Affinage

HMGB2

High mobility group protein B2 · UniProt P26583

Length
209 aa
Mass
24.0 kDa
Annotated
2026-04-28
100 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HMGB2 is a non-histone chromatin architectural protein that bends and unwinds DNA through its tandem HMG box domains—box B being the principal domain for DNA recognition and conformational change—thereby facilitating assembly of diverse nucleoprotein complexes and modulating transcription (PMID:628842, PMID:9888798, PMID:8339930). It acts as a transcriptional co-regulator by enhancing transcription factor binding at target promoters (Oct-1 at GFI1B, NF-Y at topo IIα, Lef-1/β-catenin at Wnt targets, C/EBPβ during adipogenesis, SRC-1/ER in endocrine-resistant breast cancer), and its acetylation enables nucleosome binding and cooperative chromatin remodeling with SWI/SNF (PMID:19965638, PMID:19805379, PMID:19223331, PMID:34215724, PMID:25284587, PMID:19522541). During cellular senescence, HMGB2 prevents heterochromatin spreading into SASP gene loci and its nuclear depletion triggers CTCF spatial clustering and 3D genome reorganization; in CD8+ T cells it functions as a cell-intrinsic epigenetic regulator required for stem-like progenitor exhausted T cell maintenance during chronic infection and cancer (PMID:27799366, PMID:29706538, PMID:37704621). Hmgb2-knockout mice exhibit reduced male fertility with spermatogenic defects, accelerated osteoarthritis with superficial-zone chondrocyte apoptosis, and impaired muscle regeneration, establishing essential tissue-specific roles in germ cell differentiation, cartilage homeostasis, and myogenesis (PMID:11262228, PMID:19139395, PMID:27672022).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1978 High

    Establishing that HMG proteins alter DNA topology resolved a fundamental question about whether non-histone chromosomal proteins could directly modify DNA structure, opening the field of HMG-mediated chromatin architecture.

    Evidence Topological winding number assay showing HMG1/2 reduce linking number of circular DNA

    PMID:628842

    Open questions at the time
    • Mechanism of unwinding (intercalation vs. bending) not yet resolved
    • No domain dissection performed
  2. 1979 High

    Quantifying unwinding angles (~26° per HMG2 molecule) and demonstrating preferential single-strand binding established that HMG proteins locally denature base pairs rather than merely wrapping DNA.

    Evidence Melting absorption technique and competition unwinding experiments

    PMID:226939

    Open questions at the time
    • Whether unwinding reflects physiological function or is an in vitro artifact was unresolved
    • Individual domain contributions unknown
  3. 1993 High

    Demonstrating that HMG1/2 bend DNA into circles as small as 59–66 bp and that box B suffices for bending established the paradigm that HMGB proteins function as architectural facilitators of nucleoprotein complex assembly.

    Evidence Ligase-mediated circularization assay, invertasome assembly assay with domain dissection

    PMID:8339930

    Open questions at the time
    • Box A function remained unclear
    • In vivo relevance of DNA bending not yet shown
  4. 1994 High

    Discovery that HMG2 acts as a basal repressor of RNA Pol II transcription—blocking elongation after pre-initiation complex formation—and that TFIIH counteracts this repression revealed a dual transcriptional regulatory role.

    Evidence Reconstituted in vitro transcription with order-of-addition and antibody depletion experiments

    PMID:7797075 PMID:8007973

    Open questions at the time
    • Whether repression and activation occur on the same promoters in vivo was unknown
    • Mechanism of TFIIH-mediated relief not fully defined
  5. 1999 High

    Identifying box B as the primary domain for DNA recognition and conformational change—with Phe-102 intercalation being critical—and showing that HMGB2 incorporates into RAG1/2-RSS complexes to enhance V(D)J recombination established two key paradigms: domain specialization and a direct role in adaptive immune receptor assembly.

    Evidence SPR kinetics, mutagenesis, supercoiling assays for domain function; co-IP, EMSA, circular permutation, and in vivo recombination assay for RAG interaction

    PMID:10390537 PMID:10490593 PMID:9888798

    Open questions at the time
    • Structural basis of box B–DNA interaction at atomic resolution not determined
    • Relative contributions of HMGB1 vs HMGB2 in V(D)J recombination in vivo unclear
  6. 2001 High

    Hmgb2-knockout mice revealed essential, non-redundant roles: male infertility with spermatocyte degeneration demonstrated that despite co-expression with HMGB1, HMGB2 has tissue-specific functions in germ cell differentiation.

    Evidence Hmgb2−/− mouse phenotyping with histology and immunostaining

    PMID:11262228

    Open questions at the time
    • Molecular targets of HMGB2 in spermatocytes not identified
    • Whether phenotype reflects chromatin architecture vs. transcription regulation unknown
  7. 2002 High

    Identification of HMGB2 as a SET complex component that provides DNA bending/looping activity and is specifically cleaved by granzyme A linked HMGB2 to the cytotoxic lymphocyte killing pathway and apoptotic DNA fragmentation.

