantibodies. Relation with histone H1 defined epitopes.","date":"2002","source":"Journal of peptide science : an official publication of the European Peptide Society","url":"https://pubmed.ncbi.nlm.nih.gov/12523645","citation_count":3,"is_preprint":false},{"pmid":"16156270","id":"PMC_16156270","title":"[E. coli-based production of recombinant HMG-17 and its antibacterial domain].","date":"2005","source":"Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi","url":"https://pubmed.ncbi.nlm.nih.gov/16156270","citation_count":1,"is_preprint":false},{"pmid":"2226652","id":"PMC_2226652","title":"Expression of human chromosomal proteins HMG-14 and HMG-17 in Saccharomyces cerevisiae.","date":"1990","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/2226652","citation_count":1,"is_preprint":false},{"pmid":"8670211","id":"PMC_8670211","title":"Chromosomal proteins HMG-14 and HMG-17 are synthesized throughout the S-phase in Burkitt's lymphoma.","date":"1996","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/8670211","citation_count":1,"is_preprint":false},{"pmid":"40834970","id":"PMC_40834970","title":"Inhibition of HMGN2 SUMOylation ameliorates atherosclerosis by activating PAX5 expression to induce macrophage M2 polarization.","date":"2025","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/40834970","citation_count":0,"is_preprint":false},{"pmid":"20842856","id":"PMC_20842856","title":"[Isolation and purification of antimicrobial polypeptide HMGN2 from human lymph node and analysis of its distribution].","date":"2010","source":"Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi","url":"https://pubmed.ncbi.nlm.nih.gov/20842856","citation_count":0,"is_preprint":false},{"pmid":"41246296","id":"PMC_41246296","title":"Deficiency of HMGN2 enhances antibacterial activity of macrophages by promoting H3 histone modification-mediated CD14/iNOS expression.","date":"2025","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/41246296","citation_count":0,"is_preprint":false},{"pmid":"16294743","id":"PMC_16294743","title":"[Application of HMGN2-tag constructs to analysis of HMGN2 distribution in HeLa cells].","date":"2005","source":"Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi","url":"https://pubmed.ncbi.nlm.nih.gov/16294743","citation_count":0,"is_preprint":false},{"pmid":"39179658","id":"PMC_39179658","title":"An evolutionarily distinct Hmgn2 variant influences shape recognition in Medaka Fish.","date":"2024","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/39179658","citation_count":0,"is_preprint":false},{"pmid":"21866626","id":"PMC_21866626","title":"[Inhibitory effect of recombinant HMGN2 protein on human hepatitis B viral].","date":"2011","source":"Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition","url":"https://pubmed.ncbi.nlm.nih.gov/21866626","citation_count":0,"is_preprint":false},{"pmid":"28591948","id":"PMC_28591948","title":"[The Role of HMGN2 in the Development of Periodontitis Dental Plaque].","date":"2016","source":"Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition","url":"https://pubmed.ncbi.nlm.nih.gov/28591948","citation_count":0,"is_preprint":false},{"pmid":"41700809","id":"PMC_41700809","title":"Antitumor effects of STING agonists on nervous system tumors via tumor-intrinsic STING-STAT1-mediated HMGN2 expression.","date":"2026","source":"Cancer biology & medicine","url":"https://pubmed.ncbi.nlm.nih.gov/41700809","citation_count":0,"is_preprint":false},{"pmid":"41325801","id":"PMC_41325801","title":"HMGN1 and HMGN2 are recruited to acetylated and histone variant H2A.Z-containing nucleosomes to regulate chromatin state and transcription.","date":"2025","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/41325801","citation_count":0,"is_preprint":false},{"pmid":"10640150","id":"PMC_10640150","title":"Regional fine mapping of HMG17 to chromosomal band 1p35.","date":"2000","source":"Cancer genetics and cytogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/10640150","citation_count":0,"is_preprint":false},{"pmid":"16078558","id":"PMC_16078558","title":"[Production of HMGN2 polyclonal antibody by immunization with recombinant GST-HMGN2 fusion protein and its application to analysis of HMGN2 distribution in human monocytes].","date":"2005","source":"Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition","url":"https://pubmed.ncbi.nlm.nih.gov/16078558","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":43752,"output_tokens":7397,"usd":0.121106},"stage2":{"model":"claude-opus-4-6","input_tokens":11141,"output_tokens":4653,"usd":0.258045},"total_usd":0.379151,"stage1_batch_id":"msgbatch_01DzrsgVgYngY1hvM3DU1yF2","stage2_batch_id":"msgbatch_01KA9b7iRzKFdhoBUT7vCvSe","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"PCAF acetyltransferase specifically acetylates HMGN2 (HMG-17) at lysine 2, and this acetylation reduces the affinity of HMGN2 for nucleosome cores; conversely, nucleosome-bound HMGN2 inhibits PCAF-mediated acetylation of histone H3.