Affinage

HMGN1

Non-histone chromosomal protein HMG-14 · UniProt P05114

Length
100 aa
Mass
10.7 kDa
Annotated
2026-06-10
94 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1980 High

    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

    PMID:6449690

    Open questions at the time
    • Did not resolve which histones or DNA regions are contacted
    • Did not establish a functional consequence of binding
  2. 1994 High

    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

    PMID:7971283 PMID:8047885 PMID:8107104

    Open questions at the time
    • Did not identify which enzymes the open chromatin affects in vivo
    • Domain-specific histone contacts not yet resolved
  3. 1997 High

    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)

    PMID:9315642

    Open questions at the time
    • Whether H1 is displaced or co-bound was not resolved until later
    • In vivo relevance of minichromosome findings untested
  4. 1998 High

    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

    PMID:9576905 PMID:9852141

    Open questions at the time
    • Trigger controlling mitotic chromatin release not yet identified
    • Functional purpose of cell-cycle exclusion unclear
  5. 2002 High

    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

    PMID:12215538

    Open questions at the time
    • Kinase responsible for mitotic phosphorylation not identified here
    • Functional 14-3-3 isoform specificity in vivo unresolved
  6. 2003 High

    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

    PMID:12660172 PMID:12773393

    Open questions at the time
    • NER role later contradicted in human cells
    • How accessibility increase recruits NER factors mechanistically not detailed
  7. 2000 High

    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

    PMID:10753971

    Open questions at the time
    • In vivo stoichiometry and dynamics of HMGN1 acetylation unknown
    • Crosstalk with phosphorylation not addressed
  8. 2004 High

    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

    PMID:15327773 PMID:16096646 PMID:17154547

    Open questions at the time
    • Whether modulation is steric or via altered tail positioning not resolved here
    • Net transcriptional outcome of opposing PTM effects unclear
  9. 2005 High

    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

    PMID:16061652 PMID:16279949

    Open questions at the time
    • Direct chromatin targets driving phenotypes incompletely defined
    • N-cadherin regulation evidence Medium-confidence
  10. 2006 High

    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

    PMID:16382150

    Open questions at the time
    • Mechanism of HMGN1-vs-HMGN2 target selection unknown
    • Direct vs indirect Sox9 regulation not fully separated
  11. 2007 High

    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

    PMID:17938209

    Open questions at the time
    • Generality of TF-mediated recruitment across the genome not established
    • Direct vs nucleosome-mediated TF contact unresolved
  12. 2008 Medium

    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

    PMID:18218636

    Open questions at the time
    • Single-promoter focus
    • Whether HMGN1 recruits or merely enables the HAT not distinguished
  13. 2012 High

    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

    PMID:22393258 PMID:22736760

    Open questions at the time
    • Whether these interactions are direct on chromatin in vivo not fully resolved
    • Functional consequence for repair outcome in human cells later questioned
  14. 2010 High

    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

    PMID:21173166

    Open questions at the time
    • Did not establish whether HMGN1 creates or reads accessibility
    • Sequence determinants of binding not defined
  15. 2013 High

    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

    PMID:23775126

    Open questions at the time
    • Causal chain from nucleosome destabilization to transcription change incomplete
    • Contribution of HMGN2 redundancy not fully separated
  16. 2014 High

    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

    PMID:24747640

    Open questions at the time
    • Direct mechanism of H3K27me3 suppression by HMGN1 not biochemically defined here
    • Whether effect is restricted to B-cell context unclear
  17. 2017 High

    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

    PMID:28973435

    Open questions at the time
    • In vivo relevance of co-occupancy not directly tested
    • How altered tail positions translate to enzyme accessibility unresolved
  18. 2018 High

    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

    PMID:30428356

    Open questions at the time
    • Mechanism linking HMGN1 dosage to global H3K27ac increase not defined
    • Causal direction between acetylation and transcription amplification unresolved
  19. 2020 High