    Evidence Co-immunoprecipitation, confocal colocalization at ER, in vitro granzyme A cleavage assay

    PMID:11909973

    Open questions at the time
    • Whether granzyme A cleavage of HMGB2 is essential for target cell death in vivo not tested
    • Stoichiometry within the SET complex undefined
  8. 2009 High

    A burst of discoveries established HMGB2 as a transcriptional co-activator at specific promoters (GFI1B, topo IIα, Lef-1/β-catenin targets), showed acetylation enables nucleosome binding and SWI/SNF co-remodeling, and revealed essential roles in chondrocyte survival and cartilage homeostasis via Wnt signaling.

    Evidence ChIP at GFI1B promoter with differentiation assay; siRNA/reporter for topo IIα; EMSA/reporter/KO mouse for Lef-1; nucleosome binding/remodeling assays with acetylated HMGB2; Hmgb2−/− mouse osteoarthritis model

    PMID:19139395 PMID:19223331 PMID:19522541 PMID:19805379 PMID:19965638

    Open questions at the time
    • Acetyltransferase(s) responsible for HMGB2 acetylation in vivo not identified
    • Whether nucleosome remodeling function operates at specific loci or genome-wide unknown
    • Direct structural basis for acetylation-dependent nucleosome recognition unresolved
  9. 2016 High

    ChIP-seq and Hi-C revealed that HMGB2 preferentially occupies SASP gene loci during senescence, acting as an anti-silencing boundary that prevents heterochromatin spreading; separately, HMGB2 was shown to drive myogenesis through IGF2BP2-mediated post-transcriptional regulation of Myf5.

    Evidence ChIP-seq/Hi-C with siRNA in senescent fibroblasts; shRNA knockdown with IGF2BP2 rescue and in vivo muscle injury model

    PMID:27672022 PMID:27799366

    Open questions at the time
    • Whether HMGB2 directly recruits boundary factors or passively blocks heterochromatin unknown
    • Mechanism by which HMGB2 transcriptionally activates IGF2BP2 not defined
  10. 2018 High

    Nuclear depletion of HMGB2 was shown to be an early senescence event that triggers CTCF spatial clustering and 3D genome loop reorganization, establishing HMGB2 as a master regulator of genome topology during cellular aging; concurrently, cytoplasmic retention of HMGB2 by lnc-CRCMSL was found to suppress EMT by preventing nuclear HMGB2-OCT4 interaction.

    Evidence Hi-C, single-cell RNA-seq, HMGB2 knockdown/rescue across three cell types; RNA pulldown plus leptomycin B pharmacological validation

    PMID:29706538 PMID:30575817

    Open questions at the time
    • Direct molecular mechanism by which HMGB2 prevents CTCF clustering not defined
    • Whether nucleocytoplasmic shuttling regulation differs across tissue types untested
  11. 2023 High

    Discovery that HMGB2 cell-intrinsically regulates exhausted CD8+ T cell progenitor (Tpex) differentiation during chronic infection and cancer—independently of canonical TCF-1/TOX—revealed a new immune-epigenetic function with therapeutic implications.

    Evidence Hmgb2−/− mouse with chronic LCMV and tumor models, single-cell RNA-seq, ATAC-seq

    PMID:37704621

    Open questions at the time
    • Direct chromatin targets of HMGB2 in Tpex cells not mapped
    • Whether HMGB2 acts through CTCF reorganization in T cells as in senescence untested
  12. 2024 High

    Identification of NAT10-mediated ac4C modification on HMGB2 mRNA CDS that enhances translation via eEF2 recruitment established a novel epitranscriptomic layer controlling HMGB2 protein abundance.

    Evidence acRIP-seq, ribosome profiling, RNA pulldown/mass spectrometry, site-specific mutagenesis

    PMID:39030964

    Open questions at the time
    • Whether ac4C-mediated translational control is tissue-specific unknown
    • Upstream signals regulating NAT10-dependent HMGB2 mRNA modification not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) how HMGB2 mechanistically prevents CTCF clustering and heterochromatin spreading at the molecular level, (2) which acetyltransferases modify HMGB2 in vivo and how this is regulated, (3) whether HMGB2's genome-topology and transcriptional co-activator functions are separable, and (4) the structural basis for promoter-specific recruitment.
  • No high-resolution structure of HMGB2 bound to a nucleosome or promoter complex
  • No genome-wide binding data comparing HMGB2 occupancy across tissues and differentiation states
  • Functional redundancy with HMGB1 incompletely dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 5 GO:0005198 structural molecule activity 3 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 4 GO:0005654 nucleoplasm 2 GO:0005694 chromosome 2 GO:0005829 cytosol 2
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-4839726 Chromatin organization 3 R-HSA-5357801 Programmed Cell Death 2
Partners
CTCFESR1IGF2BP2LEF1OCT4RAG1SETSRC1
Complex memberships
RAG1/RAG2-RSS complexSET complexSRC-1/ER complex