\",\n      \"method\": \"In vitro acetyltransferase assay, mass spectrometry sequence analysis, equilibrium dialysis, competition studies with deletion mutants\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — in vitro reconstitution with mutagenesis and mass spectrometry, multiple orthogonal methods in single study\",\n      \"pmids\": [\"10207070\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"HMGN2 (HMG-17) acts as a chromatin-specific transcriptional coactivator that increases the efficiency of RNA polymerase II transcription initiation (7- to 40-fold stimulation) only from nucleosomal chromatin templates assembled with the protein, not from protein-free DNA or post-assembly added protein.\",\n      \"method\": \"In vitro chromatin assembly and transcription assay with regularly spaced nucleosomal arrays, GAL4-VP16 activator, structural analysis\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — reconstituted chromatin transcription system with rigorous controls distinguishing initiation vs. elongation\",\n      \"pmids\": [\"7649479\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1993,\n      \"finding\": \"HMGN2 (HMG-17) is incorporated into nascent chromatin during replication in a cell-free Xenopus egg system, stabilizes nucleosomal core structure, improves nucleosomal periodicity, and significantly increases transcriptional potential only when incorporated during (not after) chromatin assembly.\",\n      \"method\": \"Cell-free Xenopus egg extract chromatin assembly, transcription assays with 5S RNA gene and satellite I chromatin, kinetic studies\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — cell-free reconstitution with kinetic controls, multiple templates\",\n      \"pmids\": [\"8404854\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"HMGN2 (HMG-17) stimulates replication efficiency of chromatin templates (SV40 minichromosomes) only when incorporated during chromatin assembly, not post-assembly, and only from chromatin templates, not protein-free DNA; the effect is associated with induction of extended chromatin structure.\",\n      \"method\": \"In vitro SV40 replication system, minichromosome assembly in Xenopus egg extracts, structural analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — in vitro reconstitution with rigorous controls for timing of incorporation\",\n      \"pmids\": [\"9545265\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"Hydroxyl radical footprinting mapped HMGN2 (HMG-17) binding sites on nucleosome cores: two molecules bind per nucleosome, protecting DNA ~25 bp from the end of the core and near the nucleosomal dyad axis, bridging two adjacent DNA strands on the surface, with binding sites overlapping those of linker histones near the dyad.\",\n      \"method\": \"Hydroxyl radical footprinting of nucleosome cores and H1/H5-depleted chromatosomes\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — direct structural footprinting assay with defined controls\",\n      \"pmids\": [\"8107104\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1992,\n      \"finding\": \"The nucleosome-binding domain of HMGN2 (HMG-17) — a 30 amino acid peptide — functions as an independent module: it specifically shifts nucleosome core mobility, elevates thermal denaturation of cores, protects the same DNase I sites as intact protein, and requires histone tails for binding.\",\n      \"method\": \"Mobility shift assays, thermal denaturation, DNase I digestion, trypsin digestion of histone tails with synthetic peptides and recombinant protein\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — multiple orthogonal in vitro assays with domain-mapping peptides\",\n      \"pmids\": [\"1453455\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"HMGN2 (HMG-17) is released from chromatin during mitosis (metaphase/anaphase), then re-imported into the nucleus in late telophase via active nuclear import requiring energy and importin alpha; the protein contains an intrinsic bipartite nuclear localization signal.\",\n      \"method\": \"Immunofluorescence colocalization through cell cycle, reconstituted nuclei and permeabilized cell import assays, energy depletion experiments\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct localization experiments with functional import assays and mechanistic dissection\",\n      \"pmids\": [\"9852141\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"HMGN2 (HMG-17) colocalizes with sites of active RNA polymerase II transcription; a peptide corresponding to the nucleosomal binding domain of HMG-14/17 displaces HMGN2 from chromatin and arrests pol II transcription; upon transcriptional inhibition, HMGN2 redistributes from chromatin to interchromatin granule clusters (SC35-positive).\",\n      \"method\": \"Immunofluorescence in tissue culture cells, peptide microinjection into permeabilized cells, alpha-amanitin and actinomycin D treatment\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct localization coupled to functional perturbation, multiple inhibitors tested\",\n      \"pmids\": [\"9843505\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"HMGN2 (HMG-17) physically interacts with the PITX2 homeodomain protein to inhibit its DNA-binding activity; beta-catenin forms a ternary PITX2/HMGN2/beta-catenin complex that switches HMGN2 from a transcriptional repressor to an activator; HMG-17 homozygous knockout mice show early embryonic lethality.