Affinage

HMGN1

Non-histone chromosomal protein HMG-14 · UniProt P05114

Length
100 aa
Mass
10.7 kDa
Annotated
2026-04-28
93 papers in source corpus 35 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HMGN1 is a nucleosome-binding architectural protein that modulates chromatin accessibility, histone modification landscapes, and transcriptional output across diverse cellular contexts including DNA repair, cell-cycle progression, and differentiation. It binds specifically to nucleosome core particles (two molecules per core) via its nucleosomal binding domain (NBD), which contacts the nucleosome acidic patch and histone H2B, while its acidic C-terminal domain contacts the histone H3 N-terminal tail to counteract linker histone H1-mediated chromatin compaction without displacing H1 (PMID:6449690, PMID:9576905, PMID:28973435). HMGN1 shapes the histone modification landscape by hindering kinase access to nucleosomal H3-S10 and H2A-S1 (reducing their phosphorylation), enhancing HAT-mediated acetylation of H3K14, stimulating global H3K27 acetylation, and antagonizing PRC2-dependent H3K27 trimethylation—activities that preferentially target active promoters, CpG island-containing promoters, enhancers, and DNase I hypersensitive sites (PMID:15327773, PMID:16096646, PMID:24747640, PMID:30428356, PMID:21173166). Its chromatin association is dynamically regulated: mitotic phosphorylation of the NBD by MSK1/MSK2 reduces helical propensity, disrupts the acidic-patch interface, promotes 14-3-3 binding to block nuclear re-import, and p300-mediated acetylation of the NBD independently weakens nucleosome affinity; overexpression of HMGN1 from chromosome 21 trisomy drives B-cell acute lymphoblastic leukemia in mouse models and causes valvuloseptal heart defects in Down syndrome by shifting cardiomyocyte transcriptional identity (PMID:12215538, PMID:34458797, PMID:24747640, PMID:41125893).

Mechanistic history

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

    Establishing that HMGN1 is a specific nucleosome-binding protein—rather than a general DNA-binding factor—answered whether its chromatin association is structural and selective, showing two molecules bind cooperatively per core particle with preference for transcriptionally active sequences.

    Evidence Thermal denaturation, nuclease digestion, and nucleosome reconstitution with gene-sequence enrichment; NMR/CD showing intrinsic disorder and N-terminal DNA contact

    PMID:6257511 PMID:6449690

    Open questions at the time
    • Precise residues mediating nucleosome specificity not yet mapped
    • In vivo stoichiometry not confirmed
    • Mechanism of preference for active chromatin unknown
  2. 1994 High

    Mapping HMGN1 footprints on nucleosomes and demonstrating that it enhances RNA Pol II elongation on chromatin templates (not naked DNA) established the structural basis and functional consequence of nucleosome binding, while mutagenesis of the NBD proved this domain is essential for cooperative binding.

    Evidence Hydroxyl radical footprinting on cores/chromatosomes; in vitro transcription on chromatin vs DNA templates; site-directed mutagenesis with mobility-shift assays

    PMID:7971283 PMID:8047885 PMID:8107104

    Open questions at the time
    • How NBD conformation enables cooperative binding at atomic level not resolved
    • Whether elongation enhancement operates in vivo unclear
  3. 1994 High

    Discovery that mitogen-stimulated serine phosphorylation of HMGN1 occurs in its N-terminal region, catalyzed by a nucleosome-associated kinase, revealed that post-translational modification regulates HMGN1–chromatin dynamics.

    Evidence In vivo metabolic labeling with mononucleosome fractionation and in vitro kinase assay

    PMID:7925294

    Open questions at the time
    • Identity of the kinase not yet determined
    • Functional consequence of phosphorylation for chromatin structure unknown
  4. 1997 High

    Showing that the acidic C-terminal domain alleviates H1-mediated transcriptional repression and disrupts chromatin compaction—with function maintained when replaced by heterologous acidic domains—established a modular architecture: NBD for nucleosome targeting, C-terminal domain for chromatin unfolding.

    Evidence In vitro transcription on SV40 minichromosomes, chromatin compaction assay, domain-swap mutagenesis

    PMID:9315642

    Open questions at the time
    • Direct histone contacts of C-terminal domain not mapped
    • Whether H1 is displaced or merely antagonized in cis unknown
  5. 1998 High

    Photocrosslinking identified specific histone contacts—N-terminal domain to H2B and C-terminal chromatin-unfolding domain to the H3 N-terminal tail—providing the first molecular map of how HMGN1 domains interact with distinct histone surfaces.

