{"gene":"HMGN1","run_date":"2026-06-10T01:55:22","timeline":{"discoveries":[{"year":1980,"finding":"HMGN1 (HMG-14) binds specifically to nucleosome core particles with two molecules per core; its affinity for core particles is greater than for histone-free DNA of core size, and binding sites are located near the ends of the nucleosome core DNA. Nucleosome-HMG complexes are enriched in transcriptionally active gene sequences.","method":"Thermal denaturation, nuclease digestion, nucleosome binding assays with chicken erythrocyte chromatin","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Strong — multiple orthogonal biochemical methods (thermal denaturation, nuclease digestion, DNA sequence enrichment), replicated across multiple labs in this era","pmids":["6449690"],"is_preprint":false},{"year":1980,"finding":"HMG-14 is intrinsically disordered in free solution (assessed by NMR and CD), binds DNA via its N-terminal half at low ionic strength, and is released at 0.3 M NaCl (matching chromatin extraction conditions).","method":"270-MHz NMR, circular dichroism","journal":"European journal of biochemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — NMR and CD in single study, no functional mutagenesis validation","pmids":["6257511"],"is_preprint":false},{"year":1981,"finding":"HMGN1 (HMG-14) preferentially binds single-stranded DNA over double-stranded DNA, as demonstrated by sequential affinity chromatography.","method":"Sequential affinity chromatography on immobilized ss- and ds-DNA columns with purified protein","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct biochemical binding assay with purified protein, single lab, single method","pmids":["7279673"],"is_preprint":false},{"year":1985,"finding":"HMGN1 (HMG-14) contacts histones H2A, H2B, and H1, as well as DNA, within nucleosomes, as identified by chemical crosslinking with photoactivable heterobifunctional reagents in reconstituted chromatin.","method":"Reconstitution and chemical crosslinking with photoactivable reagents in chromatin","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct crosslinking in reconstituted chromatin, single lab, single method","pmids":["4074344"],"is_preprint":false},{"year":1994,"finding":"HMGN1 (HMG-14) maps the footprint on nucleosome cores at two positions: 25 bp from the end of core DNA and in each of the two major grooves flanking the dyad axis, bridging two adjacent DNA strands. The chromatin footprint of HMG-14 is indistinguishable from HMG-17.","method":"Hydroxyl radical footprinting of HMG-14/-17 on nucleosome cores and chromatosomes","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — hydroxyl radical footprinting (high-resolution structural method) with both H1-containing and H1-depleted particles, single lab but multiple particle types","pmids":["8107104"],"is_preprint":false},{"year":1994,"finding":"HMGN1 (HMG-14) stimulates the rate of RNA polymerase II elongation on chromatin templates but not on naked DNA, establishing that its effect on transcription is nucleosome-dependent.","method":"In vitro transcription assays on in vivo-assembled chromatin templates vs. DNA templates","journal":"Science (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 1 / Moderate — reconstituted in vitro transcription assay on chromatin vs. DNA, directly tests mechanism, single lab with clear positive and negative controls","pmids":["8047885"],"is_preprint":false},{"year":1994,"finding":"Upon mitogenic or stress stimulation, HMG-14 (HMGN1) is phosphorylated in its basic N-terminal domain on mononucleosome-associated protein by a mitogen-activated kinase; the phosphorylation is transient, quantitative, and occurs independently of transcription.","method":"In vivo phosphorylation mapping, micrococcal nuclease fractionation, in vitro kinase assay on isolated mononucleosomes","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro kinase assay on isolated mononucleosomes plus in vivo site mapping, single lab, multiple orthogonal approaches","pmids":["7925294"],"is_preprint":false},{"year":1994,"finding":"Single point mutations in the nucleosomal binding domain of HMGN1 (A21P or K26C) reduce cooperative binding to nucleosome cores 6.7- and 3-fold respectively, while non-cooperative binding is minimally affected, indicating a conformational change upon cooperative binding.","method":"Site-directed mutagenesis + nucleosome core binding assays","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct mutagenesis with quantitative binding assay, multiple mutants tested, single lab","pmids":["7971283"],"is_preprint":false},{"year":1997,"finding":"The acidic C-terminal region of HMG-14 (HMGN1) is necessary and sufficient to alleviate histone H1-mediated transcriptional repression and partially disrupt H1-dependent chromatin compaction; these activities can be substituted by acidic regions from GAL4 or HMG-2.","method":"SV40 minichromosome transcription assays, chromatin compaction assays, domain-swap experiments","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — reconstituted minichromosome system with domain-swap controls, multiple readouts (transcription and chromatin structure), single lab","pmids":["9315642"],"is_preprint":false},{"year":1998,"finding":"The C-terminal chromatin-unfolding domain of HMG-14 (HMGN1) targets the N-terminal tail of histone H3 in nucleosomes, while the N-terminal domain of HMG-14 targets histone H2B, as demonstrated by protein photocrosslinking.","method":"Protein photocrosslinking in nucleosome cores","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct site-specific photocrosslinking mapping domain contacts, single lab, clear structural-functional correlation","pmids":["9576905"],"is_preprint":false},{"year":1998,"finding":"HMGN1 (HMG-14/-17) proteins are released from chromatin during mitosis (absent in metaphase/anaphase) and actively re-imported into the nucleus in late telophase through a process requiring energy, importin alpha, and the proteins' intrinsic bipartite nuclear localization signal.","method":"Immunofluorescence cell cycle analysis, reconstituted nuclei nuclear import assays, permeabilized cell import assays","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct live-cell imaging plus reconstituted nuclear import assays, multiple orthogonal methods, single lab","pmids":["9852141"],"is_preprint":false},{"year":2000,"finding":"The histone acetyltransferase p300 specifically acetylates HMGN1 (HMG-14) at 7 major sites (6 novel), including 3 within the nucleosomal binding domain and 4 near the bipartite NLS; acetylation of the nucleosomal binding domain weakens HMGN1's interaction with nucleosome cores.","method":"In vitro acetyltransferase assays with purified p300, mass spectrometry of acetylation sites, nucleosome binding assays with acetylated protein, in vivo acetylation analysis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — reconstituted in vitro acetylation with purified p300, site identification by MS, functional binding assay, in vivo validation, single lab with multiple orthogonal methods","pmids":["10753971"],"is_preprint":false},{"year":2002,"finding":"Mitotic phosphorylation of the nucleosomal binding domain (NBD) of HMGN1 prevents nuclear re-entry in late telophase and promotes interaction with specific 14-3-3 isoforms; this inhibition is due to the phosphorylation itself, not merely to the addition of negative charges.","method":"Immunofluorescence, in vitro nuclear import assays with microinjected WT and mutant proteins, affinity chromatography with recombinant proteins and mitotic cell extracts","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal protein binding assays, nuclear import reconstitution, mutant rescue in Hmgn1-/- cells, multiple orthogonal methods in single lab","pmids":["12215538"],"is_preprint":false},{"year":2003,"finding":"MSK1 and MSK2 are the major kinases responsible for mitogen- and stress-induced phosphorylation of HMGN1 (HMG-14) in fibroblasts, as shown by the severe reduction or abolition of HMG-14 phosphorylation in MSK1/MSK2 double-knockout mice.","method":"Genetic knockout (MSK1-/-, MSK2-/-, double KO mice), phosphorylation assays in Coffin-Lowry cells and mouse fibroblasts","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic epistasis using double-knockout animals, replicated across multiple cell types and genetic backgrounds","pmids":["12773393"],"is_preprint":false},{"year":2003,"finding":"HMGN1 enhances the rate of nucleotide excision repair (NER) of UV-induced photoproducts in chromatin by reducing higher-order chromatin compaction and increasing accessibility to damaged DNA; this activity requires both nucleosome binding and chromatin-unfolding functions of HMGN1.","method":"Hmgn1-/- MEFs UV sensitivity assay, photoproduct removal kinetics, host cell reactivation, NER pathway analysis, mutant HMGN1 rescue transfections, nuclease accessibility assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — KO cells + domain-specific mutant rescue + multiple orthogonal readouts (UV survival, photoproduct removal, nuclease accessibility), single lab","pmids":["12660172"],"is_preprint":false},{"year":2004,"finding":"HMGN1 reduces the rate of stress-induced phosphorylation of histone H3 at Ser10 by hindering kinase access to nucleosomal (but not free) H3; in Hmgn1-/- cells, steady-state H3-pS10 levels are elevated. HMGN1 itself is phosphorylated by anisomycin-induced kinases before H3, causing transient weakening of its chromatin binding.","method":"In vitro kinase assays on nucleosomal vs. free H3, Hmgn1-/- cell western analysis, in vivo phosphorylation kinetics","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstituted kinase assay on nucleosomes plus in vivo KO validation, multiple orthogonal approaches, single lab","pmids":["15327773"],"is_preprint":false},{"year":2005,"finding":"HMGN1 elevates H3K14 acetylation by enhancing HAT (PCAF) activity on nucleosomal, but not free, H3; loss of HMGN1 in Hmgn1-/- cells reduces H3K14ac, and wild-type but not chromatin-binding-deficient HMGN1 rescues this.","method":"In vitro PCAF acetyltransferase assays on nucleosomes vs. free H3, Hmgn1-/- cell rescue with WT vs. mutant HMGN1, western analysis of H3K14ac","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — reconstituted in vitro acetyltransferase assay on nucleosomes plus in vivo KO rescue with domain-specific mutant, multiple methods, single lab","pmids":["16096646"],"is_preprint":false},{"year":2005,"finding":"HMGN1 negatively regulates N-cadherin expression in MEFs; loss of HMGN1 increases N-cadherin levels leading to increased cell adhesiveness, motility and aggregation, and this is rescued by WT but not chromatin-binding-deficient HMGN1.","method":"Hmgn1-/- MEFs, DNA microarray, RT-PCR, western blot, mutant rescue, cell adhesion/motility assays","journal":"The FEBS journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO + rescue with domain-specific mutant, multiple gene expression and functional readouts, single lab","pmids":["16279949"],"is_preprint":false},{"year":2005,"finding":"Loss