\",\n      \"method\": \"Co-immunoprecipitation, EMSA, reporter assays, pull-down, confocal microscopy, homozygous knockout mouse model\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal co-IP, functional EMSA, in vivo knockout, multiple methods\",\n      \"pmids\": [\"18045789\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"HMGN2 inducibly binds a novel transactivation domain in nuclear prolactin receptor (PRLr) in a phosphorylation-dependent manner; the HMGN2-PRLr interaction enables Stat5a-responsive promoter binding and transcriptional activation, promoting anchorage-independent growth.\",\n      \"method\": \"Co-immunoprecipitation, ChIP assays, reporter assays, soft agar anchorage-independent growth assay\",\n      \"journal\": \"Molecular endocrinology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP with functional ChIP and cell biology readout\",\n      \"pmids\": [\"21816901\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"HDAC6 deacetylates HMGN2 at lysine K2; deacetylation of HMGN2 promotes Stat5a-mediated transcription and breast cancer growth; HDAC6 inhibition increases HMGN2 acetylation and reduces Stat5a signaling in vitro and in vivo.\",\n      \"method\": \"HDAC6 inhibitor treatment in vitro and in vivo, acetylation Western blot, Stat5a target gene expression, breast cancer growth assays\",\n      \"journal\": \"Molecular cancer research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — writer/eraser identified with in vitro and in vivo functional consequence, replicated with pharmacological and genetic approaches\",\n      \"pmids\": [\"27358110\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"HMGN2 promotes STAT5 accessibility at prolactin-responsive promoter DNA by facilitating dissociation of linker histone H1; H1 knockdown rescues decreases in PRL-induced transcription caused by HMGN2 knockdown, demonstrating that HMGN2 acts antagonistically to H1 to enable STAT5 chromatin recruitment.\",\n      \"method\": \"siRNA knockdown of HMGN2 and H1, ChIP for STAT5 and H1, gene expression analysis, cell proliferation assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — epistasis by double knockdown with rescue, ChIP-based chromatin occupancy measurements\",\n      \"pmids\": [\"28035005\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"HMGN2 is SUMOylated at lysines K17 and K35 (within the nucleosome-binding domain) by SUMO E3 ligase PIAS1; SENP1 deSUMOylates HMGN2; SUMOylation decreases HMGN2 binding affinity to nucleosome core particles.\",\n      \"method\": \"In vitro SUMOylation assay, identification of SUMOylated residues by mutagenesis, SUMO1-conjugated HMGN2 reconstituted in E. coli, nucleosome binding assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — reconstituted SUMOylation system with in vitro nucleosome binding assay, writer/eraser identified with site mutagenesis\",\n      \"pmids\": [\"24872413\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"HMGN2 is a component of the global genome repair subpathway of nucleotide excision repair (NER): DT40 cells lacking HMGN2 are hypersensitive to UV irradiation, show increased G2-M checkpoint arrest and apoptosis, and have slower removal of UV-induced DNA lesions from native chromatin, though nucleotide excision repair per se (measured by host cell reactivation) remains intact.\",\n      \"method\": \"Gene knockout in DT40 cells, UV sensitivity assays, apoptosis and cell cycle analysis, host cell reactivation assay, DNA lesion removal kinetics\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined cellular phenotype and mechanistic dissection separating global genome repair from NER per se\",\n      \"pmids\": [\"19843163\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Loss of HMGN2 in pluripotent embryonal carcinoma cells leads to global reduction in H3K9 acetylation and disrupts H3K4me3, H3K9ac, H3K27ac, and H3K122ac at Nanog and Oct4 loci, causing loss of pluripotency markers and increased spontaneous neuronal differentiation.\",\n      \"method\": \"HMGN2 knockout cell lines, ChIP-seq for histone marks, gene expression analysis, differentiation marker assays\",\n      \"journal\": \"Epigenetics & chromatin\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — KO with ChIP-seq profiling of multiple histone modifications, defined cellular phenotype\",\n      \"pmids\": [\"31831052\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Lysine succinylation at K30 within the HMGN2 nucleosome-binding domain (installed via a succinyl lysine analogue) significantly decreases HMGN2 binding to mononucleosomes and promotes nucleosomal DNA unwrapping at entry/exit regions, increasing DNA accessibility.\",\n      \"method\": \"Site-specific incorporation of succinyl lysine analogue, mononucleosome binding assays, nucleosomal DNA accessibility assays\",\n      \"journal\": \"RSC chemical biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — site-specific PTM mimetic reconstituted in vitro with nucleosome binding and DNA accessibility assays\",\n      \"pmids\": [\"34458839\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Binding of HMGN2 to reconstituted nucleosomes increases the winding angle of nucleosomal DNA (measured by circular dichroism), with the extent of structural change differing from that of HMGN1, suggesting distinct abilities to facilitate nucleosome remodeling.