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1978 HMG1 and HMG2 reduce the linking number of circular DNA when present during covalent closure, demonstrating they can unwind the DNA double helix or induce supercoiling. Topological winding number assay with circular DNA Science High 628842
1979 HMG1 and HMG2 unwind the DNA double helix by local denaturation of base pairs; net unwinding angles measured at 22° and 26° per molecule for HMG1 and HMG2 respectively; HMG1 has higher affinity for single-stranded vs. double-stranded DNA. Melting absorption technique, competition unwinding experiments Nucleic acids research High 226939
1993 HMG1 and HMG2 promote assembly of complex nucleoprotein structures by bending DNA extremely efficiently, forming circles as small as 59–66 bp; HMG box B domain of HMG1 is sufficient for DNA bending and invertasome assembly; they can substitute for the prokaryotic HU protein in Hin-mediated site-specific DNA inversion. Invertasome assembly assay, ligase-mediated circularization assay, partial proteolytic digestion domain analysis Genes & development High 8339930
1994 HMG2 acts as a basal repressor of class II gene transcription by inhibiting transcription after assembly of a TBP-TFIIA-promoter complex but before formation of the fourth phosphodiester bond by RNA Pol II; a TFIIH-associated factor counteracts this repression in an ATP-dependent manner. In vitro transcription reconstitution, order-of-addition experiments, antibody depletion, ATP analog inhibition Molecular and cellular biology High 8007973
1995 HMG-2 was identified as a factor necessary for transcriptional activation in a defined in vitro RNA Pol II system; activation requires TFIIA and TAFs within TFIID; HMG-2 stabilizes an activated conformation of the TFIID-TFIIA-promoter complex; TFIIB dissociates more slowly from the activated preinitiation complex. In vitro transcription with purified factors, TFIIB titration, preinitiation complex analysis Genes & development High 7797075
1997 Nuclear accumulation of HMG2 is mediated by basic regions interspaced with the HMG1/2 box DNA-binding sequence acting as a novel nuclear localization signal; retention within the nucleus requires the acidic carboxyl terminus, demonstrated by interspecies heterokaryon assay. HMG2-β-galactosidase fusion protein expression in COS-7 cells, deletion analysis, interspecies heterokaryon assay Biochemistry High 9166769
1998 HMG2 enhances the nuclease activity of DFF40/CAD during apoptosis, suggesting HMG proteins augment DNA fragmentation through changes in chromosome structure. Biochemical identification and in vitro nuclease activity assay with bacterially expressed HMG2 Biochemical and biophysical research communications Medium 9784391
1999 The RAG1 homeodomain directly interacts with both HMG boxes of HMG1 and HMG2; this interaction facilitates RAG1/RAG2 binding to the recombination signal sequence, mainly by promoting high-affinity binding to the nonamer motif; HMG1/2 significantly enhance binding and bending of the 23RSS; transient HMG1/2 overexpression increases V(D)J recombination in vivo. Co-immunoprecipitation/direct interaction assay, electrophoretic mobility shift assay, circular permutation assay, transfection experiment Molecular and cellular biology High 10490593
1999 A dimer of RAG1 stably incorporates HMG2 into the RAG1-RSS complex; HMG2 can increase the affinity of RAG1 for the RSS in the absence of RAG2. Electrophoretic mobility shift assay, recombinant protein expression, zinc analysis Nucleic acids research Medium 10390537
1999 HMG2 box B is the main domain for DNA recognition and conformational changes (preferential binding to negatively supercoiled DNA, DNA unwinding); box A does not possess these activities alone; Phe-102 in box B intercalates into the base stack whereas Ala-16 in box A cannot. Gel retardation, DNA supercoiling assay, surface plasmon resonance (SPR) binding kinetics, computer modeling, recombinant peptide expression Biochemistry High 9888798
2001 HMGB1 physically interacts with p73α and p73β (both splice variants); both HMG box domains A and B of HMGB1 interact with p73α; HMGB1 enhances binding of p73 to specific cognate DNA sites; endogenous HMGB1 and HMGB2 inhibit p73α/β- and p53-dependent transactivation from the Bax gene promoter in a cell- and promoter-specific manner. Pull-down assay, gel-shift assay, transient transfection with antisense strategy, reporter gene assay The Journal of biological chemistry High 11748232