of HMGN1 increases sensitivity to ionizing radiation, elevates tumor burden, and disrupts G2-M checkpoint activation in fibroblasts; these defects are rescued by WT but not chromatin-binding-deficient HMGN1.","method":"Hmgn1-/- mouse model, ionizing radiation survival, tumor incidence, cell cycle checkpoint analysis, mutant rescue transfections","journal":"Cancer research","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo KO mouse model plus mechanistic domain-mutant rescue, multiple phenotypic readouts (radiation sensitivity, G2-M checkpoint, tumorigenesis)","pmids":["16061652"],"is_preprint":false},{"year":2006,"finding":"HMGN1 modulates phosphorylation of histone H2A at Ser1; in Hmgn1-/- cells, H2AS1ph levels are elevated throughout the cell cycle. In vitro, HMGN1 reduces Rsk2- and Msk1-mediated phosphorylation of nucleosomal but not free H2A, requiring HMGN1-chromatin binding.","method":"In vitro kinase assays with Rsk2 and Msk1 on nucleosomal vs. free H2A, Hmgn1-/- cell western analysis, chromatin-binding mutant controls","journal":"Biochemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — reconstituted in vitro kinase assay on nucleosomes plus KO validation, domain mutant control, single lab","pmids":["17154547"],"is_preprint":false},{"year":2006,"finding":"During embryogenesis, HMGN1 binds to Sox9 chromatin (by ChIP) in cells poised to express Sox9; loss of HMGN1 accelerates chondrocyte differentiation and suppresses Sox9 expression, effects reversible by WT but not chromatin-binding-deficient HMGN1. Loss of HMGN1 increases HMGN2 binding to Sox9 chromatin, suggesting functional redundancy.","method":"Hmgn1-/- limb bud micromass cultures, ChIP assay, mutant rescue, gene expression analysis","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — KO model with chromatin occupancy (ChIP), domain-mutant rescue, and functional differentiation assay, single lab with multiple orthogonal methods","pmids":["16382150"],"is_preprint":false},{"year":2007,"finding":"HMGN1 interacts specifically with estrogen receptor alpha (ERalpha) both in vitro and in vivo; at the TFF1 promoter, estrogen increases HMGN1 association via ERalpha recruitment. HMGN1 also interacts with SRF at the FOS promoter. HMGN1 inhibits estrogen-driven transcriptional activation of TFF1 and FOS, correlating with decreased H3K9 acetylation.","method":"Co-immunoprecipitation, in vitro binding assay, ChIP, knockdown and overexpression, histone modification analysis","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP in vitro and in vivo, ChIP, domain-specific mutant (S20E/S24E), multiple target genes, single lab","pmids":["17938209"],"is_preprint":false},{"year":2008,"finding":"HMGN1 enhances the rate of heat shock-induced H3K14 acetylation at the Hsp70 promoter, accelerating chromatin remodeling and early transcription of Hsp70; HDAC inhibitors abrogate this effect. HMGN1 does not affect basal Hsp70 chromatin structure before induction.","method":"Hmgn1-/- vs. +/+ MEFs, RT-PCR, ChIP for H3K14ac at Hsp70, HDAC inhibitor treatment","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO cell comparison with ChIP and pharmacological inhibitor, single lab, two orthogonal methods","pmids":["18218636"],"is_preprint":false},{"year":2010,"finding":"Genome-wide profiling (ChIP-seq) shows that HMGN1 preferentially localizes to DNase I hypersensitive sites, promoters, functional enhancers, and transcription factor binding sites rather than being randomly distributed throughout chromatin.","method":"ChIP-seq, DNase I hypersensitivity mapping, comparison to regulatory chromatin marks","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genome-wide ChIP-seq with orthogonal validation against multiple chromatin marks, single lab","pmids":["21173166"],"is_preprint":false},{"year":2011,"finding":"HMGN1 is a negative regulator of MeCP2 expression; altered HMGN1 levels change chromatin structure and histone modifications at the MeCP2 promoter. Mice with altered HMGN1 levels show abnormal behavior (activity, anxiety, social deficits).","method":"Hmgn1 overexpressing and KO mouse brain tissue and cell lines, qPCR, western blot, ChIP, behavioral tests","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO and overexpression models, ChIP, multiple behavioral readouts; single lab","pmids":["22009741"],"is_preprint":false},{"year":2012,"finding":"HMGN1 interacts directly with PARP-1 and stimulates PARP-1 self-PARylation; in Hmgn1-/- cells, PARP-1 self-PARylation is reduced in untreated and MMS-treated conditions, and recruitment of PAR to laser-induced DNA damage sites is decreased.","method":"Protein binding assays (Co-IP), in vitro PARylation assay with purified HMGN1 and PARP-1, cell extracts from KO vs. WT mice, live-cell imaging of DNA damage","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstituted PARylation assay with purified proteins + KO cells + live imaging, multiple orthogonal methods, single lab","pmids":["22736760"],"is_preprint":false},{"year":2012,"finding":"HMGN1 interacts with PCNA via two tetrapeptides in its conserved domain; this interaction enhances PCNA binding to chromatin (but not to purified DNA). Loss of HMGN1 decreases the rate of PCNA recruitment to damaged DNA. PCNA preferentially binds linker DNA adjacent to HMGN-containing nucleosomes.","method":"Co-IP/pulldown, deletion mutagenesis, chromatin binding assays, live-cell imaging (PCNA recruitment to laser damage sites) in Hmgn1-/- vs. +/+ cells","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct binding with deletion mutants, functional KO cells, live-cell imaging, multiple orthogonal methods, single lab","pmids":["22393258"],"is_preprint":false},{"year":2013,"finding":"HMGN1 preferentially binds CpG island-containing promoters genome-wide; loss of HMGN1 alters nucleosome organization at transcription start sites (unstable nucleosome), reduces DNase I hypersensitive sites genome-wide, and changes the transcriptional profile in embryonic stem cells and neural progenitors.","method":"MNase-seq, DNase-seq, RNA-seq in Hmgn1-/- vs. +/+ ESCs and neural progenitors, neurosphere assays","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple genome-wide sequencing approaches plus in vivo neural progenitor phenotype, single lab with multiple orthogonal methods","pmids":["23775126"],"is_preprint":false},{"year":2014,"finding":"HMGN1 overexpression (from chromosome 21q22 triplication) suppresses H3K27 trimethylation in progenitor B cells, preferentially derepresses bivalent genes, promotes B cell proliferation in vitro and B-ALL in vivo.","method":"Mouse trisomy models, HMGN1 overexpression constructs, ChIP-seq for H3K27me3, bone marrow transplantation/leukemia in vivo models","journal":"Nature genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo leukemia model, overexpression, ChIP-seq, multiple orthogonal methods, independent validation in human B-ALL","pmids":["24747640"],"is_preprint":false},{"year":2017,"finding":"HMGN1 and HMGN2 counteract linker histone H1-dependent stabilization of higher-order chromatin structures but do not displace H1 from nucleosomes; instead they co-occupy nucleosomes with H1 and alter condensation of the H1 C-terminal domain. HMGNs also redirect core histone tails to more interior nucleosome positions.","method":"Salt-induced compaction and self-association assays, H1 displacement assays, hydroxyl radical footprinting, analytical ultracentrifugation","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Moderate — multiple in vitro biochemical methods (footprinting, compaction assays, sedimentation), single lab, rigorous controls","pmids":["28973435"],"is_preprint":false},{"year":2018,"finding":"Overexpression of HMGN1 recapitulates global transcriptional amplification and a global increase in H3K27 acetylation seen with trisomy of a Down syndrome critical region; HMGN1 is necessary for B cell phenotypes in DS models (spike-in normalized ChIP-Rx and RNA-seq).","method":"Absolute exogenous spike-in normalized ChIP-Rx (H3K27ac) and RNA-seq in DS trisomy and HMGN1-overexpression models","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — absolute-normalized genome-wide ChIP and RNA-seq, HMGN1 overexpression and KO comparisons, replicated across DS models","pmids":["30428356"],"is_preprint":false},{"year":2018,"finding":"Extracellular HMGN1 acts as a TLR4 agonist and promotes dendritic cell recruitment through a Gαi protein-coupled receptor; it preferentially drives Th1-type immunity.","method":"TLR4 binding/signaling assays, DC recruitment assays, DC maturation assays","journal":"Seminars in immunology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — review citing prior experimental findings (TLR4 binding), single lab series, moderate evidence quality","pmids":["29503123"],"is_preprint":false},{"year":2020,"finding":"Knockout or knockdown of HMGN1, alone or combined with HMGN2, does not render human cells sensitive to UV or Illudin S, does not impair transcription restart after UV, and GFP-HMGN1 is not recruited to UV-induced DNA damage sites; HMGN1 does not associate with the TCR complex. These are negative results indicating HMGN1 is NOT required for human transcription-coupled DNA repair.","method":"HMGN1/2 KO and knockdown human cells, UV and Illudin S sensitivity assays, transcription restart assay, live-cell GFP recruitment imaging, co-IP with TCR complex","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal negative results (KO, knockdown, imaging, co-IP), rigorous controls with TCR-deficient cells, single lab","pmids":["32152397"],"is_preprint":false},{"year":2021,"finding":"Phosphorylation of serine residues in the nucleosome-binding domain of HMGN1 induces local conformational changes (decreased helical propensity) and long-range conformational perturbations up to 50–60 residues distant; PTMs had only minor effects on binding to nucleosome core particles in vitro, suggesting other regulatory roles.","method":"NMR spectroscopy, circular dichroism, protein semi-synthesis for site-specific PTMs, segmental isotope labeling, nucleosome binding assays","journal":"RSC chemical biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — NMR + CD + semi-synthesis for site-specific PTMs + binding assays, single lab, multiple orthogonal structural and functional methods","pmids":["34458797"],"is_preprint":false},{"year":2023,"finding":"HMGN1 binds to HBV cccDNA in hepatocyte nuclei (ChIP and FISH); its nucleosomal binding domain is required for this interaction. HMGN1 promotes HBV transcription and replication by reducing phosphorylation of histone H3 (via CLK2), maintaining cccDNA accessibility.","method":"ChIP, FISH, functional HMGN1 mutant analysis, CLK2/H3 phosphorylation measurement, in vivo mouse HBV model","journal":"Antiviral research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP + FISH + domain mutant + in vivo model, single lab, multiple methods","pmids":["38181856"],"is_preprint":false},{"year":2024,"finding":"Phosphorylation of the HMGN1 nucleosome-binding domain decreases helical propensity and