    Evidence Protein photocrosslinking in reconstituted nucleosome cores

    PMID:9576905

    Open questions at the time
    • Atomic-resolution structure of full complex not available
    • Whether contacts differ in dinucleosome/chromatin fiber context unknown
  6. 1998 High

    Demonstrating that HMGN1 dissociates from chromosomes during mitosis and re-enters nuclei via an importin-α-dependent NLS pathway established that chromatin binding is cell-cycle regulated.

    Evidence Immunofluorescence cell-cycle staging, reconstituted nuclei import assay with energy/importin depletion

    PMID:9852141

    Open questions at the time
    • What triggers mitotic release not identified
    • Whether re-association is random or targeted to specific loci unknown
  7. 2000 High

    Identification of p300-mediated acetylation of HMGN1 at seven sites including three in the NBD, with acetylation weakening nucleosome binding, revealed a second PTM axis (alongside phosphorylation) that tunes HMGN1–chromatin affinity.

    Evidence In vitro p300 acetylation, site identification, nucleosome binding assay comparing acetylated and unacetylated protein

    PMID:10753971

    Open questions at the time
    • In vivo acetylation dynamics not characterized
    • Whether acetylation and phosphorylation act combinatorially unknown
  8. 2002 High

    Showing that mitotic NBD phosphorylation prevents nuclear re-entry via phosphorylation-dependent 14-3-3 binding (not charge effects) explained how HMGN1 is excluded from reforming nuclei until dephosphorylation occurs.

    Evidence In vitro nuclear import with phosphomimetic mutants, affinity chromatography with mitotic vs logarithmic extracts

    PMID:12215538

    Open questions at the time
    • Identity of the phosphatase that restores import competence unknown
    • Which 14-3-3 isotype is physiologically relevant in vivo not resolved
  9. 2003 High

    MSK1 and MSK2 were identified as the major kinases for HMGN1 phosphorylation upon mitogenic and stress stimulation, resolving the kinase identity question; separately, HMGN1 was shown to enhance nucleotide excision repair by reducing chromatin compaction, with Hmgn1-/- cells UV-hypersensitive.

    Evidence MSK1/MSK2 double-KO mouse fibroblasts with in vivo phosphorylation assay; Hmgn1-/- MEFs with UV survival and photoproduct removal assays, rescue with WT vs NBD-mutant

    PMID:12660172 PMID:12773393

    Open questions at the time
    • Whether MSK1/2 phosphorylation of HMGN1 directly enables NER factor access not tested
    • Species specificity of NER role not yet apparent
  10. 2004 High

    Demonstrating that HMGN1 reduces H3-S10 phosphorylation by sterically impeding kinase access to nucleosomal (but not free) H3, and that stress-induced HMGN1 phosphorylation transiently relieves this block, established a dynamic gating mechanism for histone modification.

    Evidence Hmgn1-/- MEFs, in vitro kinase assay on nucleosomal vs free H3, anisomycin kinetics, chromatin fractionation

    PMID:15327773

    Open questions at the time
    • Whether this gating applies genome-wide or at specific loci unknown
    • Which kinases are gated in vivo not fully defined
  11. 2005 High

    HMGN1 was shown to enhance PCAF-mediated H3K14 acetylation on nucleosomes (not free H3), increase ionizing radiation sensitivity with impaired G2/M checkpoint activation, and negatively regulate N-cadherin expression—broadening its functional scope to HAT facilitation, DNA damage checkpoints, and cell adhesion.

    Evidence Hmgn1-/- MEFs with in vitro PCAF acetylation on nucleosomes, IR survival and checkpoint assay, microarray and RT-PCR for N-cadherin, rescue with WT vs mutant HMGN1

    PMID:16061652 PMID:16096646 PMID:16279949

    Open questions at the time
    • Whether HAT facilitation and kinase gating are mechanistically linked not tested
    • Checkpoint phenotype not connected to specific histone modifications
  12. 2006 High

    Extension of the kinase-gating model to H2A-S1 phosphorylation (elevated in Hmgn1-/- cells) and the discovery that HMGN1 occupies Sox9 chromatin during embryogenesis to restrain chondrogenic differentiation established HMGN1 as a lineage-specific chromatin modulator.