\",\n      \"method\": \"CD spectroscopy of nucleosomes reconstituted from unmodified recombinant histones and synthetic positioning DNA, with purified HMGN1 and HMGN2\",\n      \"journal\": \"FEBS open bio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — in vitro reconstitution with spectroscopic readout, single lab, single method\",\n      \"pmids\": [\"23772392\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"HMGN2 promotes LPS-induced beta-defensin-2 expression in A549 cells by prolonging nuclear retention of NF-κB p65, enhancing p65 acetylation, increasing histone acetyltransferase activity, and promoting p65-Ser536 phosphorylation; ChIP shows HMGN2 and p65 synergistically bind the HBD-2 promoter.\",\n      \"method\": \"siRNA knockdown, ChIP, Western blot for p65 nuclear retention and phosphorylation, HAT activity assay, reporter assay\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — ChIP and multiple signaling readouts, single lab\",\n      \"pmids\": [\"21518253\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"HMGN2 interacts with transcription factor Lef-1 through its HMG-box domain and with Dlx2, FoxJ1, and Pitx2; HMGN2 binding to Lef-1 inhibits Lef-1 DNA-binding activity; HMGN2 associates with H4K5ac and H3K4me2 marks at the Dlx2 promoter; miR-23a/b directly target Hmgn2 to post-transcriptionally suppress its expression; Hmgn2 ablation in mice increases amelogenin expression due to increased transcriptional activity of Pitx2, Dlx2, Lef-1, and FoxJ1.\",\n      \"method\": \"Bimolecular fluorescence complementation, pull-down, co-immunoprecipitation, EMSA, ChIP, mouse knockout, in situ hybridization, luciferase reporter assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal methods including EMSA, ChIP, Co-IP, in vivo knockout with defined phenotype\",\n      \"pmids\": [\"35872015\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"HMGN1 and HMGN2 preferentially bind nucleosomes with acetylated H3 tail residues and H2A.Z-containing nucleosomes; HMGN1/HMGN2 binding to nucleosomes reduces p300-mediated acetylation of H3K18, H3K23, and H3K27; Hmgn1/Hmgn2 double-knockout mESCs show increased H3K27me2/me3 and altered expression of ~1000 genes.\",\n      \"method\": \"Nucleosome binding assays, in vitro p300 acetylation assays, epiproteomic mass spectrometry, RNA-seq in CRISPR-engineered knockout mESCs\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — in vitro reconstitution with PTM-modified nucleosomes, acetylation assay with p300, epiproteomic MS in KO cells\",\n      \"pmids\": [\"41325801\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1987,\n      \"finding\": \"HMGN2 (HMG17) is present only downstream of transcription start sites in active chromatin of vitellogenin II, lysozyme, and ovalbumin genes, as demonstrated by immunofractionation of oligonucleosomes with monoclonal antibodies and analysis by two independent experimental approaches.\",\n      \"method\": \"Monoclonal antibody immunoisolation of oligonucleosomes, gene-specific DNA probe analysis of active chromatin from chicken liver and oviduct\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — two independent experimental approaches with gene-specific resolution\",\n      \"pmids\": [\"3665881\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1984,\n      \"finding\": \"HMG17 (HMGN2) greatly facilitates catenation of double-stranded DNA rings by DNA topoisomerases types I and II, promoting formation of large catenated networks even at low DNA concentrations where catenanes are otherwise absent.\",\n      \"method\": \"In vitro topoisomerase catenation assay, gel electrophoresis, electron microscopy, restriction enzyme cleavage\",\n      \"journal\": \"Archives of biochemistry and biophysics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — in vitro reconstitution with multiple topoisomerases, single lab\",\n      \"pmids\": [\"6326673\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"HMGN2 (HMG-17) nucleosomes are organized in clusters of ~6 contiguous HMG-17-containing nucleosomes in cellular chromatin, and nucleosomes containing HMG-17 are devoid of HMG-14 (the two segregate into distinct nuclear domains), as shown by immunofractionation and confocal immunofluorescence.\",\n      \"method\": \"Confocal immunofluorescence microscopy, immunofractionation with affinity-purified antibodies, quantitative analysis\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct imaging and biochemical fractionation, single lab\",\n      \"pmids\": [\"9417927\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Butyrate-induced hyperacetylation of HMGN2 alters its binding properties to chromatin in HT29 colon adenocarcinoma cells: acetylated HMGN2 is solubilized from chromatin, as demonstrated by FRAP of HMG-N2-EGFP fusion proteins and solubilization of endogenous acetylated HMGN2 in permeabilized cells.\",\n      \"method\": \"Butyrate treatment, transfected EGFP fusion protein dynamics, solubilization of acetylated HMGN2 from permeabilized cells, Northern and Western blot\",\n      \"journal\": \"International journal of cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — live cell imaging with EGFP fusion and biochemical fractionation, single lab\",\n      \"pmids\": [\"11807779\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"HMGN2 binds to histones and promotes stability of H3K27ac at the CDC20 promoter region, enhancing CDC20 transcriptional activity and accelerating glioma cell proliferation; HMGN2 knockout reduces CDC20 expression and cell cycle progression.