disrupts interactions with the nucleosome acidic patch, as shown by NMR spectroscopy and CD; AlphaFold3 modeling corroborates disruption of the HMGN1–acidic patch interface.","method":"NMR spectroscopy, circular dichroism, AlphaFold3 complex modeling","journal":"Chembiochem","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — NMR + CD with site-specific phospho-peptides, single lab, no in-cell validation","pmids":["39186607"],"is_preprint":false},{"year":2025,"finding":"HMGN1 upregulation in trisomy 21 shifts AVC cardiomyocytes toward a ventricular cardiomyocyte transcriptional state; deletion of one HMGN1 allele in trisomic cells or Hmgn1 dosage reduction in a trisomy 21 mouse model restores normal AVC gene expression and rescues valvuloseptal cardiac defects.","method":"Human iPSC cardiac differentiation, CRISPR-activation CROP-seq screen of chr21 genes, single-cell RNA-seq, Hmgn1 allele deletion in trisomy 21 mouse","journal":"Nature","confidence":"High","confidence_rationale":"Tier 2 / Strong — unbiased CROP-seq screen identifies HMGN1, isogenic allele deletion rescues phenotype both in iPSC and mouse model, scRNA-seq, replicated in two model systems","pmids":["41125893"],"is_preprint":false},{"year":2025,"finding":"HMGN1 and HMGN2 preferentially bind nucleosomes with acetylated H3 tail residues and those containing the histone variant H2A.Z; HMGN1/2 binding to nucleosomes reduces p300-mediated acetylation of H3K18, H3K23, and H3K27. In HMGN1/2 double-KO ESCs, H3K27me2 and H3K27me3 are increased without changes in H3 tail acetylation. Loss of both HMGNs downregulates ~1000 genes including cell identity genes.","method":"Engineered Hmgn1-/-, Hmgn2-/-, and Hmgn1-/-Hmgn2-/- mESCs, nucleosome binding assays (modified nucleosomes), in vitro acetylation assays with p300, epiproteomic MS, RNA-seq","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — reconstituted in vitro binding and acetyltransferase assays with modified nucleosomes + isogenic KO cell series + epiproteomic MS + RNA-seq, multiple orthogonal methods","pmids":["41325801"],"is_preprint":false},{"year":2025,"finding":"HMGN1 and HMGN2 function primarily in activation of transcription initiation at over a thousand specific promoters and enhancers; HMGN1 and HMGN2 have both shared and unique transcriptional targets, identified in an HMGN-null human cell line with isogenic rescue lines.","method":"HMGN null human cell line generation, isogenic HMGN1/HMGN2 rescue lines, genome-wide transcriptomic analysis, promoter/enhancer mapping","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — HMGN null cell line with isogenic rescue, genome-wide, preprint not yet peer-reviewed","pmids":["bio_10.1101_2025.11.27.690916"],"is_preprint":true}],"current_model":"HMGN1 is a vertebrate-specific nucleosome-binding protein (binding at the H2A-H2B acidic patch, with domain-specific contacts to H2B via its N-terminus and to H3 N-terminal tails via its C-terminal chromatin-unfolding domain) that preferentially localizes to active regulatory regions (promoters, enhancers, DNase I hypersensitive sites); it reduces higher-order chromatin compaction by counteracting H1-mediated condensation, thereby modulating the accessibility of nucleosomal substrates to kinases (MSK1/2-mediated H3-S10ph, Rsk2/Msk1-mediated H2A-S1ph), acetyltransferases (PCAF-mediated H3K14ac, p300-mediated acetylation of HMGN1 itself), and repair/replication factors (PARP-1 PARylation, PCNA chromatin binding); it is phosphorylated in its nucleosomal binding domain during mitosis (by stress kinases) and upon stress stimulation, triggering interaction with 14-3-3 proteins that prevents nuclear re-entry and weakens chromatin association, providing a cell-cycle regulatory switch; it also interacts with sequence-specific transcription factors (ERα, SRF) to regulate target gene subsets; collectively, HMGN1 functions as a chromatin architectural modulator that globally amplifies transcription initiation and maintains active chromatin states by antagonizing PRC2-mediated H3K27 methylation, with dosage-sensitive effects relevant to Down syndrome-associated B-ALL and congenital heart defects."},"narrative":{"mechanistic_narrative":"HMGN1 is a nucleosome-binding chromatin architectural protein that maintains active chromatin states and amplifies transcription by modulating the accessibility of nucleosomal substrates to chromatin-modifying and DNA-templated machineries [PMID:6449690, PMID:8047885, PMID:bio_10.1101_2025.11.27.690916]. It binds nucleosome core particles cooperatively with two molecules per core, contacting both core DNA near the nucleosome ends and the histones; site-specific photocrosslinking maps its N-terminal nucleosomal binding domain to histone H2B and its acidic C-terminal chromatin-unfolding domain to the H3 N-terminal tail [PMID:6449690, PMID:7971283, PMID:9576905], and phosphorylation of the binding domain disrupts engagement of the nucleosome acidic patch [PMID:39186607]. Functionally, HMGN1 counteracts linker histone H1-dependent higher-order compaction without displacing H1, co-occupying nucleosomes and reducing condensation to keep chromatin open [PMID:28973435], and genome-wide it localizes preferentially to DNase I hypersensitive sites, CpG-island promoters, and enhancers, where its loss destabilizes nucleosomes at transcription start sites and reduces chromatin accessibility [PMID:21173166, PMID:23775126]. Through this open-chromatin function HMGN1 tunes the action of nucleosome-acting enzymes: it enhances PCAF-mediated H3K14 acetylation [PMID:16096646], restrains stress-kinase phosphorylation of nucleosomal H3-S10 and H2A-S1 [PMID:15327773, PMID:17154547], and is itself acetylated by p300 within its binding domain, which weakens nucleosome interaction [PMID:10753971]. HMGN1 also engages DNA-repair and replication factors, binding PARP-1 to stimulate its self-PARylation and binding PCNA to promote its chromatin association [PMID:22736760, PMID:22393258], and interacts with sequence-specific transcription factors ERα and SRF to regulate target gene subsets [PMID:17938209]. Mitotic and stress-induced phosphorylation of the nucleosomal binding domain by MSK1/MSK2 triggers 14-3-3 binding that blocks nuclear re-entry and weakens chromatin association, providing a cell-cycle regulatory switch [PMID:7925294, PMID:12215538, PMID:12773393]. HMGN1 dosage is biologically critical: its overexpression from chromosome 21q22 triplication suppresses PRC2-mediated H3K27 trimethylation, derepresses bivalent genes and drives B-cell proliferation and B-ALL, raises global H3K27 acetylation and transcription, and shifts cardiomyocyte identity to produce valvuloseptal heart defects that are rescued by reducing Hmgn1 dosage [PMID:24747640, PMID:30428356, PMID:41125893]. HMGN1 is not required for human transcription-coupled DNA repair [PMID:32152397].","teleology":[{"year":1980,"claim":"Established that HMGN1 is a dedicated nucleosome-binding protein rather than a generic DNA-binding factor, defining the substrate it acts upon.","evidence":"Thermal denaturation, nuclease digestion, and nucleosome binding assays on chicken erythrocyte chromatin showing two molecules per core with preference for cores over free DNA and enrichment in active gene sequences","pmids":["6449690"],"confidence":"High","gaps":["Did not resolve which histones or DNA regions are contacted","Did not establish a functional consequence of binding"]},{"year":1994,"claim":"Mapped the structural footprint and cooperative binding determinants, and demonstrated that HMGN1's transcriptional effect is strictly nucleosome-dependent.","evidence":"Hydroxyl radical footprinting on nucleosome cores, site-directed mutagenesis (A21P, K26C) of the binding domain, and in vitro Pol II transcription on chromatin vs naked DNA templates","pmids":["8107104","8047885","7971283"],"confidence":"High","gaps":["Did not identify which enzymes the open chromatin affects in vivo","Domain-specific histone contacts not yet resolved"]},{"year":1997,"claim":"Localized the chromatin-unfolding activity to the acidic C-terminal domain and showed it relieves H1-mediated repression, defining the mechanism of transcriptional enhancement.","evidence":"SV40 minichromosome transcription and compaction assays with domain-swap constructs (substitutable by GAL4 or HMG-2 acidic regions)","pmids":["9315642"],"confidence":"High","gaps":["Whether H1 is displaced or co-bound was not resolved until later","In vivo relevance of minichromosome findings untested"]},{"year":1998,"claim":"Resolved domain-specific histone contacts and defined cell-cycle regulation of HMGN1 nuclear localization.","evidence":"Protein photocrosslinking mapping C-terminal domain to H3 tail and N-terminal domain to H2B; immunofluorescence and reconstituted nuclear import assays showing importin-alpha/NLS-dependent late-telophase re-import","pmids":["9576905","9852141"],"confidence":"High","gaps":["Trigger controlling mitotic chromatin release not yet identified","Functional purpose of cell-cycle exclusion unclear"]},{"year":2002,"claim":"Defined how mitotic phosphorylation of the binding domain controls HMGN1 localization, identifying a phospho-dependent 14-3-3 switch.","evidence":"Immunofluorescence, in vitro nuclear import with WT/mutant microinjected proteins, and affinity chromatography with mitotic extracts in Hmgn1-/- background","pmids":["12215538"],"confidence":"High","gaps":["Kinase responsible for mitotic phosphorylation not identified here","Functional 14-3-3 isoform specificity in vivo unresolved"]},{"year":2003,"claim":"Identified MSK1/MSK2 as the kinases for mitogen/stress-induced HMGN1 phosphorylation and established HMGN1 as a chromatin-relaxation factor enhancing nucleotide excision repair.","evidence":"MSK1/MSK2 double-knockout mice abolishing HMGN1 phosphorylation; Hmgn1-/- MEF UV survival, photoproduct removal, host-cell reactivation, and nuclease accessibility with domain-mutant rescue","pmids":["12773393","12660172"],"confidence":"High","gaps":["NER role later contradicted in human cells","How accessibility increase recruits NER factors mechanistically not detailed"]},{"year":2000,"claim":"Showed HMGN1 is itself a substrate of p300 acetylation, with acetylation of the binding domain weakening nucleosome interaction — a layer of self-regulation.","evidence":"In vitro p300 acetyltransferase assays, MS site mapping (7 sites), nucleosome binding assays with acetylated protein, in vivo acetylation analysis","pmids":["10753971"],"confidence":"High","gaps":["In vivo stoichiometry and dynamics of HMGN1 acetylation unknown","Crosstalk with phosphorylation not addressed"]},{"year":2004,"claim":"Established that HMGN1 gates kinase and acetyltransferase access specifically to nucleosomal histones, modulating H3-S10ph, H2A-S1ph and H3K14ac in cells.","evidence":"In vitro kinase/HAT assays on nucleosomal vs free histones (MSK, Rsk2/Msk1, PCAF), Hmgn1-/- cell western analysis, and chromatin-binding-mutant rescue","pmids":["15327773","16096646","17154547"],"confidence":"High","gaps":["Whether