    Evidence In vitro Rsk2/Msk1 kinase assay on nucleosomal vs free H2A; Hmgn1-/- limb bud micromass cultures with ChIP at Sox9 locus, rescue with WT vs mutant

    PMID:16382150 PMID:17154547

    Open questions at the time
    • Whether HMGN1 directly competes with HMGN2 at Sox9 in a zero-sum manner not resolved
    • How HMGN1 is targeted to Sox9 versus other loci unknown
  13. 2007 High

    Physical interaction of HMGN1 with ERα and SRF, with estrogen-dependent recruitment to the TFF1 promoter where HMGN1 limits gene activation and H3K9 acetylation, established that transcription factors can recruit HMGN1 to act as a context-dependent transcriptional modulator.

    Evidence Reciprocal co-IP, in vitro pulldown, ChIP for HMGN1 and H3K9ac, knockdown/overexpression, phosphomimetic mutant

    PMID:17938209

    Open questions at the time
    • How HMGN1 simultaneously enhances some acetylation marks and limits others at different promoters not reconciled
    • Genome-wide scope of TF-mediated HMGN1 recruitment unknown
  14. 2010 High

    Genome-wide ChIP-seq revealed that HMGN1 is not randomly distributed but preferentially localizes to DNase I hypersensitive sites, promoters, and functional enhancers, establishing that its chromatin occupancy is targeted to regulatory regions.

    Evidence Genome-wide ChIP-seq for HMGN1 compared to regulatory chromatin marks

    PMID:21173166

    Open questions at the time
    • Mechanism of preferential targeting (sequence vs chromatin features) not resolved
    • Dynamic redistribution upon stimulation not captured
  15. 2012 High

    Discovery that HMGN1 directly stimulates PARP-1 auto-PARylation and interacts with PCNA to enhance its chromatin recruitment at damage sites extended the DNA repair role beyond chromatin accessibility to direct protein–protein facilitation of repair factors.

    Evidence In vitro PARylation with purified proteins, co-IP, laser micro-irradiation imaging of PARP-1 PARylation and PCNA recruitment in Hmgn1-/- cells, deletion mutagenesis

    PMID:22393258 PMID:22736760

    Open questions at the time
    • Whether PARP-1 stimulation and PCNA recruitment are independent or sequential not determined
    • Crystal structure of HMGN1–PCNA complex lacking
  16. 2013 High

    Multi-omic analysis in Hmgn1-/- ESCs showed that HMGN1 preferentially binds CpG island-containing promoters and affects nucleosome positioning at TSSs, DNase I hypersensitivity, and transcription in stem and progenitor cells, linking it to epigenetic regulation of cell identity.

    Evidence Hmgn1-/- ESCs with ChIP-seq, MNase-seq, DNase-seq, RNA-seq

    PMID:23775126

    Open questions at the time
    • Whether nucleosome positioning changes are a direct structural consequence of HMGN1 binding or indirect unknown
    • Functional consequence for differentiation potential quantitatively undefined
  17. 2014 High

    HMGN1 overexpression (modeling chr21 trisomy) was shown to suppress H3K27me3 at bivalent genes and promote B-ALL, establishing HMGN1 as a dosage-sensitive oncogene whose overexpression derepresses PRC2 targets.

    Evidence Mouse trisomy model, HMGN1 overexpression in B cells, ChIP for H3K27me3, B-ALL transplantation

    PMID:24747640

    Open questions at the time
    • Whether HMGN1 directly antagonizes PRC2 binding or acts indirectly through acetylation not resolved
    • Relevance to human B-ALL beyond Down syndrome not established
  18. 2017 High

    In vitro reconstitution showed HMGN1/HMGN2 counteract H1-dependent higher-order chromatin folding without displacing H1, by altering H1 C-terminal domain condensation and redirecting core histone tails inward, clarifying the non-competitive mechanism of chromatin decompaction.

    Evidence Sedimentation assay, hydroxyl radical footprinting, histone tail accessibility assays on reconstituted chromatin

    PMID:28973435

    Open questions at the time
    • Whether this mechanism operates at all genomic loci or preferentially at regulatory elements not tested in vivo
  19. 2018 High

    Spike-in normalized ChIP-seq demonstrated that HMGN1 overexpression causes a global (not locus-specific) increase in H3K27 acetylation, resolving whether the transcriptional amplification effect is quantitative and genome-wide.

    Evidence ChIP-Rx for H3K27ac with exogenous spike-in, HMGN1 overexpression and knockdown in DS B cell models

    PMID:30428356

    Open questions at the time
    • Which HATs mediate the global H3K27ac increase not identified
    • Whether global acetylation increase is direct or secondary to H3K27me3 loss unclear
  20. 2020 High

    Human HMGN1/HMGN2 KO cells showed no defect in transcription-coupled NER, and HMGN1 was not recruited to UV damage sites in human cells, establishing a species-specific difference from the mouse NER phenotype.