\",\n      \"method\": \"ChIP for H3K27ac at CDC20 promoter, HMGN2 knockdown/knockout, gene expression and cell proliferation assays\",\n      \"journal\": \"Genes & diseases\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — ChIP with functional KO, single lab\",\n      \"pmids\": [\"40092489\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SUMOylated HMGN2 (via PIAS1) enhances interaction with transcription factor PAX5, inhibiting PAX5 activity and driving macrophage M1 polarization; PIAS1 knockdown reduces HMGN2 SUMOylation, restoring PAX5-mediated M2 polarization and suppressing NF-κB inflammatory signaling in atherosclerosis.\",\n      \"method\": \"Co-immunoprecipitation, PIAS1 knockdown, foam macrophage model, ApoE-/- mouse model, ELISA, Western blot, immunofluorescence\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — Co-IP with in vivo model, single lab, functional readout through macrophage polarization\",\n      \"pmids\": [\"40834970\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"HMGN2 exhibits antimicrobial activity against Gram-negative bacteria and Candida; the alpha-helical domain (residues 18-48) is essential and sufficient for antimicrobial activity, while N-terminal and C-terminal fragments are inactive.\",\n      \"method\": \"In vitro antimicrobial assays (MIC, MBC) with recombinant full-length and domain fragments, synthetic peptides\",\n      \"journal\": \"Acta pharmacologica Sinica\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — in vitro domain mapping with recombinant and synthetic peptides, single lab\",\n      \"pmids\": [\"16115376\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"HMGN2 facilitates Nrf2 nuclear translocation upon pyocyanin stimulation in A549 cells, elevating antioxidant gene expression and reducing ROS; HMGN2 also regulates actin cytoskeleton rearrangement to attenuate Pseudomonas aeruginosa internalization via ROS elimination.\",\n      \"method\": \"HMGN2 knockdown/overexpression, ROS measurement, Nrf2 nuclear fractionation, actin staining, bacterial invasion assays\",\n      \"journal\": \"Free radical biology & medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss- and gain-of-function with multiple mechanistic readouts, single lab\",\n      \"pmids\": [\"28408162\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"HMGN2 deficiency in macrophages promotes M1 polarization during NTM infection by enhancing activation of NF-κB and MAPK signaling, leading to increased iNOS, IFNγ, TNF-α, IL-1β, IL-6 expression and NO production, which affects NTM survival.\",\n      \"method\": \"siRNA knockdown, macrophage polarization marker analysis, NF-κB/MAPK signaling assays, intracellular bacterial survival assay\",\n      \"journal\": \"Journal of cellular and molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function with defined signaling pathway readout, single lab\",\n      \"pmids\": [\"31596045\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"HMGN2 acts as a positive regulator of LPS-induced mouse beta-defensin-3 and -4 expression in vivo; HMGN2 shRNA interference reduces mBD-3 and mBD-4 but not mBD-1 expression in maternal, embryonic, and neonatal mouse tissues upon LPS stimulation.\",\n      \"method\": \"shRNA knockdown in vivo in pregnant ICR mice, real-time PCR for defensin and HMGN2 expression across developmental timepoints and tissues\",\n      \"journal\": \"Inflammation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vivo knockdown with gene-specific phenotypic readout, single lab\",\n      \"pmids\": [\"21594618\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"HMGN2 knockdown in A549 cells increases α5β1 integrin expression on cell membranes, talin expression, FAK and Src phosphorylation, and actin polymerization, resulting in increased Klebsiella pneumoniae internalization.\",\n      \"method\": \"siRNA knockdown, cDNA microarray, flow cytometry for integrin surface expression, phospho-Western blot, bacterial invasion assay\",\n      \"journal\": \"International journal of molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — siRNA KD with signaling pathway dissection, single lab\",\n      \"pmids\": [\"27460641\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"HMGN2 knockout in RAW264.7 macrophages enhances bactericidal and phagocytic activity by transcriptionally promoting CD14 expression via increased H3K4me3, H3K9ac, and H3K27ac at the CD14 gene promoter, activating CD14-mediated MAPK signaling and NO production.\",\n      \"method\": \"CRISPR-Cas9 knockout, ChIP for histone marks at CD14 promoter, bacterial killing assays, MAPK signaling analysis\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — CRISPR KO with ChIP-based mechanistic dissection, single lab\",\n      \"pmids\": [\"41246296\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"HMGN2 is a nucleosome-binding protein that binds to the nucleosomal core (via a 30-aa nucleosome-binding domain requiring histone tails) and acts as a chromatin architectural element: it unfolds higher-order chromatin structure to enhance RNA polymerase II transcription initiation and DNA replication from chromatin templates; its chromatin affinity and activity are modulated by post-translational modifications (acetylation by PCAF at K2, deacetylation by HDAC6, SUMOylation by PIAS1 at K17/K35, and succinylation at K30, all of which reduce nucleosome binding), and it preferentially associates with acetylated H3 and H2A.Z-containing nucleosomes to regulate active chromatin states and suppress repressive H3K27 methylation; HMGN2 also functions as a molecular switch regulating homeodomain and other transcription factor activity through direct protein interactions, modulates NF-κB and Nrf2 signaling in innate immune responses, and exhibits extranuclear antimicrobial activity through its alpha-helical domain.