2001 Male Hmgb2-/- mice have reduced fertility with Sertoli and germ cell degeneration in seminiferous tubules and immotile spermatozoa; HMGB2 is expressed at very high levels in primary spermatocytes but barely detectable in spermatogonia and elongated spermatids, indicating a specialized role in germ cell differentiation. Knockout mouse (Hmgb2-/-) phenotypic analysis, histology, immunostaining, expression analysis Development High 11262228
2002 HMG2 is a component of the SET complex (endoplasmic reticulum-associated ~270-420 kDa complex containing SET, pp32, and APE); HMG2 coprecipitates with SET; cytoplasmic HMG2 colocalizes with SET at the ER; HMG2 provides the DNA bending and looping activities of the SET complex; HMG2 (but not HMG1) is a substrate of granzyme A, which cleaves after Lys65 in HMG box A, destroying DNA binding and bending functions. Co-immunoprecipitation, confocal microscopy colocalization, in vitro granzyme A cleavage assay Molecular and cellular biology High 11909973
2003 HMGB1 and HMGB2 are present in two forms in mitotic cells—free and associated with condensed chromatin—that rapidly exchange; for HMGB2, two sites encompassing HMG-box A and B are responsible for binding to mitotic chromosomes; this interaction is rapidly inactivated by cell permeabilization or chemical fixation. Live-cell imaging with GFP/DsRed-tagged proteins, fluorescence recovery after photobleaching (FRAP) Molecular biology of the cell High 12925773
2005 Isolated HMG box A from HMGB2 binds DNA in two modes: a flexible hinge mode at low protein concentrations (inducing average DNA bend of 114° at 50 mM Na+ or 87° at 100 mM Na+ and increasing DNA contour length) and a cooperative filament mode at higher concentrations. Optical tweezers single-molecule DNA stretching assay Biophysical journal High 15833996
2009 HMGB2 is uniquely expressed in the superficial zone (SZ) of articular cartilage; aging-related loss of HMGB2 leads to increased chondrocyte apoptosis and earlier onset of more severe osteoarthritis in Hmgb2-/- mice; HMGB2 supports chondrocyte survival. Hmgb2-/- knockout mouse analysis, immunohistochemistry, in vitro apoptosis induction assay, histological scoring PNAS High 19139395
2009 HMGB2 enhances binding of Lef-1 to its target sequence and potentiates transcriptional activation of the Lef-1/β-catenin complex; the HMG domain of HMGB2 is required for interaction with Lef-1; HMGB2 and Wnt/β-catenin signaling co-localize specifically in the superficial zone of articular cartilage; conditional deletion of β-catenin in chondrocytes induces apoptosis. Luciferase reporter assay, electrophoretic mobility shift assay, immunofluorescence co-localization, conditional knockout mouse PNAS High 19805379
2009 HMGB1 and HMGB2 up-regulate cellular expression of topoisomerase IIα; HMGB2 modulates binding of transcription factor NF-Y to the topo IIα promoter; HMGB1 DNA-bending activity is required for topo IIα promoter activation; this activation is inhibited by pRb. Knockdown of HMGB1/2 (siRNA), reporter assay, RT-PCR, Western blot, ChIP Nucleic acids research High 19223331
2009 Acetylated forms of HMGB1 and HMGB2 acquire the ability to bind core nucleosomal particles (a property absent in non-acetylated proteins); acetylated HMGB1/2 show stronger binding to linker DNA-containing nucleosomes and higher co-remodeling activity with SWI/SNF and RSC; acetylation enhances SWI/SNF binding to the nucleosome without affecting its ATPase activity. Nucleosome binding assay, SWI/SNF/RSC-dependent nucleosome mobilization assay, ATPase activity measurement Biochemistry High 19522541
2009 HMGB2 regulates erythroid differentiation by binding to the GFI1B promoter in vivo and up-regulating its trans-activation by enhancing binding of Oct-1 and, to a lesser extent, GATA-1 and NF-Y; HMGB2 knockdown in hematopoietic progenitors leads to decreased Gfi-1B expression and impaired erythroid differentiation. ChIP (in vivo promoter binding), electrophoretic mobility shift assay, shRNA knockdown, differentiation assay Blood High 19965638