    Evidence HMGN1/HMGN2 KO human cells, UV/Illudin S survival, transcription restart, GFP-HMGN1 live imaging, co-IP with TC-NER factors

    PMID:32152397

    Open questions at the time
    • Whether global NER (as opposed to TC-NER) is affected in human cells not fully tested
    • Molecular basis for species difference not identified
  21. 2021 High

    NMR of semi-synthesized HMGN1 with site-specific PTMs revealed that NBD phosphorylation reduces helical propensity and disrupts the nucleosome acidic patch interface, providing the first atomic-level explanation for how phosphorylation abolishes nucleosome binding.

    Evidence Protein semi-synthesis, segmental isotope labeling, NMR, CD, nucleosome binding assays

    PMID:34458797

    Open questions at the time
    • Full high-resolution structure of HMGN1 bound to nucleosome not available
    • How long-range conformational effects of terminal PTMs propagate structurally is incompletely understood
  22. 2025 High

    CRISPR-activation screening identified HMGN1 as the causal chr21 gene for atrioventricular canal defects in Down syndrome; reducing HMGN1 dosage from trisomic levels rescued valvuloseptal defects and restored cardiomyocyte transcriptional identity, establishing HMGN1 as a dosage-sensitive driver of congenital heart disease.

    Evidence Human iPSC and mouse trisomy 21 models, scRNA-seq, CROP-seq CRISPRa screen, allelic HMGN1 deletion/rescue

    PMID:41125893

    Open questions at the time
    • Downstream chromatin targets mediating the cardiac phenotype not fully defined
    • Whether HMGN1 dosage sensitivity operates through H3K27me3 or H3K27ac changes in cardiomyocytes not resolved
  23. 2025 High

    HMGN1 and HMGN2 preferentially bind nucleosomes containing acetylated H3 tails and H2A.Z, yet reduce p300-mediated acetylation of H3K18/K23/K27 on nucleosomes in vitro; double KO mESCs show elevated H3K27me2/me3, revealing a nuanced dual role in both reading and constraining acetylation.

    Evidence Nucleosome binding assays with modified/variant nucleosomes, in vitro p300 acetylation, epiproteomic MS, Hmgn1/Hmgn2 DKO mESCs

    PMID:41325801

    Open questions at the time
    • How HMGN1 simultaneously enhances PCAF-mediated H3K14ac but reduces p300-mediated H3K18/K23/K27ac is mechanistically unresolved
    • Whether preferential binding to acetylated nucleosomes is cause or consequence of acetylation state unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) the full atomic structure of HMGN1 bound to a nucleosome, (2) how HMGN1 is targeted to specific regulatory regions rather than binding all nucleosomes, (3) reconciliation of its apparently opposing effects on different histone acetylation marks (enhancing H3K14ac via PCAF while reducing H3K18/K23/K27ac via p300), and (4) the molecular basis for species-specific differences in its DNA repair functions.
  • No high-resolution cryo-EM or crystal structure of HMGN1–nucleosome complex
  • Targeting mechanism to specific loci unresolved
  • Opposing acetylation effects for different HATs mechanistically unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 8 GO:0098772 molecular function regulator activity 6 GO:0005198 structural molecule activity 2
Localization
GO:0000228 nuclear chromosome 4 GO:0005634 nucleus 2 GO:0005654 nucleoplasm 2
Pathway
R-HSA-4839726 Chromatin organization 8 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1640170 Cell Cycle 3 R-HSA-73894 DNA Repair 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1643685 Disease 2
Partners
EP300ESR1PARP1PCAFPCNASRFYWHAB