    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

    PMID:32152397

    Open questions at the time
    • Species/context differences from earlier mouse NER findings not reconciled
    • Does not exclude repair roles outside the TCR pathway
  20. 2021 High

    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

    PMID:34458797

    Open questions at the time
    • Functional readout of conformational changes beyond binding unknown
    • In-cell consequence of long-range perturbation untested
  21. 2023 Medium

    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

    PMID:38181856

    Open questions at the time
    • Single-system viral finding
    • Direct vs indirect effect on CLK2 not resolved
  22. 2024 Medium

    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

    PMID:39186607

    Open questions at the time
    • No in-cell validation of acidic-patch disruption
    • Quantitative affinity change not measured
  23. 2025 High

    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

    PMID:30428356 PMID:41125893 PMID:41325801

    Open questions at the time
    • How preferential binding to acetylated/H2A.Z nucleosomes is achieved structurally not fully defined
    • Mechanism connecting reduced p300 acetylation to increased H3K27 methylation unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • 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.
  • 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

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0003677 DNA binding 2 GO:0042393 histone binding 2 GO:0060090 molecular adaptor activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 2 GO:0005654 nucleoplasm 2
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1643685 Disease 2
Partners
EP300ESR1HMGN2MSK1PARP1PCAFPCNASRF

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1980 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. Thermal denaturation, nuclease digestion, nucleosome binding assays with chicken erythrocyte chromatin Nucleic acids research High 6449690
1980 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). 270-MHz NMR, circular dichroism European journal of biochemistry Medium 6257511
1981 HMGN1 (HMG-14) preferentially binds single-stranded DNA over double-stranded DNA, as demonstrated by sequential affinity chromatography. Sequential affinity chromatography on immobilized ss- and ds-DNA columns with purified protein Nucleic acids research Medium 7279673
1985 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. Reconstitution and chemical crosslinking with photoactivable reagents in chromatin Biochemical and biophysical research communications Medium 4074344
1994 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. Hydroxyl radical footprinting of HMG-14/-17 on nucleosome cores and chromatosomes Journal of molecular biology High 8107104
1994 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. In vitro transcription assays on in vivo-assembled chromatin templates vs. DNA templates Science (New York, N.Y.) High 8047885
1994 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. In vivo phosphorylation mapping, micrococcal nuclease fractionation, in vitro kinase assay on isolated mononucleosomes The EMBO journal High 7925294
1994 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. Site-directed mutagenesis + nucleosome core binding assays Nucleic acids research High 7971283
1997 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. SV40 minichromosome transcription assays, chromatin compaction assays, domain-swap experiments Molecular and cellular biology High 9315642
1998 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. Protein photocrosslinking in nucleosome cores Proceedings of the National Academy of Sciences of the United States of America High 9576905
1998 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. Immunofluorescence cell cycle analysis, reconstituted nuclei nuclear import assays, permeabilized cell import assays The Journal of cell biology High 9852141
2000 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. In vitro acetyltransferase assays with purified p300, mass spectrometry of acetylation sites, nucleosome binding assays with acetylated protein, in vivo acetylation analysis The Journal of biological chemistry High 10753971
2002 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. Immunofluorescence, in vitro nuclear import assays with microinjected WT and mutant proteins, affinity chromatography with recombinant proteins and mitotic cell extracts Molecular and cellular biology High 12215538
2003 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. Genetic knockout (MSK1-/-, MSK2-/-, double KO mice), phosphorylation assays in Coffin-Lowry cells and mouse fibroblasts The EMBO journal High 12773393
2003 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. Hmgn1-/- MEFs UV sensitivity assay, photoproduct removal kinetics, host cell reactivation, NER pathway analysis, mutant HMGN1 rescue transfections, nuclease accessibility assays The EMBO journal High 12660172