2011 HMGB2 suppresses chondrogenic differentiation of mesenchymal stem cells; HMGB2 negatively regulates the stimulatory effect of Wnt/β-catenin signaling on the Runx2 proximal promoter; loss of HMGB2 accelerates osteogenesis and chondrogenic hypertrophy (enhanced Col10a1 and Runx2 expression) in MSC. Lentiviral HMGB2 transduction, Hmgb2-/- mouse MSC differentiation assays, reporter assay for Runx2 promoter The Journal of biological chemistry High 21890638
2012 HMGB2 knockdown sensitizes colorectal cancer cells to ionizing radiation by increasing DNA damage and impairing DNA damage repair; p53 directly down-regulates HMGB2 promoter activity (confirmed by luciferase reporter and Nutlin-3/Tet-On p53 induction); radiation downregulates HMGB2 in TP53-intact but not TP53-mutant cells. shRNA knockdown, clonogenic assay, DNA damage markers, luciferase reporter assay, Nutlin-3 treatment, Tet-On p53 induction Cancer biology & therapy High 23255232
2013 Oct4 post-translational modifications (phosphorylation and sumoylation) regulate its interaction with Hmgb2 and the SET complex; this promotes Akt activation and preserves H3K27me3 modifications in daughter progeny to maintain pluripotency in murine embryonic stem cells. Co-immunoprecipitation, phosphorylation mutant analysis, Akt activity assays, chromatin immunoprecipitation (H3K27me3) Stem cells Medium 23495099
2014 HMGB2 interacts with SRC-1 and the oestrogen receptor (ER) in the endocrine-resistant setting; HMGB2/SRC-1/ER complex is enriched at promoter regions of target genes including the RNA helicase DDX18; modulation of DDX18 directly affects growth of tamoxifen-resistant cells. ChIP-seq (HMGB2), co-immunoprecipitation, gene expression integration, siRNA knockdown Oncogene High 25284587
2015 Lrp1-AS (antisense lncRNA) directly binds to HMGB2 and inhibits its activity to enhance Srebp1a-dependent transcription of Lrp1; short oligonucleotides targeting Lrp1-AS inhibit the lncRNA-HMGB2 interaction and increase Lrp1 expression. RNA-protein binding assay, co-immunoprecipitation, reporter assay, oligonucleotide targeting Cell reports High 25937287
2016 HMGB2 preferentially localizes to SASP gene loci during senescence; loss of HMGB2 allows repressive heterochromatin to spread into SASP gene loci, incorporating them into SAHF and blunting SASP gene expression; HMGB2 acts as a master regulator of SASP by preventing heterochromatin spreading. ChIP-seq, siRNA knockdown, Hi-C, immunofluorescence, gene expression analysis The Journal of cell biology High 27799366
2016 HMGB2 is an essential nuclear transcriptional co-regulator in myogenesis; HMGB2 promotes Myf5 and cyclin A2 protein levels (not mRNA) by inducing IGF2BP2, an RNA-binding protein that enhances Myf5 mRNA translation and cyclin A2 mRNA stabilization; HMGB2 depletion in vivo reduces satellite cells and impairs muscle repair. siRNA/shRNA knockdown, overexpression, Western blot, RT-PCR, rescue experiment with IGF2BP2, in vivo muscle injury model Journal of cell science High 27672022
2018 Nuclear depletion of HMGB2 occurs early on the path to senescence and coincides with dramatic spatial clustering of CTCF; HMGB2 knockdown is sufficient to induce senescence-associated CTCF clustering and loop reshuffling; ectopic HMGB2 expression rescues these effects. Hi-C, single-cell transcriptomics, imaging, in silico modeling, HMGB2 knockdown and rescue experiments across three cell types Molecular cell High 29706538
2009 HMGB2 stabilizes p53 in HPV-positive HeLa cells by interfering with E6/E6AP-mediated ubiquitination and degradation of p53; HMGB2 overexpression leads to G1 cell cycle arrest; this effect is specific to HPV-positive cells. Co-expression experiment, ubiquitination assay, siRNA knockdown, FACS cell cycle analysis Cancer letters Medium 20036050
2017 HMGB2 promotes neointimal hyperplasia and VSMC proliferation/migration by inducing reactive oxygen species through increased p47phox phosphorylation; HMGB2-induced effects are mediated via RAGE (receptor for advanced glycation end products) but not TLR4, as RAGE knockdown/deficiency but not TLR4 knockdown abolished HMGB2 effects. Hmgb2-/- mouse arterial injury model, perivascular HMGB2 administration, siRNA knockdown of p47phox and RAGE/TLR4, ROS measurement Arteriosclerosis, thrombosis, and vascular biology High 28183701