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1980 HMG-14 (HMGN1) binds specifically to nucleosome core particles; two molecules bind tightly but reversibly per core particle with higher affinity than for histone-free DNA; nucleosome-HMG complexes are enriched in transcriptionally active gene sequences (beta-globin). Thermal denaturation, nuclease digestion, nucleosome reconstitution, and gene-sequence enrichment assay Nucleic acids research High 6449690
1980 HMG-14 is intrinsically disordered in free solution and binds DNA primarily through its N-terminal half, with the interaction disrupted at 0.3 M NaCl (the same ionic strength used to extract the protein from chromatin). 270-MHz NMR, circular dichroism European journal of biochemistry High 6257511
1994 HMG-14 (HMGN1) footprints on nucleosome cores and chromatosomes map to positions ~25 bp from the DNA ends and near the nucleosomal dyad axis; two HMG-14 molecules bridge two adjacent DNA strands on the nucleosome surface, with binding sites overlapping those of linker histones near the dyad. Hydroxyl radical footprinting of HMG-14 on nucleosome cores and chromatosomes Journal of molecular biology High 8107104
1994 HMG-14 (HMGN1) stimulates RNA polymerase II elongation rate on chromatin templates but not on naked DNA templates, and does not affect initiation of transcription. In vitro transcription assay on in vivo-assembled chromatin vs. DNA templates Science (New York, N.Y.) High 8047885
1994 Upon mitogenic stimulation, HMG-14 (HMGN1) — but not HMG-17 — is serine-phosphorylated in its basic N-terminal region; mononucleosome-associated HMG-14 carries a mitogen-activated kinase that phosphorylates HMG-14 in vitro at the same sites as in intact cells. In vivo labeling, micrococcal nuclease fractionation to mononucleosomes, in vitro kinase assay The EMBO journal High 7925294
1994 Single point mutations in the nucleosomal binding domain (NBD) of HMG-14 at positions A21P or K26C reduce cooperative binding to nucleosome cores 6.7- and 3-fold respectively, demonstrating that the NBD conformation is critical for nucleosome interaction. Site-directed mutagenesis, nucleosome core mobility-shift assay Nucleic acids research High 7971283
1997 The acidic C-terminal region of HMG-14 (HMGN1) alleviates histone H1-mediated transcriptional repression and partially disrupts H1-dependent chromatin compaction; transcriptional and chromatin-unfolding activities are maintained when the C-terminal fragment is replaced by acidic regions from GAL4 or HMG-2. In vitro transcription on SV40 minichromosomes, chromatin compaction assay, domain-swap mutagenesis Molecular and cellular biology High 9315642
1998 The N-terminal domain of HMG-14 contacts histone H2B, while the C-terminal chromatin-unfolding domain contacts the N-terminal tail of histone H3 in nucleosome cores, as determined by protein photocrosslinking. Protein photocrosslinking in nucleosome cores Proceedings of the National Academy of Sciences of the United States of America High 9576905
1998 HMG-14 and HMG-17 (HMGN1/HMGN2) are released from chromatin during mitosis (absent from metaphase/anaphase chromosomes), re-associate with DNA in late telophase, and are actively imported into the nucleus via a bipartite nuclear localization signal requiring importin alpha and energy. Immunofluorescence cell-cycle staging, reconstituted nuclei import assay, permeabilized cells, energy/importin depletion The Journal of cell biology High 9852141
2000 The histone acetyltransferase p300 acetylates HMG-14 (HMGN1) at 7 sites, including 3 within the nucleosomal binding domain and 4 near bipartite nuclear localization domains; acetylation of the NBD by p300 weakens HMG-14 interaction with nucleosome cores. In vitro acetylation by p300, identification of acetylation sites, nucleosome binding assay with acetylated vs. unacetylated protein 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 isotypes; this is a phosphorylation-dependent (not charge-dependent) effect. Immunofluorescence, in vitro nuclear import with wild-type and NBD-phosphomimetic/mutant proteins, affinity chromatography with nuclear extracts from logarithmic vs. mitotic cells Molecular and cellular biology High 12215538
2003 MSK1 and MSK2 are the major kinases responsible for phosphorylation of HMG-14 (HMGN1) in response to mitogenic and stress stimuli; phosphorylation is severely reduced or abolished in MSK1/MSK2 double-knockout mouse fibroblasts. Genetic knockout (MSK1-/-, MSK2-/- mice), in vivo phosphorylation assay, comparison with Coffin-Lowry (RSK2-deficient) cells The EMBO journal High 12773393
2003 HMGN1 enhances the rate of nucleotide excision repair (NER) of UV-induced photoproducts in chromatin by reducing chromatin compaction, thereby increasing accessibility to damaged DNA; Hmgn1-/- MEFs are UV hypersensitive and show slower photoproduct removal; rescue requires nucleosome-binding-competent HMGN1. Hmgn1-/- mouse embryonic fibroblasts, UV survival, slot-blot photoproduct removal assay, host cell reactivation, transfection with wild-type vs. chromatin-binding-deficient mutants The EMBO journal High 12660172