2004 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. In vitro kinase assays on nucleosomal vs. free H3, Hmgn1-/- cell western analysis, in vivo phosphorylation kinetics Molecular cell High 15327773
2005 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. In vitro PCAF acetyltransferase assays on nucleosomes vs. free H3, Hmgn1-/- cell rescue with WT vs. mutant HMGN1, western analysis of H3K14ac The EMBO journal High 16096646
2005 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. Hmgn1-/- MEFs, DNA microarray, RT-PCR, western blot, mutant rescue, cell adhesion/motility assays The FEBS journal Medium 16279949
2005 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. Hmgn1-/- mouse model, ionizing radiation survival, tumor incidence, cell cycle checkpoint analysis, mutant rescue transfections Cancer research High 16061652
2006 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. In vitro kinase assays with Rsk2 and Msk1 on nucleosomal vs. free H2A, Hmgn1-/- cell western analysis, chromatin-binding mutant controls Biochemistry High 17154547
2006 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. Hmgn1-/- limb bud micromass cultures, ChIP assay, mutant rescue, gene expression analysis Molecular and cellular biology High 16382150
2007 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. Co-immunoprecipitation, in vitro binding assay, ChIP, knockdown and overexpression, histone modification analysis Molecular and cellular biology High 17938209
2008 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. Hmgn1-/- vs. +/+ MEFs, RT-PCR, ChIP for H3K14ac at Hsp70, HDAC inhibitor treatment The Journal of biological chemistry Medium 18218636
2010 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. ChIP-seq, DNase I hypersensitivity mapping, comparison to regulatory chromatin marks Molecular and cellular biology High 21173166
2011 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). Hmgn1 overexpressing and KO mouse brain tissue and cell lines, qPCR, western blot, ChIP, behavioral tests The Journal of biological chemistry Medium 22009741
2012 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. 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 The Journal of biological chemistry High 22736760
2012 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. Co-IP/pulldown, deletion mutagenesis, chromatin binding assays, live-cell imaging (PCNA recruitment to laser damage sites) in Hmgn1-/- vs. +/+ cells Molecular and cellular biology High 22393258
2013 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. MNase-seq, DNase-seq, RNA-seq in Hmgn1-/- vs. +/+ ESCs and neural progenitors, neurosphere assays Molecular and cellular biology High 23775126
2014 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. Mouse trisomy models, HMGN1 overexpression constructs, ChIP-seq for H3K27me3, bone marrow transplantation/leukemia in vivo models Nature genetics High 24747640
2017 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. Salt-induced compaction and self-association assays, H1 displacement assays, hydroxyl radical footprinting, analytical ultracentrifugation Nucleic acids research High 28973435
2018 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). Absolute exogenous spike-in normalized ChIP-Rx (H3K27ac) and RNA-seq in DS trisomy and HMGN1-overexpression models Cell reports High 30428356
2018 Extracellular HMGN1 acts as a TLR4 agonist and promotes dendritic cell recruitment through a Gαi protein-coupled receptor; it preferentially drives Th1-type immunity. TLR4 binding/signaling assays, DC recruitment assays, DC maturation assays Seminars in immunology Medium 29503123
2020 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. 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 Scientific reports High 32152397
2021 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. NMR spectroscopy, circular dichroism, protein semi-synthesis for site-specific PTMs, segmental isotope labeling, nucleosome binding assays RSC chemical biology High 34458797
2023 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. ChIP, FISH, functional HMGN1 mutant analysis, CLK2/H3 phosphorylation measurement, in vivo mouse HBV model Antiviral research Medium 38181856
2024 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. NMR spectroscopy, circular dichroism, AlphaFold3 complex modeling Chembiochem Medium 39186607
2025 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. Human iPSC cardiac differentiation, CRISPR-activation CROP-seq screen of chr21 genes, single-cell RNA-seq, Hmgn1 allele deletion in trisomy 21 mouse Nature High 41125893
2025 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. Engineered Hmgn1-/-, Hmgn2-/-, and Hmgn1-/-Hmgn2-/- mESCs, nucleosome binding assays (modified nucleosomes), in vitro acetylation assays with p300, epiproteomic MS, RNA-seq The Journal of biological chemistry High 41325801
2025 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. HMGN null human cell line generation, isogenic HMGN1/HMGN2 rescue lines, genome-wide transcriptomic analysis, promoter/enhancer mapping bioRxivpreprint Medium bio_10.1101_2025.11.27.690916