modulation is steric or via altered tail positioning not resolved here","Net transcriptional outcome of opposing PTM effects unclear"]},{"year":2005,"claim":"Linked HMGN1 to gene-specific regulation, genome stability, and tumor suppression through in vivo loss-of-function phenotypes.","evidence":"Hmgn1-/- MEFs (N-cadherin/adhesion), Hmgn1-/- mice (ionizing radiation sensitivity, G2-M checkpoint, tumor incidence), DNA microarray, with domain-mutant rescue","pmids":["16279949","16061652"],"confidence":"High","gaps":["Direct chromatin targets driving phenotypes incompletely defined","N-cadherin regulation evidence Medium-confidence"]},{"year":2006,"claim":"Demonstrated developmental chromatin occupancy and functional redundancy with HMGN2 at lineage-control loci.","evidence":"Hmgn1-/- limb-bud micromass cultures, ChIP at Sox9 chromatin, gene expression, and chromatin-binding-mutant rescue with HMGN2 compensation","pmids":["16382150"],"confidence":"High","gaps":["Mechanism of HMGN1-vs-HMGN2 target selection unknown","Direct vs indirect Sox9 regulation not fully separated"]},{"year":2007,"claim":"Connected HMGN1 to sequence-specific transcription factors, showing recruitment via ERα and SRF to regulate defined target genes.","evidence":"Reciprocal Co-IP in vitro and in vivo, ChIP at TFF1 and FOS promoters, knockdown/overexpression, and histone acetylation analysis","pmids":["17938209"],"confidence":"High","gaps":["Generality of TF-mediated recruitment across the genome not established","Direct vs nucleosome-mediated TF contact unresolved"]},{"year":2008,"claim":"Showed HMGN1 accelerates inducible gene activation by promoting H3K14ac at a stress-response promoter.","evidence":"Hmgn1-/- vs +/+ MEFs, RT-PCR, ChIP for H3K14ac at Hsp70, and HDAC inhibitor treatment","pmids":["18218636"],"confidence":"Medium","gaps":["Single-promoter focus","Whether HMGN1 recruits or merely enables the HAT not distinguished"]},{"year":2012,"claim":"Established direct physical and functional coupling of HMGN1 to the DNA-damage and replication factors PARP-1 and PCNA.","evidence":"Co-IP and in vitro reconstituted PARylation with purified proteins; PCNA pulldown/deletion mapping, chromatin-binding assays, and live-cell imaging of recruitment to laser damage in Hmgn1-/- cells","pmids":["22736760","22393258"],"confidence":"High","gaps":["Whether these interactions are direct on chromatin in vivo not fully resolved","Functional consequence for repair outcome in human cells later questioned"]},{"year":2010,"claim":"Defined the genome-wide distribution of HMGN1, showing nonrandom enrichment at active regulatory elements.","evidence":"ChIP-seq with DNase I hypersensitivity mapping and comparison to regulatory chromatin marks","pmids":["21173166"],"confidence":"High","gaps":["Did not establish whether HMGN1 creates or reads accessibility","Sequence determinants of binding not defined"]},{"year":2013,"claim":"Showed HMGN1 shapes chromatin accessibility and the transcriptome at CpG-island promoters in stem and progenitor cells.","evidence":"MNase-seq, DNase-seq, and RNA-seq in Hmgn1-/- vs +/+ ESCs and neural progenitors, with neurosphere assays","pmids":["23775126"],"confidence":"High","gaps":["Causal chain from nucleosome destabilization to transcription change incomplete","Contribution of HMGN2 redundancy not fully separated"]},{"year":2014,"claim":"Established HMGN1 as a dosage-sensitive oncogenic driver in Down syndrome-associated leukemia via PRC2 antagonism.","evidence":"Mouse trisomy and HMGN1-overexpression models, ChIP-seq for H3K27me3, bone-marrow transplant leukemia models, with human B-ALL validation","pmids":["24747640"],"confidence":"High","gaps":["Direct mechanism of H3K27me3 suppression by HMGN1 not biochemically defined here","Whether effect is restricted to B-cell context unclear"]},{"year":2017,"claim":"Resolved the long-standing question of how HMGN1 antagonizes H1 — by co-occupancy and altered condensation rather than displacement.","evidence":"Salt-induced compaction/self-association assays, H1 displacement assays, hydroxyl radical footprinting, and analytical ultracentrifugation","pmids":["28973435"],"confidence":"High","gaps":["In vivo relevance of co-occupancy not directly tested","How altered tail positions translate to enzyme accessibility unresolved"]},{"year":2018,"claim":"Showed HMGN1 overexpression globally amplifies transcription and raises H3K27 acetylation, and is necessary for Down syndrome B-cell phenotypes.","evidence":"Absolute spike-in normalized ChIP-Rx (H3K27ac) and RNA-seq across DS trisomy and HMGN1-overexpression/KO models","pmids":["30428356"],"confidence":"High","gaps":["Mechanism linking HMGN1 dosage to global H3K27ac increase not defined","Causal direction between acetylation and transcription amplification unresolved"]},{"year":2020,"claim":"Refuted the requirement for HMGN1 in human transcription-coupled DNA repair, qualifying the earlier mouse NER role.","evidence":"HMGN1/2 KO and knockdown human cells, UV and Illudin S sensitivity, transcription restart, GFP-HMGN1 damage recruitment imaging, and TCR-complex Co-IP","pmids":["32152397"],"confidence":"High","gaps":["Species/context differences from earlier mouse NER findings not reconciled","Does not exclude repair roles outside the TCR pathway"]},{"year":2021,"claim":"Characterized how phosphorylation reshapes the disordered binding domain, showing local and long-range conformational effects with only minor in vitro binding changes.","evidence":"NMR, CD, protein semi-synthesis with site-specific PTMs, segmental isotope labeling, and nucleosome binding assays","pmids":["34458797"],"confidence":"High","gaps":["Functional readout of conformational changes beyond binding unknown","In-cell consequence of long-range perturbation untested"]},{"year":2023,"claim":"Extended HMGN1's open-chromatin function to viral episomes, showing it maintains HBV cccDNA accessibility by limiting H3 phosphorylation.","evidence":"ChIP, FISH, HMGN1 domain-mutant analysis, CLK2/H3 phosphorylation measurement, and in vivo mouse HBV model","pmids":["38181856"],"confidence":"Medium","gaps":["Single-system viral finding","Direct vs indirect effect on CLK2 not resolved"]},{"year":2024,"claim":"Provided structural-level mechanism for phospho-regulation, showing binding-domain phosphorylation disrupts the HMGN1-acidic patch interface.","evidence":"NMR, CD with site-specific phospho-peptides, and AlphaFold3 complex modeling","pmids":["39186607"],"confidence":"Medium","gaps":["No in-cell validation of acidic-patch disruption","Quantitative affinity change not measured"]},{"year":2025,"claim":"Defined the modification preference and PRC2-antagonizing biochemistry of HMGN1, and established its dosage role in cardiac development.","evidence":"Isogenic Hmgn1/Hmgn2 KO mESCs with modified-nucleosome binding and p300 assays, epiproteomic MS and RNA-seq; iPSC cardiac differentiation, CROP-seq screen, and Hmgn1 allele deletion in trisomy 21 mice rescuing valvuloseptal defects","pmids":["41325801","41125893","30428356"],"confidence":"High","gaps":["How preferential binding to acetylated/H2A.Z nucleosomes is achieved structurally not fully defined","Mechanism connecting reduced p300 acetylation to increased H3K27 methylation unresolved"]},{"year":null,"claim":"It remains unresolved how HMGN1 selects shared versus unique genomic targets relative to HMGN2 and how its dosage is quantitatively translated into global transcriptional amplification and tissue-specific developmental outcomes.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Target-selection determinants between HMGN1 and HMGN2 undefined","Quantitative dose-response relationship linking HMGN1 levels to global transcription and PRC2 antagonism not established","Structural basis for preferential binding to specific modified nucleosomes incomplete"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[1,2]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[3,9]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,7,29]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[5,38]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[15,16,25,37]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[21,26]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[10,12]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[0,23,27]},{"term_id":"GO:0005654","term_label":"nucleoplasm","supporting_discovery_ids":[23,27]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[16,29,37]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[5,27,38]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[10,12,18]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[28,36]}],"complexes":[],"partners":["HMGN2","PARP1","PCNA","EP300","ESR1","SRF","MSK1","PCAF"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P05114","full_name":"Non-histone chromosomal protein HMG-14","aliases":["High mobility group nucleosome-binding domain-containing protein 1"],"length_aa":100,"mass_kda":10.7,"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. Inhibits the phosphorylation of nucleosomal histones H3 and H2A by RPS6KA5/MSK1 and RPS6KA3/RSK2 (By similarity)","subcellular_location":"Nucleus; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/P05114/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/HMGN1","classification":"Not Classified","n_dependent_lines":144,"n_total_lines":1090,"dependency_fraction":0.13211009174311927},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/HMGN1","total_profiled":1310},"omim":[{"mim_id":"605036","title":"ZINC FINGER PROTEIN 219; ZNF219","url":"https://www.omim.org/entry/605036"},{"mim_id":"604502","title":"HIGH MOBILITY GROUP NUCLEOSOMAL BINDING PROTEIN 3; HMGN3","url":"https://www.omim.org/entry/604502"},{"mim_id":"602915","title":"GUIDED ENTRY OF TAIL-ANCHORED PROTEINS FACTOR 1; GET1","url":"https://www.omim.org/entry/602915"},{"mim_id":"190685","title":"DOWN SYNDROME","url":"https://www.omim.org/entry/190685"},{"mim_id":"163920","title":"HIGH MOBILITY GROUP NUCLEOSOMAL BINDING PROTEIN 1; HMGN1","url":"https://www.omim.org/entry/163920"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/HMGN1"},"hgnc":{"alias_symbol":["FLJ27265","FLJ31471","MGC104230","MGC117425"],"prev_symbol":["HMG14"]},"alphafold":{"accession":"P05114","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P05114","model_url":"https://alphafold.ebi.ac.uk/files/AF-P05114-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P05114-F1-predicted_aligned_error_v6.png","plddt_mean":63.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=HMGN1","jax_strain_url":"https://www.jax.org/strain/search?query=HMGN1"},"sequence":{"accession":"P05114","fasta_url":"https://rest.uniprot.org/uniprotkb/P05114.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P05114/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P05114"}},"corpus_meta":[{"pmid":"12773393","id":"PMC_12773393","title":"MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and 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Nucleosome-HMG complexes are enriched in transcriptionally active gene sequences.