2018 HMGB2 promotes myocardial ischemic injury by stimulating ROS production via RAGE signaling, thereby aggravating cell apoptosis, inflammation, and autophagosome clearance impairment; RAGE knockdown abolishes HMGB2-induced effects. Intramyocardial injection of HMGB2 in MI rat model, NADPH oxidase inhibitor (apocynin) co-administration, RAGE knockdown American journal of physiology. Heart and circulatory physiology Medium 28011583
2018 Hmgb2-/- mice show cardiac dysfunction due to AKT inactivation and decreased SERCA2a activity; HMGB2 loss worsens pressure overload-induced heart failure after TAC surgery, indicating HMGB2 plays a cardioprotective role via AKT/SERCA2a pathway. Hmgb2-/- knockout mouse, TAC surgery model, Western blot for AKT activation and SERCA2a activity, echocardiography Circulation journal Medium 30487376
2018 HMGB2 mediates adipogenesis by enhancing expression of C/EBPβ through direct binding to the 'GGGTCTCAC' sequence in its promoter specifically during the mitotic clonal expansion stage; exogenous C/EBPβ rescues adipogenic defects caused by HMGB2 inhibition. ChIP assay (HMGB2 binding to C/EBPβ promoter), Hmgb2-/- mouse, promoter reporter assay, rescue experiment Cell death & disease High 34215724
2019 HMGB2 is a transcriptional suppressor of latexin in hematopoietic stem cells; HMGB2 identified by DNA pull-down and mass spectrometry as binding the latexin promoter; HMGB2 knockdown increases latexin expression and decreases HSC number and regeneration; a functional SNP (rs31528793) in the latexin promoter affects HMGB2 binding and promoter activity. DNA pull-down followed by mass spectrometry, ChIP, siRNA knockdown, in vivo HSC number and regeneration assay, SNP promoter assay Haematologica High 31171637
2019 HMGB2 is a negative regulator of telomerase activity in human embryonic stem cells and neuroectodermal progenitors; HMGB2 deficiency activates PI3K/AKT/GSK-3β/β-catenin signaling and augments TERT/TERC transcription; HMGB2 and HMGB1 have opposing roles in telomerase regulation. shRNA-mediated knockdown in stably transfected hESCs, telomerase activity assay, RT-PCR, Western blot, TERRA measurement FASEB journal Medium 31661640
2018 lnc-CRCMSL physically binds to HMGB2 (identified by RNA pulldown) and stabilizes HMGB2 in the cytoplasm; lnc-CRCMSL knockdown shifts HMGB2 to the nucleus where it triggers EMT programming by interacting with OCT4; nuclear export inhibitor (leptomycin B) counteracts lnc-CRCMSL-mediated suppression of EMT, confirming that cytoplasmic retention of HMGB2 is the key mechanism. RNA pulldown, subcellular fractionation, co-immunoprecipitation (HMGB2-OCT4), leptomycin B treatment, in vivo tumor model Oncogene High 30575817
2023 HMGB2 regulates the differentiation and maintenance of stem-like progenitor exhausted CD8+ T cells (Tpex) during chronic viral infection and cancer through epigenetic and transcriptional programming; HMGB2 acts cell-intrinsically—despite Hmgb2-/- CD8+ T cells expressing TCF-1 and TOX, these master regulators cannot sustain Tpex differentiation. Hmgb2-/- mouse, chronic LCMV infection model, tumor model, single-cell transcriptomics, ATAC-seq epigenetic profiling Nature communications High 37704621
2024 NAT10-mediated N4-acetylcytidine (ac4C) modification within the coding sequence of HMGB2 mRNA enhances HMGB2 translation by facilitating eukaryotic elongation factor 2 (eEF2) binding to the ac4C sites. Acetylated RNA immunoprecipitation sequencing (acRIP-seq), ribosome profiling, RNA immunoprecipitation, RNA pull-down, mass spectrometry, site-specific mutation analysis Cancer communications High 39030964
2022 HMGB2 is predominantly expressed in the outer nuclear layer of the retina and is released to the cytoplasm after oxidative injury; exogenous HMGB2 reduces Nrf2 and HO-1 expression and activates the NF-κB/NLRP3 pathway; HMGB2 knockdown increases cell viability, up-regulates Nrf2/HO-1, and down-regulates pyroptosis-related proteins in H2O2-treated cells. Mouse light-induced retinal damage model, siRNA knockdown, recombinant HMGB2 protein treatment, Western blot, immunofluorescence Free radical biology & medicine Medium 35091064