Source papers

Stage 0 corpus · 94 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14. The EMBO journal 411 12773393
1980 The interaction of high mobility proteins HMG14 and 17 with nucleosomes. Nucleic acids research 226 6449690
2003 Chromosomal protein HMGN1 enhances the rate of DNA repair in chromatin. The EMBO journal 125 12660172
2004 Chromosomal protein HMGN1 modulates histone H3 phosphorylation. Molecular cell 107 15327773
2014 Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation. Nature genetics 100 24747640
1980 Structural studies on two high-mobility-group proteins from calf thymus, HMG-14 and HMG-20 (ubiquitin), and their interaction with DNA. European journal of biochemistry 89 6257511
2005 Chromosomal protein HMGN1 enhances the acetylation of lysine 14 in histone H3. The EMBO journal 81 16096646
1997 Alleviation of histone H1-mediated transcriptional repression and chromatin compaction by the acidic activation region in chromosomal protein HMG-14. Molecular and cellular biology 81 9315642
1994 Stimulation of RNA polymerase II elongation by chromosomal protein HMG-14. Science (New York, N.Y.) 77 8047885
2005 Increased tumorigenicity and sensitivity to ionizing radiation upon loss of chromosomal protein HMGN1. Cancer research 66 16061652
2006 Down-regulation of nucleosomal binding protein HMGN1 expression during embryogenesis modulates Sox9 expression in chondrocytes. Molecular and cellular biology 60 16382150
1994 The footprint of chromosomal proteins HMG-14 and HMG-17 on chromatin subunits. Journal of molecular biology 60 8107104
1990 Linkage analysis of the human HMG14 gene on chromosome 21 using a GT dinucleotide repeat as polymorphic marker. Genomics 60 1970797
2000 Acetylation of novel sites in the nucleosomal binding domain of chromosomal protein HMG-14 by p300 alters its interaction with nucleosomes. The Journal of biological chemistry 57 10753971
1998 The chromatin unfolding domain of chromosomal protein HMG-14 targets the N-terminal tail of histone H3 in nucleosomes. Proceedings of the National Academy of Sciences of the United States of America 56 9576905
2014 The Alarmin HMGN1 contributes to antitumor immunity and is a potent immunoadjuvant. Cancer research 54 25205103
1998 Chromosomal proteins HMG-14 and HMG-17 are released from mitotic chromosomes and imported into the nucleus by active transport. The Journal of cell biology 52 9852141
2018 Trisomy of a Down Syndrome Critical Region Globally Amplifies Transcription via HMGN1 Overexpression. Cell reports 47 30428356
2017 HMGN1 and 2 remodel core and linker histone tail domains within chromatin. Nucleic acids research 46 28973435
1994 A mitogen- and anisomycin-stimulated kinase phosphorylates HMG-14 in its basic amino-terminal domain in vivo and on isolated mononucleosomes. The EMBO journal 46 7925294
2011 The chromatin-binding protein HMGN1 regulates the expression of methyl CpG-binding protein 2 (MECP2) and affects the behavior of mice. The Journal of biological chemistry 43 22009741
2010 Genomic profiling of HMGN1 reveals an association with chromatin at regulatory regions. Molecular and cellular biology 43 21173166
2019 Combining Rapid Data Independent Acquisition and CRISPR Gene Deletion for Studying Potential Protein Functions: A Case of HMGN1. Proteomics 39 30901150
1986 Chromosomal protein HMG-14. Complete human cDNA sequence and evidence for a multigene family. The Journal of biological chemistry 39 3782107
1979 The complete amino-acid sequence of a trout-testis non-histone protein, H6, localized in a subset of nucleosomes and its similarity to calf-thymus non-histone proteins HMG-14 and HMG-17. European journal of biochemistry 39 456349