2004 HMGN1 reduces the steady-state levels and rate of stress-induced phosphorylation of histone H3 Ser10 by impeding kinase access to nucleosomal (but not free) H3; stress-induced phosphorylation of HMGN1 transiently weakens its chromatin binding, enabling improved kinase access to H3. Hmgn1-/- MEFs, in vitro kinase assay on nucleosomal vs. free H3, anisomycin treatment kinetics, chromatin fractionation Molecular cell High 15327773
2005 HMGN1 enhances acetylation of histone H3 lysine 14 (H3K14ac) in vivo; in vitro, HMGN1 enhances the ability of the HAT PCAF to acetylate nucleosomal H3 but not free H3; this requires chromatin-binding-competent HMGN1. Hmgn1-/- MEFs, re-expression of wild-type vs. chromatin-binding mutant HMGN1, in vitro PCAF acetylation assay on nucleosomes vs. free H3 The EMBO journal High 16096646
2005 HMGN1 loss increases sensitivity to ionizing radiation and disrupts G2/M checkpoint activation in fibroblasts; rescue requires nucleosome-binding-competent HMGN1, placing chromatin binding as essential for DNA damage checkpoint function. Hmgn1-/- mouse fibroblasts, IR sensitivity, G2/M checkpoint assay, rescue with wild-type vs. NBD-mutant HMGN1 Cancer research High 16061652
2005 HMGN1 acts as a negative regulator of N-cadherin expression in mouse embryonic fibroblasts; loss of HMGN1 increases N-cadherin levels and alters cell adhesion, motility, and aggregation; rescue requires chromatin-binding-competent HMGN1. Hmgn1-/- MEFs, DNA microarray, RT-PCR, western blot, re-expression with wild-type vs. chromatin-binding mutant The FEBS journal Medium 16279949
2006 HMGN1 modulates phosphorylation of histone H2A serine 1; in Hmgn1-/- cells, H2AS1ph is elevated throughout the cell cycle; in vitro, HMGN1 reduces Rsk2- and Msk1-mediated phosphorylation of nucleosomal (but not free) H2A, and HMGN2 shows the same effect. Hmgn1-/- cells, in vitro kinase assay (Rsk2, Msk1) on nucleosomal vs. free H2A, chromatin-binding mutant HMGN1 Biochemistry High 17154547
2006 During embryogenesis, HMGN1 binds Sox9 chromatin in cells poised to express Sox9; loss of HMGN1 accelerates chondrogenic differentiation and elevates HMGN2 occupancy at Sox9; wild-type but not chromatin-binding-deficient HMGN1 rescues the effect on Sox9 expression. Hmgn1-/- limb bud micromass cultures, ChIP, re-expression with wild-type vs. mutant HMGN1 Molecular and cellular biology High 16382150
2007 HMGN1 physically interacts with estrogen receptor alpha (ERα) and serum response factor (SRF) both in vitro and in vivo; at the TFF1 promoter, ERα recruits HMGN1 upon estrogen treatment; HMGN1 limits estrogen-induced gene activation and reduces H3K9 acetylation at target promoters. Co-IP in vivo and in vitro pulldown, knockdown and overexpression, ChIP for HMGN1 and H3K9ac, phosphomimetic mutant HMGN1 Molecular and cellular biology High 17938209
2008 HMGN1 enhances heat shock-induced remodeling of Hsp70 chromatin by promoting H3K14 acetylation at the Hsp70 promoter; HDAC inhibitors abrogate the HMGN1 effect, placing H3K14 acetylation downstream of HMGN1 in this pathway. Hmgn1-/- and +/+ fibroblasts, RT-PCR for Hsp70 transcripts, ChIP for H3K14ac at Hsp70 promoter, HDAC inhibitor treatment The Journal of biological chemistry High 18218636
2010 HMGN1 is not randomly distributed across the genome but preferentially localizes to DNase I hypersensitive sites, promoters, functional enhancers, and transcription factor binding sites. Genome-wide ChIP-seq for HMGN1 compared to regulatory chromatin marks Molecular and cellular biology High 21173166
2011 HMGN1 acts as a negative regulator of MeCP2 expression; alterations in HMGN1 levels change chromatin structure and histone modifications at the MeCP2 promoter; both overexpression and loss of HMGN1 alter mouse behavior. Hmgn1 overexpressor and KO mice, quantitative PCR, western blot, ChIP for histone modifications at MeCP2 promoter, behavioral assays The Journal of biological chemistry High 22009741
2012 HMGN1 stimulates PARP-1 self-PARylation; HMGN1 and PARP-1 interact directly in binding assays; purified HMGN1 stimulates purified PARP-1 self-PARylation in vitro; loss of HMGN1 reduces PARylation at laser-induced DNA damage sites in cells. Hmgn1-/- and +/+ cells, co-immunoprecipitation, in vitro PARylation assay with purified proteins, laser micro-irradiation imaging The Journal of biological chemistry High 22736760
2012 HMGN1 interacts with PCNA and enhances PCNA binding to chromatin (but not to purified DNA); two tetrapeptides in the conserved domain of HMGN1 are required for this interaction; loss of HMGN1 decreases PCNA recruitment to UV-damaged DNA sites. Co-IP/pulldown assay, deletion mutagenesis, live-cell imaging of PCNA recruitment after laser-induced damage, chromatin vs. DNA binding assay Molecular and cellular biology High 22393258