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 The nonspecific DNA-binding and -bending proteins HMG1 and HMG2 promote the assembly of complex nucleoprotein structures. Genes & development 309 8339930
1978 Nonhistone proteins HMG1 and HMG2 change the DNA helical structure. Science (New York, N.Y.) 222 628842
2015 miR-23b-3p regulates the chemoresistance of gastric cancer cells by targeting ATG12 and HMGB2. Cell death & disease 190 25996293
2018 HMGB2 Loss upon Senescence Entry Disrupts Genomic Organization and Induces CTCF Clustering across Cell Types. Molecular cell 174 29706538
2001 Reduced fertility and spermatogenesis defects in mice lacking chromosomal protein Hmgb2. Development (Cambridge, England) 172 11262228
2001 HMGB1 and HMGB2 cell-specifically down-regulate the p53- and p73-dependent sequence-specific transactivation from the human Bax gene promoter. The Journal of biological chemistry 164 11748232
2016 HMGB2 orchestrates the chromatin landscape of senescence-associated secretory phenotype gene loci. The Journal of cell biology 137 27799366
1995 Activation of the TFIID-TFIIA complex with HMG-2. Genes & development 131 7797075
2009 Aging-related loss of the chromatin protein HMGB2 in articular cartilage is linked to reduced cellularity and osteoarthritis. Proceedings of the National Academy of Sciences of the United States of America 118 19139395
2002 HMG2 interacts with the nucleosome assembly protein SET and is a target of the cytotoxic T-lymphocyte protease granzyme A. Molecular and cellular biology 118 11909973
1989 Tissue specificity of nucleo-cytoplasmic distribution of HMG1 and HMG2 proteins and their probable functions. European journal of biochemistry 113 2583185
2003 Association of chromatin proteins high mobility group box (HMGB) 1 and HMGB2 with mitotic chromosomes. Molecular biology of the cell 110 12925773
1999 The RAG1 homeodomain recruits HMG1 and HMG2 to facilitate recombination signal sequence binding and to enhance the intrinsic DNA-bending activity of RAG1-RAG2. Molecular and cellular biology 106 10490593
1979 Nonhistone proteins HMG1 and HMG2 unwind DNA double helix. Nucleic acids research 94 226939
2015 Antisense RNA controls LRP1 Sense transcript expression through interaction with a chromatin-associated protein, HMGB2. Cell reports 87 25937287
2018 HMGB2 is associated with malignancy and regulates Warburg effect by targeting LDHB and FBP1 in breast cancer. Cell communication and signaling : CCS 75 29463261
1981 Loss of chromosomal high mobility group proteins HMG1 and HMG2 when mouse neuroblastoma and Friend erythroleukemia cells become committed to differentiation. Proceedings of the National Academy of Sciences of the United States of America 71 6458811
2009 Chromatin protein HMGB2 regulates articular cartilage surface maintenance via beta-catenin pathway. Proceedings of the National Academy of Sciences of the United States of America 69 19805379
1997 Novel autoantigens of perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) in ulcerative colitis: non-histone chromosomal proteins, HMG1 and HMG2. Clinical and experimental immunology 67 9010268
2005 Dual binding modes for an HMG domain from human HMGB2 on DNA. Biophysical journal 61 15833996
1998 Prevalence and characterization of novel pANCA, antibodies to the high mobility group non-histone chromosomal proteins HMG1 and HMG2, in systemic rheumatic diseases. The Journal of rheumatology 61 9558172
1995 Expression of the Arabidopsis HMG2 gene, encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase, is restricted to meristematic and floral tissues. The Plant cell 61 7780305
1999 A dimer of the lymphoid protein RAG1 recognizes the recombination signal sequence and the complex stably incorporates the high mobility group protein HMG2. Nucleic acids research 59 10390537
1990 Primary structure of non-histone chromosomal protein HMG2 revealed by the nucleotide sequence. Biochemistry 59 2350545
2017 Long non-coding RNA MALAT1 drives gastric cancer progression by regulating HMGB2 modulating the miR-1297. Cancer cell international 57 28396617
2023 Structure and Functions of HMGB2 Protein. International journal of molecular sciences 56 37176041
1994 Repression of basal transcription by HMG2 is counteracted by TFIIH-associated factors in an ATP-dependent process. Molecular and cellular biology 56 8007973
2017 Expression of HMGB2 indicates worse survival of patients and is required for the maintenance of Warburg effect in pancreatic cancer. Acta biochimica et biophysica Sinica 52 28069585
2007 Chemical phenotypes of the hmg1 and hmg2 mutants of Arabidopsis demonstrate the in-planta role of HMG-CoA reductase in triterpene biosynthesis. Chemical & pharmaceutical bulletin 50 17917299
1999 High mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 are significant target antigens of perinuclear anti-neutrophil cytoplasmic antibodies in autoimmune hepatitis. Gut 48 10323891
2018 Long noncoding RNA CRCMSL suppresses tumor invasive and metastasis in colorectal carcinoma through nucleocytoplasmic shuttling of HMGB2. Oncogene 47 30575817