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"HMGN2 is a nucleosome-binding chromatin architectural protein that modulates higher-order chromatin structure to regulate transcription, replication, and DNA repair. Its 30-amino-acid nucleosome-binding domain contacts two sites per nucleosome core near the dyad axis and entry/exit regions, requiring histone tails for binding and antagonizing linker histone H1 occupancy; incorporation during chromatin assembly unfolds chromatin and enhances RNA polymerase II transcription initiation and DNA replication from nucleosomal templates [PMID:7649479, PMID:9545265, PMID:8107104, PMID:1453455, PMID:28035005]. HMGN2 preferentially associates with acetylated H3 and H2A.Z-containing nucleosomes, maintains active histone marks (H3K27ac, H3K9ac, H3K4me3) at target loci, suppresses H3K27 methylation, and its chromatin binding is negatively regulated by acetylation at K2 (written by PCAF, erased by HDAC6), SUMOylation at K17/K35 (by PIAS1), and succinylation at K30 [PMID:10207070, PMID:41325801, PMID:24872413, PMID:34458839, PMID:27358110]. Beyond its chromatin role, HMGN2 directly interacts with homeodomain transcription factors (PITX2, Lef-1, Dlx2) to inhibit their DNA binding, modulates NF-κB and Nrf2 signaling in innate immune responses, and its alpha-helical domain possesses intrinsic antimicrobial activity against Gram-negative bacteria [PMID:18045789, PMID:35872015, PMID:21518253, PMID:16115376, PMID:31596045].\",\n  \"teleology\": [\n    {\n      \"year\": 1984,\n      \"claim\": \"Early work established that HMGN2 alters DNA topology by facilitating topoisomerase-mediated catenation, indicating a role in modulating DNA structure beyond simple binding.\",\n      \"evidence\": \"In vitro topoisomerase catenation assay with purified HMG-17\",\n      \"pmids\": [\"6326673\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab, single method\", \"Physiological relevance of catenation-promoting activity unclear\", \"No chromatin context tested\"]\n    },\n    {\n      \"year\": 1987,\n      \"claim\": \"Immunofractionation of oligonucleosomes revealed that HMGN2 is selectively enriched downstream of transcription start sites in active genes, establishing its association with transcriptionally active chromatin domains.\",\n      \"evidence\": \"Monoclonal antibody immunoisolation of oligonucleosomes from chicken liver and oviduct with gene-specific probes\",\n      \"pmids\": [\"3665881\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Causal relationship between HMGN2 presence and transcription not tested\", \"Mechanism of preferential deposition at active genes unknown\"]\n    },\n    {\n      \"year\": 1992,\n      \"claim\": \"Mapping of the nucleosome-binding domain to a 30-amino-acid peptide that autonomously recognizes nucleosome cores and requires histone tails defined the minimal structural module for HMGN2–chromatin interaction.\",\n      \"evidence\": \"Mobility shift, thermal denaturation, DNase I footprinting, and trypsin digestion with synthetic peptides and recombinant protein\",\n      \"pmids\": [\"1453455\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Specific histone tail residues required not identified\", \"No structure of the domain–nucleosome complex\"]\n    },\n    {\n      \"year\": 1993,\n      \"claim\": \"Cell-free chromatin assembly experiments demonstrated that HMGN2 must be incorporated during replication-coupled assembly to enhance transcription, revealing that it acts as a constitutive chromatin component rather than a post-hoc modifier.\",\n      \"evidence\": \"Xenopus egg extract chromatin assembly with transcription assays on 5S RNA gene and satellite I templates\",\n      \"pmids\": [\"8404854\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of co-assembly incorporation unknown\", \"Whether replication-independent assembly also suffices not tested\"]\n    },\n    {\n      \"year\": 1994,\n      \"claim\": \"Hydroxyl radical footprinting resolved the precise binding geometry: two HMGN2 molecules bind per nucleosome near the dyad and ~25 bp from core DNA ends, overlapping linker histone sites, explaining how HMGN2 and H1 compete for the same nucleosome.\",\n      \"evidence\": \"Hydroxyl radical footprinting of nucleosome cores and H1/H5-depleted chromatosomes\",\n      \"pmids\": [\"8107104\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No atomic-resolution structure\", \"How two HMGN2 molecules cooperatively bind is not resolved\"]\n    },\n    {\n      \"year\": 1995,\n      \"claim\": \"Reconstituted chromatin transcription assays quantified a 7–40-fold stimulation of RNA polymerase II transcription initiation, establishing HMGN2 as a bona fide chromatin-specific transcriptional coactivator.