\",\n      \"method\": \"Thermal denaturation, nuclease digestion, nucleosome binding assays with chicken erythrocyte chromatin\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — multiple orthogonal biochemical methods (thermal denaturation, nuclease digestion, DNA sequence enrichment), replicated across multiple labs in this era\",\n      \"pmids\": [\"6449690\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1980,\n      \"finding\": \"HMG-14 is intrinsically disordered in free solution (assessed by NMR and CD), binds DNA via its N-terminal half at low ionic strength, and is released at 0.3 M NaCl (matching chromatin extraction conditions).\",\n      \"method\": \"270-MHz NMR, circular dichroism\",\n      \"journal\": \"European journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — NMR and CD in single study, no functional mutagenesis validation\",\n      \"pmids\": [\"6257511\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1981,\n      \"finding\": \"HMGN1 (HMG-14) preferentially binds single-stranded DNA over double-stranded DNA, as demonstrated by sequential affinity chromatography.\",\n      \"method\": \"Sequential affinity chromatography on immobilized ss- and ds-DNA columns with purified protein\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct biochemical binding assay with purified protein, single lab, single method\",\n      \"pmids\": [\"7279673\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1985,\n      \"finding\": \"HMGN1 (HMG-14) contacts histones H2A, H2B, and H1, as well as DNA, within nucleosomes, as identified by chemical crosslinking with photoactivable heterobifunctional reagents in reconstituted chromatin.\",\n      \"method\": \"Reconstitution and chemical crosslinking with photoactivable reagents in chromatin\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct crosslinking in reconstituted chromatin, single lab, single method\",\n      \"pmids\": [\"4074344\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"HMGN1 (HMG-14) maps the footprint on nucleosome cores at two positions: 25 bp from the end of core DNA and in each of the two major grooves flanking the dyad axis, bridging two adjacent DNA strands. The chromatin footprint of HMG-14 is indistinguishable from HMG-17.\",\n      \"method\": \"Hydroxyl radical footprinting of HMG-14/-17 on nucleosome cores and chromatosomes\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — hydroxyl radical footprinting (high-resolution structural method) with both H1-containing and H1-depleted particles, single lab but multiple particle types\",\n      \"pmids\": [\"8107104\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"HMGN1 (HMG-14) stimulates the rate of RNA polymerase II elongation on chromatin templates but not on naked DNA, establishing that its effect on transcription is nucleosome-dependent.\",\n      \"method\": \"In vitro transcription assays on in vivo-assembled chromatin templates vs. DNA templates\",\n      \"journal\": \"Science (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — reconstituted in vitro transcription assay on chromatin vs. DNA, directly tests mechanism, single lab with clear positive and negative controls\",\n      \"pmids\": [\"8047885\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"Upon mitogenic or stress stimulation, HMG-14 (HMGN1) is phosphorylated in its basic N-terminal domain on mononucleosome-associated protein by a mitogen-activated kinase; the phosphorylation is transient, quantitative, and occurs independently of transcription.\",\n      \"method\": \"In vivo phosphorylation mapping, micrococcal nuclease fractionation, in vitro kinase assay on isolated mononucleosomes\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro kinase assay on isolated mononucleosomes plus in vivo site mapping, single lab, multiple orthogonal approaches\",\n      \"pmids\": [\"7925294\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"Single point mutations in the nucleosomal binding domain of HMGN1 (A21P or K26C) reduce cooperative binding to nucleosome cores 6.7- and 3-fold respectively, while non-cooperative binding is minimally affected, indicating a conformational change upon cooperative binding.\",\n      \"method\": \"Site-directed mutagenesis + nucleosome core binding assays\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct mutagenesis with quantitative binding assay, multiple mutants tested, single lab\",\n      \"pmids\": [\"7971283\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"The acidic C-terminal region of HMG-14 (HMGN1) is necessary and sufficient to alleviate histone H1-mediated transcriptional repression and partially disrupt H1-dependent chromatin compaction; these activities can be substituted by acidic regions from GAL4 or HMG-2.\",\n      \"method\": \"SV40 minichromosome transcription assays, chromatin compaction assays, domain-swap experiments\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — reconstituted minichromosome system with domain-swap controls, multiple readouts (transcription and chromatin structure), single lab\",\n      \"pmids\": [\"9315642\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"The C-terminal chromatin-unfolding domain of HMG-14 (HMGN1) targets the N-terminal tail of histone H3 in nucleosomes, while the N-terminal domain of HMG-14 targets histone H2B, as demonstrated by protein photocrosslinking.\",\n      \"method\": \"Protein photocrosslinking in nucleosome cores\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct site-specific photocrosslinking mapping domain contacts, single lab, clear structural-functional correlation\",\n      \"pmids\": [\"9576905\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"HMGN1 (HMG-14/-17) proteins are released from chromatin during mitosis (absent in metaphase/anaphase) and actively re-imported into the nucleus in late telophase through a process requiring energy, importin alpha, and the proteins' intrinsic bipartite nuclear localization signal.\",\n      \"method\": \"Immunofluorescence cell cycle analysis, reconstituted nuclei nuclear import assays, permeabilized cell import assays\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct live-cell imaging plus reconstituted nuclear import assays, multiple orthogonal methods, single lab\",\n      \"pmids\": [\"9852141\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"The histone acetyltransferase p300 specifically acetylates HMGN1 (HMG-14) at 7 major sites (6 novel), including 3 within the nucleosomal binding domain and 4 near the bipartite NLS; acetylation of the nucleosomal binding domain weakens HMGN1's interaction with nucleosome cores.\",\n      \"method\": \"In vitro acetyltransferase assays with purified p300, mass spectrometry of acetylation sites, nucleosome binding assays with acetylated protein, in vivo acetylation analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — reconstituted in vitro acetylation with purified p300, site identification by MS, functional binding assay, in vivo validation, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"10753971\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Mitotic phosphorylation of the nucleosomal binding domain (NBD) of HMGN1 prevents nuclear re-entry in late telophase and promotes interaction with specific 14-3-3 isoforms; this inhibition is due to the phosphorylation itself, not merely to the addition of negative charges.\",\n      \"method\": \"Immunofluorescence, in vitro nuclear import assays with microinjected WT and mutant proteins, affinity chromatography with recombinant proteins and mitotic cell extracts\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal protein binding assays, nuclear import reconstitution, mutant rescue in Hmgn1-/- cells, multiple orthogonal methods in single lab\",\n      \"pmids\": [\"12215538\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"MSK1 and MSK2 are the major kinases responsible for mitogen- and stress-induced phosphorylation of HMGN1 (HMG-14) in fibroblasts, as shown by the severe reduction or abolition of HMG-14 phosphorylation in MSK1/MSK2 double-knockout mice.\",\n      \"method\": \"Genetic knockout (MSK1-/-, MSK2-/-, double KO mice), phosphorylation assays in Coffin-Lowry cells and mouse fibroblasts\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic epistasis using double-knockout animals, replicated across multiple cell types and genetic backgrounds\",\n      \"pmids\": [\"12773393\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"HMGN1 enhances the rate of nucleotide excision repair (NER) of UV-induced photoproducts in chromatin by reducing higher-order chromatin compaction and increasing accessibility to damaged DNA; this activity requires both nucleosome binding and chromatin-unfolding functions of HMGN1.\",\n      \"method\": \"Hmgn1-/- MEFs UV sensitivity assay, photoproduct removal kinetics, host cell reactivation, NER pathway analysis, mutant HMGN1 rescue transfections, nuclease accessibility assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — KO cells + domain-specific mutant rescue + multiple orthogonal readouts (UV survival, photoproduct removal, nuclease accessibility), single lab\",\n      \"pmids\": [\"12660172\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"HMGN1 reduces the rate of stress-induced phosphorylation of histone H3 at Ser10 by hindering kinase access to nucleosomal (but not free) H3; in Hmgn1-/- cells, steady-state H3-pS10 levels are elevated. HMGN1 itself is phosphorylated by anisomycin-induced kinases before H3, causing transient weakening of its chromatin binding.\",\n      \"method\": \"In vitro kinase assays on nucleosomal vs. free H3, Hmgn1-/- cell western analysis, in vivo phosphorylation kinetics\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstituted kinase assay on nucleosomes plus in vivo KO validation, multiple orthogonal approaches, single lab\",\n      \"pmids\": [\"15327773\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"HMGN1 elevates H3K14 acetylation by enhancing HAT (PCAF) activity on nucleosomal, but not free, H3; loss of HMGN1 in Hmgn1-/- cells reduces H3K14ac, and wild-type but not chromatin-binding-deficient HMGN1 rescues this.\",\n      \"method\": \"In vitro PCAF acetyltransferase assays on nucleosomes vs. free H3, Hmgn1-/- cell rescue with WT vs. mutant HMGN1, western analysis of H3K14ac\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — reconstituted in vitro acetyltransferase assay on nucleosomes plus in vivo KO rescue with domain-specific mutant, multiple methods, single lab\",\n      \"pmids\": [\"16096646\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"HMGN1 negatively regulates N-cadherin expression in MEFs; loss of HMGN1 increases N-cadherin levels leading to increased cell adhesiveness, motility and aggregation, and this is rescued by WT but not chromatin-binding-deficient HMGN1.