2018 HMGN1 and R848 Synergistically Activate Dendritic Cells Using Multiple Signaling Pathways. Frontiers in immunology 36 30619338
2012 HMGN1 protein regulates poly(ADP-ribose) polymerase-1 (PARP-1) self-PARylation in mouse fibroblasts. The Journal of biological chemistry 36 22736760
1989 Chromosomal protein HMG-14. Identification, characterization, and chromosome localization of a functional gene from the large human multigene family. The Journal of biological chemistry 36 2563381
1990 Chromosomal protein HMG-14 gene maps to the Down syndrome region of human chromosome 21 and is overexpressed in mouse trisomy 16. Proceedings of the National Academy of Sciences of the United States of America 35 2140193
2013 HMGN1 modulates nucleosome occupancy and DNase I hypersensitivity at the CpG island promoters of embryonic stem cells. Molecular and cellular biology 34 23775126
2002 Mitotic phosphorylation of chromosomal protein HMGN1 inhibits nuclear import and promotes interaction with 14.3.3 proteins. Molecular and cellular biology 34 12215538
2010 Retinoic acid controls expression of tissue remodeling genes Hmgn1 and Fgf18 at the digit-interdigit junction. Developmental dynamics : an official publication of the American Association of Anatomists 32 20034106
1991 Recombinant human chromosomal proteins HMG-14 and HMG-17. Nucleic acids research 31 2057367
2021 Combining an Alarmin HMGN1 Peptide with PD-L1 Blockade Results in Robust Antitumor Effects with a Concomitant Increase of Stem-Like/Progenitor Exhausted CD8+ T Cells. Cancer immunology research 29 34344641
1992 Genetic mapping of the murine gene and 14 related sequences encoding chromosomal protein HMG-14. Mammalian genome : official journal of the International Mammalian Genome Society 29 1360278
1981 Nonhistone chromatin proteins HMG-14 and HMG-17 bind preferentially to single-stranded DNA. Nucleic acids research 29 7279673
2021 A TNFR2 antibody by countering immunosuppression cooperates with HMGN1 and R848 immune stimulants to inhibit murine colon cancer. International immunopharmacology 28 34794079
2018 High-mobility group nucleosome binding domain 1 (HMGN1) functions as a Th1-polarizing alarmin. Seminars in immunology 28 29503123
1980 The isolation, characterization and partial sequences of the chicken erythrocyte non-histone chromosomal proteins HMG14 and HMG17. Comparison with the homologous calf thymus proteins. The Biochemical journal 28 7396821
2015 High mobility group B1 and N1 (HMGB1 and HMGN1) are associated with tumor-infiltrating lymphocytes in HER2-positive breast cancers. Virchows Archiv : an international journal of pathology 27 26445971
2008 Chromosomal protein HMGN1 enhances the heat shock-induced remodeling of Hsp70 chromatin. The Journal of biological chemistry 26 18218636
2006 A role for chromosomal protein HMGN1 in corneal maturation. Differentiation; research in biological diversity 26 16466397
2023 Acteoside alleviates UUO-induced inflammation and fibrosis by regulating the HMGN1/TLR4/TREM1 signaling pathway. PeerJ 25 36691481
1986 Chromosomal proteins HMG-14 and HMG-17. Distinct multigene families coding for similar types of transcripts. The Journal of biological chemistry 25 3782108
2007 HMGN1 modulates estrogen-mediated transcriptional activation through interactions with specific DNA-binding transcription factors. Molecular and cellular biology 24 17938209
2005 Chromosomal protein HMGN1 modulates the expression of N-cadherin. The FEBS journal 23 16279949
1994 The cooperative binding of chromosomal protein HMG-14 to nucleosome cores is reduced by single point mutations in the nucleosomal binding domain. Nucleic acids research 23 7971283