\",\n      \"evidence\": \"In vitro transcription from regularly spaced nucleosomal arrays with GAL4-VP16 activator\",\n      \"pmids\": [\"7649479\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether elongation is also affected was not resolved\", \"Generality across diverse promoters not tested\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Discovery that HMGN2-containing nucleosomes cluster in contiguous runs of ~6 and are mutually exclusive with HMGN1 revealed that HMGN variants define distinct chromatin domains rather than being randomly distributed.\",\n      \"evidence\": \"Immunofractionation and confocal immunofluorescence microscopy\",\n      \"pmids\": [\"9417927\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Mechanism of domain segregation unknown\", \"Functional consequence of clustering not tested\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Three concurrent studies resolved HMGN2 dynamics and function: it colocalizes with active pol II sites, is released from chromatin during mitosis and re-imported via importin-α in telophase, and stimulates SV40 replication efficiency only from chromatin assembled with the protein.\",\n      \"evidence\": \"Immunofluorescence through cell cycle, nuclear import assays, peptide microinjection, SV40 minichromosome replication\",\n      \"pmids\": [\"9852141\", \"9843505\", \"9545265\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether mitotic release serves a regulatory function or is passive is unknown\", \"Replication stimulation mechanism at the molecular level unresolved\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Identification of PCAF as the acetyltransferase that acetylates K2, with acetylation reducing nucleosome affinity, established the first post-translational switch controlling HMGN2–chromatin interaction; reciprocally, nucleosome-bound HMGN2 inhibits PCAF acetylation of H3.\",\n      \"evidence\": \"In vitro acetyltransferase assay, mass spectrometry, equilibrium dialysis\",\n      \"pmids\": [\"10207070\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo dynamics of K2 acetylation not characterized\", \"Identity of additional acetyltransferases not excluded\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Domain mapping revealed that the alpha-helical region (residues 18–48, overlapping the nucleosome-binding domain) has direct antimicrobial activity against Gram-negative bacteria and Candida, indicating an extranuclear function.\",\n      \"evidence\": \"In vitro MIC/MBC assays with recombinant fragments and synthetic peptides\",\n      \"pmids\": [\"16115376\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"In vivo antimicrobial relevance not demonstrated\", \"Mechanism of membrane disruption not characterized\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Discovery that HMGN2 directly inhibits PITX2 DNA binding, with β-catenin converting the complex into a transcriptional activator, and that homozygous HMGN2 knockout mice are embryonic lethal, established HMGN2 as a molecular switch for homeodomain transcription factor activity essential for development.\",\n      \"evidence\": \"Co-IP, EMSA, reporter assays, confocal microscopy, homozygous knockout mouse\",\n      \"pmids\": [\"18045789\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stage and cause of embryonic lethality not defined\", \"Whether all homeodomain interactions share the same mechanism unclear\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"HMGN2 knockout DT40 cells showed impaired removal of UV-induced lesions from chromatin without affecting core NER catalysis, demonstrating that HMGN2 facilitates the global genome repair subpathway through chromatin accessibility rather than repair enzyme function.\",\n      \"evidence\": \"DT40 gene knockout, UV sensitivity, host cell reactivation, DNA lesion kinetics\",\n      \"pmids\": [\"19843163\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of chromatin opening for NER factors not defined\", \"Mammalian confirmation not provided\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Two studies connected HMGN2 to innate immune transcriptional regulation: it promotes LPS-induced β-defensin-2 expression by enhancing NF-κB p65 nuclear retention and acetylation, and binds nuclear prolactin receptor in a phosphorylation-dependent manner to enable Stat5a-driven transcription.\",\n      \"evidence\": \"siRNA knockdown with ChIP, reporter assays, HAT activity measurement; Co-IP and ChIP for Stat5a promoter binding\",\n      \"pmids\": [\"21518253\", \"21816901\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single labs for each study\", \"Whether HMGN2–p65 interaction is direct or chromatin-mediated unclear\", \"In vivo relevance of PRLr interaction not established\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identification of PIAS1-mediated SUMOylation at K17 and K35 within the nucleosome-binding domain, reversed by SENP1, provided a second PTM switch that reduces nucleosome affinity, paralleling acetylation at K2.