\",\n      \"method\": \"Hmgn1-/- MEFs, DNA microarray, RT-PCR, western blot, mutant rescue, cell adhesion/motility assays\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO + rescue with domain-specific mutant, multiple gene expression and functional readouts, single lab\",\n      \"pmids\": [\"16279949\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Loss of HMGN1 increases sensitivity to ionizing radiation, elevates tumor burden, and disrupts G2-M checkpoint activation in fibroblasts; these defects are rescued by WT but not chromatin-binding-deficient HMGN1.\",\n      \"method\": \"Hmgn1-/- mouse model, ionizing radiation survival, tumor incidence, cell cycle checkpoint analysis, mutant rescue transfections\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo KO mouse model plus mechanistic domain-mutant rescue, multiple phenotypic readouts (radiation sensitivity, G2-M checkpoint, tumorigenesis)\",\n      \"pmids\": [\"16061652\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"HMGN1 modulates phosphorylation of histone H2A at Ser1; in Hmgn1-/- cells, H2AS1ph levels are elevated throughout the cell cycle. In vitro, HMGN1 reduces Rsk2- and Msk1-mediated phosphorylation of nucleosomal but not free H2A, requiring HMGN1-chromatin binding.\",\n      \"method\": \"In vitro kinase assays with Rsk2 and Msk1 on nucleosomal vs. free H2A, Hmgn1-/- cell western analysis, chromatin-binding mutant controls\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — reconstituted in vitro kinase assay on nucleosomes plus KO validation, domain mutant control, single lab\",\n      \"pmids\": [\"17154547\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"During embryogenesis, HMGN1 binds to Sox9 chromatin (by ChIP) in cells poised to express Sox9; loss of HMGN1 accelerates chondrocyte differentiation and suppresses Sox9 expression, effects reversible by WT but not chromatin-binding-deficient HMGN1. Loss of HMGN1 increases HMGN2 binding to Sox9 chromatin, suggesting functional redundancy.\",\n      \"method\": \"Hmgn1-/- limb bud micromass cultures, ChIP assay, mutant rescue, gene expression analysis\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — KO model with chromatin occupancy (ChIP), domain-mutant rescue, and functional differentiation assay, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"16382150\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"HMGN1 interacts specifically with estrogen receptor alpha (ERalpha) both in vitro and in vivo; at the TFF1 promoter, estrogen increases HMGN1 association via ERalpha recruitment. HMGN1 also interacts with SRF at the FOS promoter. HMGN1 inhibits estrogen-driven transcriptional activation of TFF1 and FOS, correlating with decreased H3K9 acetylation.\",\n      \"method\": \"Co-immunoprecipitation, in vitro binding assay, ChIP, knockdown and overexpression, histone modification analysis\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP in vitro and in vivo, ChIP, domain-specific mutant (S20E/S24E), multiple target genes, single lab\",\n      \"pmids\": [\"17938209\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"HMGN1 enhances the rate of heat shock-induced H3K14 acetylation at the Hsp70 promoter, accelerating chromatin remodeling and early transcription of Hsp70; HDAC inhibitors abrogate this effect. HMGN1 does not affect basal Hsp70 chromatin structure before induction.\",\n      \"method\": \"Hmgn1-/- vs. +/+ MEFs, RT-PCR, ChIP for H3K14ac at Hsp70, HDAC inhibitor treatment\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO cell comparison with ChIP and pharmacological inhibitor, single lab, two orthogonal methods\",\n      \"pmids\": [\"18218636\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Genome-wide profiling (ChIP-seq) shows that HMGN1 preferentially localizes to DNase I hypersensitive sites, promoters, functional enhancers, and transcription factor binding sites rather than being randomly distributed throughout chromatin.\",\n      \"method\": \"ChIP-seq, DNase I hypersensitivity mapping, comparison to regulatory chromatin marks\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide ChIP-seq with orthogonal validation against multiple chromatin marks, single lab\",\n      \"pmids\": [\"21173166\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"HMGN1 is a negative regulator of MeCP2 expression; altered HMGN1 levels change chromatin structure and histone modifications at the MeCP2 promoter. Mice with altered HMGN1 levels show abnormal behavior (activity, anxiety, social deficits).\",\n      \"method\": \"Hmgn1 overexpressing and KO mouse brain tissue and cell lines, qPCR, western blot, ChIP, behavioral tests\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO and overexpression models, ChIP, multiple behavioral readouts; single lab\",\n      \"pmids\": [\"22009741\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"HMGN1 interacts directly with PARP-1 and stimulates PARP-1 self-PARylation; in Hmgn1-/- cells, PARP-1 self-PARylation is reduced in untreated and MMS-treated conditions, and recruitment of PAR to laser-induced DNA damage sites is decreased.\",\n      \"method\": \"Protein binding assays (Co-IP), in vitro PARylation assay with purified HMGN1 and PARP-1, cell extracts from KO vs. WT mice, live-cell imaging of DNA damage\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstituted PARylation assay with purified proteins + KO cells + live imaging, multiple orthogonal methods, single lab\",\n      \"pmids\": [\"22736760\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"HMGN1 interacts with PCNA via two tetrapeptides in its conserved domain; this interaction enhances PCNA binding to chromatin (but not to purified DNA). Loss of HMGN1 decreases the rate of PCNA recruitment to damaged DNA. PCNA preferentially binds linker DNA adjacent to HMGN-containing nucleosomes.\",\n      \"method\": \"Co-IP/pulldown, deletion mutagenesis, chromatin binding assays, live-cell imaging (PCNA recruitment to laser damage sites) in Hmgn1-/- vs. +/+ cells\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct binding with deletion mutants, functional KO cells, live-cell imaging, multiple orthogonal methods, single lab\",\n      \"pmids\": [\"22393258\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"HMGN1 preferentially binds CpG island-containing promoters genome-wide; loss of HMGN1 alters nucleosome organization at transcription start sites (unstable nucleosome), reduces DNase I hypersensitive sites genome-wide, and changes the transcriptional profile in embryonic stem cells and neural progenitors.\",\n      \"method\": \"MNase-seq, DNase-seq, RNA-seq in Hmgn1-/- vs. +/+ ESCs and neural progenitors, neurosphere assays\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple genome-wide sequencing approaches plus in vivo neural progenitor phenotype, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"23775126\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"HMGN1 overexpression (from chromosome 21q22 triplication) suppresses H3K27 trimethylation in progenitor B cells, preferentially derepresses bivalent genes, promotes B cell proliferation in vitro and B-ALL in vivo.\",\n      \"method\": \"Mouse trisomy models, HMGN1 overexpression constructs, ChIP-seq for H3K27me3, bone marrow transplantation/leukemia in vivo models\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo leukemia model, overexpression, ChIP-seq, multiple orthogonal methods, independent validation in human B-ALL\",\n      \"pmids\": [\"24747640\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"HMGN1 and HMGN2 counteract linker histone H1-dependent stabilization of higher-order chromatin structures but do not displace H1 from nucleosomes; instead they co-occupy nucleosomes with H1 and alter condensation of the H1 C-terminal domain. HMGNs also redirect core histone tails to more interior nucleosome positions.\",\n      \"method\": \"Salt-induced compaction and self-association assays, H1 displacement assays, hydroxyl radical footprinting, analytical ultracentrifugation\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — multiple in vitro biochemical methods (footprinting, compaction assays, sedimentation), single lab, rigorous controls\",\n      \"pmids\": [\"28973435\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Overexpression of HMGN1 recapitulates global transcriptional amplification and a global increase in H3K27 acetylation seen with trisomy of a Down syndrome critical region; HMGN1 is necessary for B cell phenotypes in DS models (spike-in normalized ChIP-Rx and RNA-seq).\",\n      \"method\": \"Absolute exogenous spike-in normalized ChIP-Rx (H3K27ac) and RNA-seq in DS trisomy and HMGN1-overexpression models\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — absolute-normalized genome-wide ChIP and RNA-seq, HMGN1 overexpression and KO comparisons, replicated across DS models\",\n      \"pmids\": [\"30428356\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Extracellular HMGN1 acts as a TLR4 agonist and promotes dendritic cell recruitment through a Gαi protein-coupled receptor; it preferentially drives Th1-type immunity.\",\n      \"method\": \"TLR4 binding/signaling assays, DC recruitment assays, DC maturation assays\",\n      \"journal\": \"Seminars in immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — review citing prior experimental findings (TLR4 binding), single lab series, moderate evidence quality\",\n      \"pmids\": [\"29503123\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Knockout or knockdown of HMGN1, alone or combined with HMGN2, does not render human cells sensitive to UV or Illudin S, does not impair transcription restart after UV, and GFP-HMGN1 is not recruited to UV-induced DNA damage sites; HMGN1 does not associate with the TCR complex. These are negative results indicating HMGN1 is NOT required for human transcription-coupled DNA repair.\",\n      \"method\": \"HMGN1/2 KO and knockdown human cells, UV and Illudin S sensitivity assays, transcription restart assay, live-cell GFP recruitment imaging, co-IP with TCR complex\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal negative results (KO, knockdown, imaging, co-IP), rigorous controls with TCR-deficient cells, single lab\",\n      \"pmids\": [\"32152397\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Phosphorylation of serine residues in the nucleosome-binding domain of HMGN1 induces local conformational changes (decreased helical propensity) and long-range conformational perturbations up to 50–60 residues distant; PTMs had only minor effects on binding to nucleosome core particles in vitro, suggesting other regulatory roles.\",\n      \"method\": \"NMR spectroscopy, circular dichroism, protein semi-synthesis for site-specific PTMs, segmental isotope labeling, nucleosome binding assays\",\n      \"journal\": \"RSC chemical biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — NMR + CD + semi-synthesis for site-specific PTMs + binding assays, single lab, multiple orthogonal structural and functional methods\",\n      \"pmids\": [\"34458797\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"HMGN1 binds to HBV cccDNA in hepatocyte nuclei (ChIP and FISH); its nucleosomal binding domain is required for this interaction. HMGN1 promotes HBV transcription and replication by reducing phosphorylation of histone H3 (via CLK2), maintaining cccDNA accessibility.