2006 Chromosomal protein HMGN1 modulates the phosphorylation of serine 1 in histone H2A. Biochemistry 22 17154547
1981 The characterisation of 1SF monomer nucleosomes from hen oviduct and the partial characterisation of a third HMG14/17-like in such nucleosomes. Nucleic acids research 21 6456450
2021 HMGN1 plays a significant role in CRLF2 driven Down Syndrome leukemia and provides a potential therapeutic target in this high-risk cohort. Oncogene 20 34857887
1988 Cloning of the chicken chromosomal protein HMG-14 cDNA reveals a unique protein with a conserved DNA binding domain. The Journal of biological chemistry 20 3417670
2023 HMGN1 enhances CRISPR-directed dual-function A-to-G and C-to-G base editing. Nature communications 19 37105976
1990 Interaction of HMG14 with chromatin. Journal of molecular biology 17 2388273
2012 The nucleosome binding protein HMGN1 interacts with PCNA and facilitates its binding to chromatin. Molecular and cellular biology 16 22393258
1995 Characterization of transgenic mice with an increased content of chromosomal protein HMG-14 in their chromatin. DNA and cell biology 16 8534374
1993 Reconstitution of short-spaced chromatin from the histone octamer and either HMG-14,17 or histone H1. Journal of molecular biology 16 8478937
2019 Combined treatment with HMGN1 and anti-CD4 depleting antibody reverses T cell exhaustion and exerts robust anti-tumor effects in mice. Journal for immunotherapy of cancer 15 30696484
2015 Hmgn1 acts downstream of C/EBPβ to regulate the decidualization of uterine stromal cells in mice. Cell cycle (Georgetown, Tex.) 15 26566865
1988 Chicken chromosomal protein HMG-14 and HMG-17 cDNA clones: isolation, characterization and sequence comparison. Gene 15 3384337
2005 Effects of HMGN1 on chromatin structure and SWI/SNF-mediated chromatin remodeling. The Journal of biological chemistry 14 16253989
2024 HMGN1 down-regulation in the diabetic kidney attenuates tubular cells injury and protects against renal inflammation via suppressing MCP-1 and KIM-1 expression through TLR4. Journal of endocrinological investigation 13 38409569
2018 IGF-1R Inhibitor Ameliorates Diabetic Nephropathy with Suppressed HMGN1/TLR4 Pathway. Endocrine, metabolic & immune disorders drug targets 13 29384065
2021 Site-specific modification and segmental isotope labelling of HMGN1 reveals long-range conformational perturbations caused by posttranslational modifications. RSC chemical biology 12 34458797
2013 Loss of the nucleosome-binding protein HMGN1 affects the rate of N-nitrosodiethylamine-induced hepatocarcinogenesis in mice. Molecular cancer research : MCR 12 24296759
1991 Chromosomal protein HMG-14 is overexpressed in Down syndrome. Experimental cell research 12 1825298
1985 Binding of HMG14 non-histone protein to histones H2A, H2B, H1 and DNA in reconstituted chromatin. Biochemical and biophysical research communications 12 4074344
2009 Expression of nucleosomal protein HMGN1 in the cycling mouse hair follicle. Gene expression patterns : GEP 11 19303948
2013 Nucleosome structural changes induced by binding of non-histone chromosomal proteins HMGN1 and HMGN2. FEBS open bio 10 23772392
2003 Status of the "protein kinase CK2-HMG14" system in age-related amnesia in rats. Neuroscience and behavioral physiology 10 14635996
2023 Anti-TNFR2 enhanced the antitumor activity of a new HMGN1/3M-052 stimulated dendritic cell vaccine in a mouse model of colon cancer. Biochemical and biophysical research communications 9 36868074
2023 Gain of chromosome 21 increases the propensity for P2RY8::CRLF2 acute lymphoblastic leukemia via increased HMGN1 expression. Frontiers in oncology 9 37483494