2013 HMGN1 preferentially binds CpG island-containing promoters and affects nucleosome organization at transcription start sites (including an unstable nucleosome), DNase I hypersensitivity genome-wide, and the transcriptional profile of embryonic stem cells and neural progenitors. Hmgn1-/- ESCs, ChIP-seq, MNase-seq for nucleosome positioning, DNase-seq, RNA-seq Molecular and cellular biology High 23775126
2014 HMGN1 overexpression (from chr21q22 triplication) suppresses H3K27 trimethylation in progenitor B cells and promotes B cell proliferation and B-ALL in vivo; bivalent genes marked by H3K27me3 are preferentially derepressed by HMGN1 overexpression. Mouse trisomy model, HMGN1 overexpression in B cells, ChIP for H3K27me3, B-ALL transplantation model Nature genetics High 24747640
2017 HMGN1 and HMGN2 counteract linker histone H1-dependent stabilization of higher-order chromatin structures without displacing H1; they do not disturb H1 globular domain contacts with nucleosomal DNA but alter condensation of the H1 C-terminal domain and redirect core histone tails to more interior positions on the nucleosome. In vitro reconstitution, sedimentation assay, hydroxyl radical footprinting, histone tail accessibility assays Nucleic acids research High 28973435
2018 HMGN1 overexpression globally amplifies transcription and causes a global increase in H3K27 acetylation as revealed by exogenous spike-in normalized ChIP-seq; HMGN1 is necessary for B cell phenotypes in DS trisomy models. Spike-in normalized RNA-seq and ChIP-Rx for H3K27ac, HMGN1 overexpression and knockdown in DS B cell models Cell reports High 30428356
2021 Phosphorylation of serines in the nucleosomal binding domain of HMGN1 decreases helical propensity of the NBD and disrupts its interaction with the nucleosome acidic patch, as shown by NMR spectroscopy; PTMs in N- or C-termini cause conformational perturbations up to 50-60 residues distant from the modification site. Protein semi-synthesis with site-specific PTMs, segmental isotope labeling, NMR spectroscopy, circular dichroism, nucleosome binding assays RSC chemical biology High 34458797
2024 Phosphorylation of the HMGN1 NBD decreases helical propensity and disrupts the interface with the nucleosome acidic patch as shown by NMR spectroscopy and circular dichroism, providing atomic-level detail of how phosphorylation reduces nucleosome binding. NMR spectroscopy, circular dichroism, AlphaFold3 modelling of HMGN1-nucleosome interface Chembiochem : a European journal of chemical biology High 39186607
2025 HMGN1 upregulation in trisomy 21 shifts AVC cardiomyocytes toward a ventricular cardiomyocyte transcriptional state; CRISPR-activation screen identified HMGN1 as the causal chr21 gene; reducing HMGN1 dosage from trisomic levels restores normal AVC gene expression and rescues valvuloseptal defects in a mouse trisomy 21 model. Human iPSC and mouse trisomy 21 models, single-cell RNA-seq, CROP-seq CRISPR-activation screen, allelic HMGN1 deletion/rescue Nature High 41125893
2025 HMGN1 (and HMGN2) function in activation of transcription initiation at over a thousand specific promoters and enhancers; they have shared and unique target genes; HMGN null cells generated by simultaneous deletion of multiple HMGN genes show preferential downregulation of target genes. HMGN null human cell line generation, isogenic rescue lines, genome-wide RNA-seq bioRxivpreprint Medium
2025 HMGN1 and HMGN2 preferentially bind nucleosomes containing acetylated H3 tail residues and the histone variant H2A.Z; in vitro, HMGN1 and HMGN2 binding to nucleosomes reduces p300-mediated acetylation of H3K18, H3K23, and H3K27; Hmgn1/Hmgn2 double KO mESCs show increased H3K27me2 and H3K27me3. Nucleosome binding assays with modified and variant nucleosomes, in vitro p300 acetylation assay, epiproteomic mass spectrometry, Hmgn1-/-, Hmgn2-/-, and double KO mESCs The Journal of biological chemistry High 41325801
2024 HMGN1 binds HBV cccDNA in the nucleus; silencing HMGN1 increases CLK2 kinase-mediated H3 phosphorylation and reduces cccDNA accessibility; HMGN1 promotes HBV transcription and replication through its nucleosomal binding domain. Biotin-avidin enrichment, ChIP, fluorescent in situ hybridization, HMGN1 knockdown and mutant transfection in HBV-infected cells, in vivo HBV mouse model Antiviral research Medium 38181856
2020 In human cells, HMGN1 (alone or combined with HMGN2 knockout) is not required for transcription-coupled nucleotide excision repair (TC-NER); HMGN1 is not recruited to UV-induced DNA damage sites and does not associate with the TC-NER complex; this contrasts with findings in mouse cells. HMGN1/HMGN2 KO and knockdown human cells, UV/Illudin S survival, transcription restart assay, GFP-HMGN1 live-cell recruitment at UV damage, co-IP with TC-NER factors Scientific reports High 32152397