\",\n      \"method\": \"ChIP, FISH, functional HMGN1 mutant analysis, CLK2/H3 phosphorylation measurement, in vivo mouse HBV model\",\n      \"journal\": \"Antiviral research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP + FISH + domain mutant + in vivo model, single lab, multiple methods\",\n      \"pmids\": [\"38181856\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Phosphorylation of the HMGN1 nucleosome-binding domain decreases helical propensity and disrupts interactions with the nucleosome acidic patch, as shown by NMR spectroscopy and CD; AlphaFold3 modeling corroborates disruption of the HMGN1–acidic patch interface.\",\n      \"method\": \"NMR spectroscopy, circular dichroism, AlphaFold3 complex modeling\",\n      \"journal\": \"Chembiochem\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — NMR + CD with site-specific phospho-peptides, single lab, no in-cell validation\",\n      \"pmids\": [\"39186607\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"HMGN1 upregulation in trisomy 21 shifts AVC cardiomyocytes toward a ventricular cardiomyocyte transcriptional state; deletion of one HMGN1 allele in trisomic cells or Hmgn1 dosage reduction in a trisomy 21 mouse model restores normal AVC gene expression and rescues valvuloseptal cardiac defects.\",\n      \"method\": \"Human iPSC cardiac differentiation, CRISPR-activation CROP-seq screen of chr21 genes, single-cell RNA-seq, Hmgn1 allele deletion in trisomy 21 mouse\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — unbiased CROP-seq screen identifies HMGN1, isogenic allele deletion rescues phenotype both in iPSC and mouse model, scRNA-seq, replicated in two model systems\",\n      \"pmids\": [\"41125893\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"HMGN1 and HMGN2 preferentially bind nucleosomes with acetylated H3 tail residues and those containing the histone variant H2A.Z; HMGN1/2 binding to nucleosomes reduces p300-mediated acetylation of H3K18, H3K23, and H3K27. In HMGN1/2 double-KO ESCs, H3K27me2 and H3K27me3 are increased without changes in H3 tail acetylation. Loss of both HMGNs downregulates ~1000 genes including cell identity genes.\",\n      \"method\": \"Engineered Hmgn1-/-, Hmgn2-/-, and Hmgn1-/-Hmgn2-/- mESCs, nucleosome binding assays (modified nucleosomes), in vitro acetylation assays with p300, epiproteomic MS, RNA-seq\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — reconstituted in vitro binding and acetyltransferase assays with modified nucleosomes + isogenic KO cell series + epiproteomic MS + RNA-seq, multiple orthogonal methods\",\n      \"pmids\": [\"41325801\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"HMGN1 and HMGN2 function primarily in activation of transcription initiation at over a thousand specific promoters and enhancers; HMGN1 and HMGN2 have both shared and unique transcriptional targets, identified in an HMGN-null human cell line with isogenic rescue lines.\",\n      \"method\": \"HMGN null human cell line generation, isogenic HMGN1/HMGN2 rescue lines, genome-wide transcriptomic analysis, promoter/enhancer mapping\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — HMGN null cell line with isogenic rescue, genome-wide, preprint not yet peer-reviewed\",\n      \"pmids\": [\"bio_10.1101_2025.11.27.690916\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"HMGN1 is a vertebrate-specific nucleosome-binding protein (binding at the H2A-H2B acidic patch, with domain-specific contacts to H2B via its N-terminus and to H3 N-terminal tails via its C-terminal chromatin-unfolding domain) that preferentially localizes to active regulatory regions (promoters, enhancers, DNase I hypersensitive sites); it reduces higher-order chromatin compaction by counteracting H1-mediated condensation, thereby modulating the accessibility of nucleosomal substrates to kinases (MSK1/2-mediated H3-S10ph, Rsk2/Msk1-mediated H2A-S1ph), acetyltransferases (PCAF-mediated H3K14ac, p300-mediated acetylation of HMGN1 itself), and repair/replication factors (PARP-1 PARylation, PCNA chromatin binding); it is phosphorylated in its nucleosomal binding domain during mitosis (by stress kinases) and upon stress stimulation, triggering interaction with 14-3-3 proteins that prevents nuclear re-entry and weakens chromatin association, providing a cell-cycle regulatory switch; it also interacts with sequence-specific transcription factors (ERα, SRF) to regulate target gene subsets; collectively, HMGN1 functions as a chromatin architectural modulator that globally amplifies transcription initiation and maintains active chromatin states by antagonizing PRC2-mediated H3K27 methylation, with dosage-sensitive effects relevant to Down syndrome-associated B-ALL and congenital heart defects.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"HMGN1 is a nucleosome-binding chromatin architectural protein that maintains active chromatin states and amplifies transcription by modulating the accessibility of nucleosomal substrates to chromatin-modifying and DNA-templated machineries [#0, #5, #38]. It binds nucleosome core particles cooperatively with two molecules per core, contacting both core DNA near the nucleosome ends and the histones; site-specific photocrosslinking maps its N-terminal nucleosomal binding domain to histone H2B and its acidic C-terminal chromatin-unfolding domain to the H3 N-terminal tail [#0, #7, #9], and phosphorylation of the binding domain disrupts engagement of the nucleosome acidic patch [#35]. Functionally, HMGN1 counteracts linker histone H1-dependent higher-order compaction without displacing H1, co-occupying nucleosomes and reducing condensation to keep chromatin open [#29], and genome-wide it localizes preferentially to DNase I hypersensitive sites, CpG-island promoters, and enhancers, where its loss destabilizes nucleosomes at transcription start sites and reduces chromatin accessibility [#23, #27]. Through this open-chromatin function HMGN1 tunes the action of nucleosome-acting enzymes: it enhances PCAF-mediated H3K14 acetylation [#16], restrains stress-kinase phosphorylation of nucleosomal H3-S10 and H2A-S1 [#15, #19], and is itself acetylated by p300 within its binding domain, which weakens nucleosome interaction [#11]. HMGN1 also engages DNA-repair and replication factors, binding PARP-1 to stimulate its self-PARylation and binding PCNA to promote its chromatin association [#25, #26], and interacts with sequence-specific transcription factors ERα and SRF to regulate target gene subsets [#21]. Mitotic and stress-induced phosphorylation of the nucleosomal binding domain by MSK1/MSK2 triggers 14-3-3 binding that blocks nuclear re-entry and weakens chromatin association, providing a cell-cycle regulatory switch [#6, #12, #13]. HMGN1 dosage is biologically critical: its overexpression from chromosome 21q22 triplication suppresses PRC2-mediated H3K27 trimethylation, derepresses bivalent genes and drives B-cell proliferation and B-ALL, raises global H3K27 acetylation and transcription, and shifts cardiomyocyte identity to produce valvuloseptal heart defects that are rescued by reducing Hmgn1 dosage [#28, #30, #36]. HMGN1 is not required for human transcription-coupled DNA repair [#32].\",\n  \"teleology\": [\n    {\n      \"year\": 1980,\n      \"claim\": \"Established that HMGN1 is a dedicated nucleosome-binding protein rather than a generic DNA-binding factor, defining the substrate it acts upon.\",\n      \"evidence\": \"Thermal denaturation, nuclease digestion, and nucleosome binding assays on chicken erythrocyte chromatin showing two molecules per core with preference for cores over free DNA and enrichment in active gene sequences\",\n      \"pmids\": [\"6449690\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve which histones or DNA regions are contacted\", \"Did not establish a functional consequence of binding\"]\n    },\n    {\n      \"year\": 1994,\n      \"claim\": \"Mapped the structural footprint and cooperative binding determinants, and demonstrated that HMGN1's transcriptional effect is strictly nucleosome-dependent.\",\n      \"evidence\": \"Hydroxyl radical footprinting on nucleosome cores, site-directed mutagenesis (A21P, K26C) of the binding domain, and in vitro Pol II transcription on chromatin vs naked DNA templates\",\n      \"pmids\": [\"8107104\", \"8047885\", \"7971283\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not identify which enzymes the open chromatin affects in vivo\", \"Domain-specific histone contacts not yet resolved\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Localized the chromatin-unfolding activity to the acidic C-terminal domain and showed it relieves H1-mediated repression, defining the mechanism of transcriptional enhancement.\",\n      \"evidence\": \"SV40 minichromosome transcription and compaction assays with domain-swap constructs (substitutable by GAL4 or HMG-2 acidic regions)\",\n      \"pmids\": [\"9315642\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether H1 is displaced or co-bound was not resolved until later\", \"In vivo relevance of minichromosome findings untested\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Resolved domain-specific histone contacts and defined cell-cycle regulation of HMGN1 nuclear localization.\",\n      \"evidence\": \"Protein photocrosslinking mapping C-terminal domain to H3 tail and N-terminal domain to H2B; immunofluorescence and reconstituted nuclear import assays showing importin-alpha/NLS-dependent late-telophase re-import\",\n      \"pmids\": [\"9576905\", \"9852141\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Trigger controlling mitotic chromatin release not yet identified\", \"Functional purpose of cell-cycle exclusion unclear\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Defined how mitotic phosphorylation of the binding domain controls HMGN1 localization, identifying a phospho-dependent 14-3-3 switch.\",\n      \"evidence\": \"Immunofluorescence, in vitro nuclear import with WT/mutant microinjected proteins, and affinity chromatography with mitotic extracts in Hmgn1-/- background\",\n      \"pmids\": [\"12215538\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinase responsible for mitotic phosphorylation not identified here\", \"Functional 14-3-3 isoform specificity in vivo unresolved\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Identified MSK1/MSK2 as the kinases for mitogen/stress-induced HMGN1 phosphorylation and established HMGN1 as a chromatin-relaxation factor enhancing nucleotide excision repair.\",\n      \"evidence\": \"MSK1/MSK2 double-knockout mice abolishing HMGN1 phosphorylation; Hmgn1-/- MEF UV survival, photoproduct removal, host-cell reactivation, and nuclease accessibility with domain-mutant rescue\",\n      \"pmids\": [\"12773393\", \"12660172\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"NER role later contradicted in human cells\", \"How accessibility increase recruits NER factors mechanistically not detailed\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Showed HMGN1 is itself a substrate of p300 acetylation, with acetylation of the binding domain weakening nucleosome interaction — a layer of self-regulation.