2022 Shaking up the silence: consequences of HMGN1 antagonizing PRC2 in the Down syndrome brain. Epigenetics & chromatin 9 36463299
1990 Expression of chromosomal proteins HMG-14 and HMG-17 in transformed human cells. Cancer research 8 2317791
2020 Human HMGN1 and HMGN2 are not required for transcription-coupled DNA repair. Scientific reports 7 32152397
2024 Chromatin binding protein HMGN1 promotes HBV cccDNA transcription and replication by regulating the phosphorylation of histone 3. Antiviral research 6 38181856
2024 KAT7/HMGN1 signaling epigenetically induces tyrosine phosphorylation-regulated kinase 1A expression to ameliorate insulin resistance in Alzheimer's disease. World journal of psychiatry 5 38617985
2006 HMGN1 is dispensable for myogenesis and adipogenesis. Gene 5 16451822
2025 Myocardial reprogramming by HMGN1 underlies heart defects in trisomy 21. Nature 4 41125893
2003 The in vitro reconstitution of nucleosome and its binding patterns with HMG1/2 and HMG14/17 proteins. Cell research 4 14672558
2024 HMGN1 loss sensitizes lung cancer cells to chemotherapy. Scientific reports 3 38710740
2025 Anti-TNFR2 antibody and HMGN1 combined with TIL cell therapy inhibits colorectal cancer progression by enhancing immune response. Biochemical and biophysical research communications 2 40483876
2023 The growth hormone receptor interacts with transcriptional regulator HMGN1 upon GH-induced nuclear translocation. Journal of cell communication and signaling 2 37043098
2021 Function of chromatin modifier Hmgn1 during neural crest and craniofacial development. Genesis (New York, N.Y. : 2000) 2 34478234
2021 Camostat mesilate inhibits pro-inflammatory cytokine secretion and improves cell viability by regulating MFGE8 and HMGN1 in lipopolysaccharide-stimulated DF-1 chicken embryo fibroblasts. PeerJ 2 34527443
1993 Evolutionarily conserved motifs and protein binding elements in the 5' region of the chromosomal protein HMG-14 gene. DNA and cell biology 2 8397832
2025 HMGN1 and HMGN2 are recruited to acetylated and histone variant H2A.Z-containing nucleosomes to regulate chromatin state and transcription. The Journal of biological chemistry 1 41325801
2024 Phosphorylation of the HMGN1 Nucleosome Binding Domain Decreases Helicity and Interactions with the Acidic Patch. Chembiochem : a European journal of chemical biology 1 39186607
1996 Chromosomal proteins HMG-14 and HMG-17 are synthesized throughout the S-phase in Burkitt's lymphoma. Biochemical and biophysical research communications 1 8670211
1990 Expression of human chromosomal proteins HMG-14 and HMG-17 in Saccharomyces cerevisiae. Experimental cell research 1 2226652
2026 Chromatin-binding protein HMGN1 promotes HCC tumorigenesis via histone methylation-induced RALB transcriptional suppression. Journal of genetics and genomics = Yi chuan xue bao 0 41833635
2026 Combination of APS, HMGN1, and anti-TNFR2 antibody remodels the tumor immune microenvironment to enhance antitumor immunity in colorectal cancer. Translational oncology 0 42150331
2025 Identification of a Novel RUNX1::HMGN1 Fusion in Therapy Acute Myeloid Leukemia. Molecular carcinogenesis 0 41252680
2024 [High mobility group nucleosome binding protein 1 (HMGN1) induces activation of mouse BV2 microglia and upregulates their pro-inflammatory mediator expression by activating TLR4/MyD88/NF-κB p65/IKK-β signal pathway]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 38284254
2002 [State of the "protein kinase CK2-HMG14" system in age-dependent amnesia in rats]. Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova 0 12136729

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