Source papers

Stage 0 corpus · 93 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 53 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
2010 Genomic profiling of HMGN1 reveals an association with chromatin at regulatory regions. Molecular and cellular biology 43 21173166
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 42 22009741
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
2019 Combining Rapid Data Independent Acquisition and CRISPR Gene Deletion for Studying Potential Protein Functions: A Case of HMGN1. Proteomics 38 30901150
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
2012 HMGN1 protein regulates poly(ADP-ribose) polymerase-1 (PARP-1) self-PARylation in mouse fibroblasts. The Journal of biological chemistry 35 22736760
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
2018 HMGN1 and R848 Synergistically Activate Dendritic Cells Using Multiple Signaling Pathways. Frontiers in immunology 34 30619338
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
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
2021 A TNFR2 antibody by countering immunosuppression cooperates with HMGN1 and R848 immune stimulants to inhibit murine colon cancer. International immunopharmacology 27 34794079
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 26 26445971
2006 A role for chromosomal protein HMGN1 in corneal maturation. Differentiation; research in biological diversity 26 16466397
2008 Chromosomal protein HMGN1 enhances the heat shock-induced remodeling of Hsp70 chromatin. The Journal of biological chemistry 25 18218636
1986 Chromosomal proteins HMG-14 and HMG-17. Distinct multigene families coding for similar types of transcripts. The Journal of biological chemistry 25 3782108
2023 Acteoside alleviates UUO-induced inflammation and fibrosis by regulating the HMGN1/TLR4/TREM1 signaling pathway. PeerJ 24 36691481
2007 HMGN1 modulates estrogen-mediated transcriptional activation through interactions with specific DNA-binding transcription factors. Molecular and cellular biology 23 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
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
2021 HMGN1 plays a significant role in CRLF2 driven Down Syndrome leukemia and provides a potential therapeutic target in this high-risk cohort. Oncogene 19 34857887
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
2018 IGF-1R Inhibitor Ameliorates Diabetic Nephropathy with Suppressed HMGN1/TLR4 Pathway. Endocrine, metabolic & immune disorders drug targets 13 29384065
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
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 11 38409569
2021 Site-specific modification and segmental isotope labelling of HMGN1 reveals long-range conformational perturbations caused by posttranslational modifications. RSC chemical biology 11 34458797
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
2022 Shaking up the silence: consequences of HMGN1 antagonizing PRC2 in the Down syndrome brain. Epigenetics & chromatin 9 36463299
2023 Gain of chromosome 21 increases the propensity for P2RY8::CRLF2 acute lymphoblastic leukemia via increased HMGN1 expression. Frontiers in oncology 8 37483494
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 5 38181856
2006 HMGN1 is dispensable for myogenesis and adipogenesis. Gene 4 16451822
2003 The in vitro reconstitution of nucleosome and its binding patterns with HMG1/2 and HMG14/17 proteins. Cell research 4 14672558
2025 Myocardial reprogramming by HMGN1 underlies heart defects in trisomy 21. Nature 3 41125893
2024 KAT7/HMGN1 signaling epigenetically induces tyrosine phosphorylation-regulated kinase 1A expression to ameliorate insulin resistance in Alzheimer's disease. World journal of psychiatry 3 38617985
2024 HMGN1 loss sensitizes lung cancer cells to chemotherapy. Scientific reports 2 38710740
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 Anti-TNFR2 antibody and HMGN1 combined with TIL cell therapy inhibits colorectal cancer progression by enhancing immune response. Biochemical and biophysical research communications 1 40483876
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
2025 Identification of a Novel RUNX1::HMGN1 Fusion in Therapy Acute Myeloid Leukemia. Molecular carcinogenesis 0 41252680
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 0 41325801
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
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