\",\n      \"evidence\": \"In vitro SUMOylation with site mutagenesis, reconstituted nucleosome binding assays\",\n      \"pmids\": [\"24872413\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo SUMOylation dynamics and downstream transcriptional consequences not characterized\", \"Interplay between SUMOylation and acetylation not tested\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"The acetyltransferase/deacetylase cycle at K2 was completed by identifying HDAC6 as the eraser; deacetylation promotes Stat5a transcription and breast cancer growth, linking HMGN2 PTM status to oncogenic signaling. Concurrently, epistasis experiments showed HMGN2 antagonizes linker histone H1 to enable STAT5 chromatin access.\",\n      \"evidence\": \"HDAC6 inhibitor treatment in vitro/in vivo with Stat5a target gene readouts; double knockdown of HMGN2 and H1 with ChIP\",\n      \"pmids\": [\"27358110\", \"28035005\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether HDAC6-HMGN2 axis operates in non-breast contexts unknown\", \"Structural basis for H1–HMGN2 competition at specific loci not resolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Loss of HMGN2 in embryonal carcinoma cells globally reduced H3K9ac and disrupted active marks at pluripotency loci (Nanog, Oct4), causing spontaneous neuronal differentiation and establishing HMGN2 as a guardian of the active chromatin landscape required for pluripotency.\",\n      \"evidence\": \"HMGN2 knockout cell lines, ChIP-seq for multiple histone marks, differentiation marker analysis\",\n      \"pmids\": [\"31831052\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether effect is direct binding at pluripotency loci or indirect global chromatin change unresolved\", \"In vivo embryonic stem cell confirmation lacking\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Site-specific succinylation at K30 in the nucleosome-binding domain was shown to decrease nucleosome binding and promote DNA unwrapping at entry/exit sites, adding a third class of PTM that regulates HMGN2–nucleosome interaction.\",\n      \"evidence\": \"Succinyl lysine analogue incorporation with mononucleosome binding and DNA accessibility assays\",\n      \"pmids\": [\"34458839\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological writer/eraser for K30 succinylation not identified\", \"In vivo prevalence of K30 succinylation unknown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"HMGN2 was shown to interact with and inhibit Lef-1 DNA binding in addition to PITX2, Dlx2, and FoxJ1, with Hmgn2 ablation in mice increasing amelogenin expression; miR-23a/b were identified as post-transcriptional regulators of Hmgn2, broadening the homeodomain switch model and revealing upstream control of HMGN2 levels.\",\n      \"evidence\": \"BiFC, pull-down, Co-IP, EMSA, ChIP, mouse knockout, luciferase reporters\",\n      \"pmids\": [\"35872015\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether miR-23a/b regulation is tissue-specific not determined\", \"Structural basis for homeodomain recognition by HMGN2 unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Two studies extended HMGN2 biology: it preferentially binds acetylated-H3 and H2A.Z nucleosomes, limits p300-mediated H3K27 acetylation, and suppresses H3K27me2/me3 (with HMGN1); separately, PIAS1-mediated SUMOylation of HMGN2 enhances its interaction with PAX5 to drive macrophage M1 polarization and NF-κB signaling in atherosclerosis.\",\n      \"evidence\": \"Reconstituted nucleosome binding with modified histones, p300 acetylation assay, epiproteomic MS in CRISPR KO mESCs; Co-IP with PIAS1 knockdown in ApoE−/− mouse model\",\n      \"pmids\": [\"41325801\", \"40834970\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How HMGN2 binding to acetylated nucleosomes mechanistically suppresses H3K27me3 not resolved\", \"Whether SUMOylation-dependent PAX5 interaction occurs genome-wide unknown\", \"Relative contributions of HMGN1 vs HMGN2 to H3K27me3 suppression not separated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"No high-resolution structure of HMGN2 bound to a nucleosome exists, the mechanism by which HMGN2 is selectively deposited into active chromatin domains during replication is unknown, and how multiple PTM switches (acetylation, SUMOylation, succinylation) are coordinated in vivo to tune chromatin architecture remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No atomic structure of HMGN2–nucleosome complex\", \"Mechanism of replication-coupled chromatin incorporation unknown\", \"Combinatorial PTM regulation in vivo not addressed\", \"Cause of embryonic lethality in knockout mice not defined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [4, 5, 15, 16, 19]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [1, 8, 11, 17, 18, 25]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1, 8, 9, 11, 18, 24]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [4, 5, 7, 20, 22]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [6, 7, 9]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [4, 14, 19]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [1, 7, 8, 9, 11, 14, 24]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [2, 3, 14, 15, 16, 19]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [13]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [17, 25, 28, 29, 31]},\n      {\"term_id\": \"R-HSA-69306\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PITX2\",\n      \"LEF1\",\n      \"PCAF\",\n      \"HDAC6\",\n      \"PIAS1\",\n      \"PRLR\",\n      \"PAX5\",\n      \"CTNNB1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}