\",\n      \"evidence\": \"In vitro p300 acetyltransferase assays, MS site mapping (7 sites), nucleosome binding assays with acetylated protein, in vivo acetylation analysis\",\n      \"pmids\": [\"10753971\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo stoichiometry and dynamics of HMGN1 acetylation unknown\", \"Crosstalk with phosphorylation not addressed\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Established that HMGN1 gates kinase and acetyltransferase access specifically to nucleosomal histones, modulating H3-S10ph, H2A-S1ph and H3K14ac in cells.\",\n      \"evidence\": \"In vitro kinase/HAT assays on nucleosomal vs free histones (MSK, Rsk2/Msk1, PCAF), Hmgn1-/- cell western analysis, and chromatin-binding-mutant rescue\",\n      \"pmids\": [\"15327773\", \"16096646\", \"17154547\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether modulation is steric or via altered tail positioning not resolved here\", \"Net transcriptional outcome of opposing PTM effects unclear\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Linked HMGN1 to gene-specific regulation, genome stability, and tumor suppression through in vivo loss-of-function phenotypes.\",\n      \"evidence\": \"Hmgn1-/- MEFs (N-cadherin/adhesion), Hmgn1-/- mice (ionizing radiation sensitivity, G2-M checkpoint, tumor incidence), DNA microarray, with domain-mutant rescue\",\n      \"pmids\": [\"16279949\", \"16061652\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct chromatin targets driving phenotypes incompletely defined\", \"N-cadherin regulation evidence Medium-confidence\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Demonstrated developmental chromatin occupancy and functional redundancy with HMGN2 at lineage-control loci.\",\n      \"evidence\": \"Hmgn1-/- limb-bud micromass cultures, ChIP at Sox9 chromatin, gene expression, and chromatin-binding-mutant rescue with HMGN2 compensation\",\n      \"pmids\": [\"16382150\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of HMGN1-vs-HMGN2 target selection unknown\", \"Direct vs indirect Sox9 regulation not fully separated\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Connected HMGN1 to sequence-specific transcription factors, showing recruitment via ERα and SRF to regulate defined target genes.\",\n      \"evidence\": \"Reciprocal Co-IP in vitro and in vivo, ChIP at TFF1 and FOS promoters, knockdown/overexpression, and histone acetylation analysis\",\n      \"pmids\": [\"17938209\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Generality of TF-mediated recruitment across the genome not established\", \"Direct vs nucleosome-mediated TF contact unresolved\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Showed HMGN1 accelerates inducible gene activation by promoting H3K14ac at a stress-response promoter.\",\n      \"evidence\": \"Hmgn1-/- vs +/+ MEFs, RT-PCR, ChIP for H3K14ac at Hsp70, and HDAC inhibitor treatment\",\n      \"pmids\": [\"18218636\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single-promoter focus\", \"Whether HMGN1 recruits or merely enables the HAT not distinguished\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Established direct physical and functional coupling of HMGN1 to the DNA-damage and replication factors PARP-1 and PCNA.\",\n      \"evidence\": \"Co-IP and in vitro reconstituted PARylation with purified proteins; PCNA pulldown/deletion mapping, chromatin-binding assays, and live-cell imaging of recruitment to laser damage in Hmgn1-/- cells\",\n      \"pmids\": [\"22736760\", \"22393258\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether these interactions are direct on chromatin in vivo not fully resolved\", \"Functional consequence for repair outcome in human cells later questioned\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Defined the genome-wide distribution of HMGN1, showing nonrandom enrichment at active regulatory elements.\",\n      \"evidence\": \"ChIP-seq with DNase I hypersensitivity mapping and comparison to regulatory chromatin marks\",\n      \"pmids\": [\"21173166\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not establish whether HMGN1 creates or reads accessibility\", \"Sequence determinants of binding not defined\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Showed HMGN1 shapes chromatin accessibility and the transcriptome at CpG-island promoters in stem and progenitor cells.\",\n      \"evidence\": \"MNase-seq, DNase-seq, and RNA-seq in Hmgn1-/- vs +/+ ESCs and neural progenitors, with neurosphere assays\",\n      \"pmids\": [\"23775126\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Causal chain from nucleosome destabilization to transcription change incomplete\", \"Contribution of HMGN2 redundancy not fully separated\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Established HMGN1 as a dosage-sensitive oncogenic driver in Down syndrome-associated leukemia via PRC2 antagonism.\",\n      \"evidence\": \"Mouse trisomy and HMGN1-overexpression models, ChIP-seq for H3K27me3, bone-marrow transplant leukemia models, with human B-ALL validation\",\n      \"pmids\": [\"24747640\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct mechanism of H3K27me3 suppression by HMGN1 not biochemically defined here\", \"Whether effect is restricted to B-cell context unclear\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Resolved the long-standing question of how HMGN1 antagonizes H1 — by co-occupancy and altered condensation rather than displacement.\",\n      \"evidence\": \"Salt-induced compaction/self-association assays, H1 displacement assays, hydroxyl radical footprinting, and analytical ultracentrifugation\",\n      \"pmids\": [\"28973435\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo relevance of co-occupancy not directly tested\", \"How altered tail positions translate to enzyme accessibility unresolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Showed HMGN1 overexpression globally amplifies transcription and raises H3K27 acetylation, and is necessary for Down syndrome B-cell phenotypes.\",\n      \"evidence\": \"Absolute spike-in normalized ChIP-Rx (H3K27ac) and RNA-seq across DS trisomy and HMGN1-overexpression/KO models\",\n      \"pmids\": [\"30428356\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism linking HMGN1 dosage to global H3K27ac increase not defined\", \"Causal direction between acetylation and transcription amplification unresolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Refuted the requirement for HMGN1 in human transcription-coupled DNA repair, qualifying the earlier mouse NER role.\",\n      \"evidence\": \"HMGN1/2 KO and knockdown human cells, UV and Illudin S sensitivity, transcription restart, GFP-HMGN1 damage recruitment imaging, and TCR-complex Co-IP\",\n      \"pmids\": [\"32152397\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Species/context differences from earlier mouse NER findings not reconciled\", \"Does not exclude repair roles outside the TCR pathway\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Characterized how phosphorylation reshapes the disordered binding domain, showing local and long-range conformational effects with only minor in vitro binding changes.\",\n      \"evidence\": \"NMR, CD, protein semi-synthesis with site-specific PTMs, segmental isotope labeling, and nucleosome binding assays\",\n      \"pmids\": [\"34458797\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional readout of conformational changes beyond binding unknown\", \"In-cell consequence of long-range perturbation untested\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Extended HMGN1's open-chromatin function to viral episomes, showing it maintains HBV cccDNA accessibility by limiting H3 phosphorylation.\",\n      \"evidence\": \"ChIP, FISH, HMGN1 domain-mutant analysis, CLK2/H3 phosphorylation measurement, and in vivo mouse HBV model\",\n      \"pmids\": [\"38181856\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single-system viral finding\", \"Direct vs indirect effect on CLK2 not resolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Provided structural-level mechanism for phospho-regulation, showing binding-domain phosphorylation disrupts the HMGN1-acidic patch interface.\",\n      \"evidence\": \"NMR, CD with site-specific phospho-peptides, and AlphaFold3 complex modeling\",\n      \"pmids\": [\"39186607\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No in-cell validation of acidic-patch disruption\", \"Quantitative affinity change not measured\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined the modification preference and PRC2-antagonizing biochemistry of HMGN1, and established its dosage role in cardiac development.\",\n      \"evidence\": \"Isogenic Hmgn1/Hmgn2 KO mESCs with modified-nucleosome binding and p300 assays, epiproteomic MS and RNA-seq; iPSC cardiac differentiation, CROP-seq screen, and Hmgn1 allele deletion in trisomy 21 mice rescuing valvuloseptal defects\",\n      \"pmids\": [\"41325801\", \"41125893\", \"30428356\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How preferential binding to acetylated/H2A.Z nucleosomes is achieved structurally not fully defined\", \"Mechanism connecting reduced p300 acetylation to increased H3K27 methylation unresolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how HMGN1 selects shared versus unique genomic targets relative to HMGN2 and how its dosage is quantitatively translated into global transcriptional amplification and tissue-specific developmental outcomes.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Target-selection determinants between HMGN1 and HMGN2 undefined\", \"Quantitative dose-response relationship linking HMGN1 levels to global transcription and PRC2 antagonism not established\", \"Structural basis for preferential binding to specific modified nucleosomes incomplete\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [3, 9]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 7, 29]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [5, 38]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [15, 16, 25, 37]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [21, 26]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [10, 12]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [0, 23, 27]},\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [23, 27]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [16, 29, 37]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [5, 27, 38]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [10, 12, 18]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [28, 36]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"HMGN2\", \"PARP1\", \"PCNA\", \"EP300\", \"ESR1\", \"SRF\", \"MSK1\", \"PCAF\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":8,"faith_total":8,"faith_pct":100.0}}