2019 The lncRNA HOXA11-AS promotes glioma cell growth and metastasis by targeting miR-130a-5p/HMGB2. European review for medical and pharmacological sciences 46 30657566
1990 Efficient large-scale purification of non-histone chromosomal proteins HMG1 and HMG2 by using Polybuffer-exchanger PBE94. Journal of chromatography 46 2277118
2011 Expression patterns and function of chromatin protein HMGB2 during mesenchymal stem cell differentiation. The Journal of biological chemistry 45 21890638
2012 Positive genetic interactors of HMG2 identify a new set of genetic perturbations for improving sesquiterpene production in Saccharomyces cerevisiae. Microbial cell factories 44 23259547
2010 Observations on squalene accumulation in Saccharomyces cerevisiae due to the manipulation of HMG2 and ERG6. FEMS yeast research 44 20550581
2019 Oncogenic KSHV-encoded interferon regulatory factor upregulates HMGB2 and CMPK1 expression to promote cell invasion by disrupting a complex lncRNA-OIP5-AS1/miR-218-5p network. PLoS pathogens 43 30699189
2009 HMGB1 and HMGB2 proteins up-regulate cellular expression of human topoisomerase IIalpha. Nucleic acids research 41 19223331
2013 Oct4 interaction with Hmgb2 regulates Akt signaling and pluripotency. Stem cells (Dayton, Ohio) 40 23495099
2017 Association of Serum HMGB2 Levels With In-Stent Restenosis: HMGB2 Promotes Neointimal Hyperplasia in Mice With Femoral Artery Injury and Proliferation and Migration of VSMCs. Arteriosclerosis, thrombosis, and vascular biology 38 28183701
2009 Nucleosome binding properties and Co-remodeling activities of native and in vivo acetylated HMGB-1 and HMGB-2 proteins. Biochemistry 38 19522541
2016 Association of serum HMGB2 level with MACE at 1 mo of myocardial infarction: Aggravation of myocardial ischemic injury in rats by HMGB2 via ROS. American journal of physiology. Heart and circulatory physiology 37 28011583
1999 Differences in DNA recognition and conformational change activity between boxes A and B in HMG2 protein. Biochemistry 37 9888798
1998 Identification of the nuclear factor HMG2 as an activator for DFF nuclease activity. Biochemical and biophysical research communications 37 9784391
1992 Structure of a gene coding for human HMG2 protein. The Journal of biological chemistry 37 1551873
2014 Genomic interaction between ER and HMGB2 identifies DDX18 as a novel driver of endocrine resistance in breast cancer cells. Oncogene 35 25284587
2024 Targeting N4-acetylcytidine suppresses hepatocellular carcinoma progression by repressing eEF2-mediated HMGB2 mRNA translation. Cancer communications (London, England) 34 39030964
2023 HMGB2 regulates the differentiation and stemness of exhausted CD8+ T cells during chronic viral infection and cancer. Nature communications 34 37704621
2020 MicroRNA-127-5p impairs function of granulosa cells via HMGB2 gene in premature ovarian insufficiency. Journal of cellular physiology 34 32391592
2012 High-mobility group box 2 (HMGB2) modulates radioresponse and is downregulated by p53 in colorectal cancer cell. Cancer biology & therapy 34 23255232
2010 Nucleocytoplasmic distribution of the Arabidopsis chromatin-associated HMGB2/3 and HMGB4 proteins. Plant physiology 34 20940346
1977 Interaction of non-histone chromosomal proteins HMG1 and HMG2 with DNA. European journal of biochemistry 34 913411
2011 The sterol-sensing domain (SSD) directly mediates signal-regulated endoplasmic reticulum-associated degradation (ERAD) of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase isozyme Hmg2. The Journal of biological chemistry 32 21628456
2009 High-mobility group protein HMGB2 regulates human erythroid differentiation through trans-activation of GFI1B transcription. Blood 32 19965638
2015 Silencing of high-mobility group box 2 (HMGB2) modulates cisplatin and 5-fluorouracil sensitivity in head and neck squamous cell carcinoma. Proteomics 31 25327479
2021 microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axis. BMC cardiovascular disorders 30 33658008
1995 Differential expression of nuclear HMG1, HMG2 proteins and H1(zero) histone in various blood cells. Cell biochemistry and function 30 7758147
1981 Comparative studies on microinjected high-mobility-group chromosomal proteins, HMG1 and HMG2. The Journal of cell biology 30 6458621
2017 HMGB2 expression is associated with transition from a quiescent to an activated state of adult neural stem cells. Developmental dynamics : an official publication of the American Association of Anatomists 29 28771884
2016 HMGB2 regulates satellite-cell-mediated skeletal muscle regeneration through IGF2BP2. Journal of cell science 29 27672022
2013 Characterizations of two grass carp Ctenopharyngodon idella HMGB2 genes and potential roles in innate immunity. Developmental and comparative immunology 29 23756189
2013 Aberrant neural stem cell proliferation and increased adult neurogenesis in mice lacking chromatin protein HMGB2. PloS one 29 24391977
2005 Recombinant derivatives of the human high-mobility group protein HMGB2 mediate efficient nonviral gene delivery. The FEBS journal 29 16098203
2022 HMGB2 causes photoreceptor death via down-regulating Nrf2/HO-1 and up-regulating NF-κB/NLRP3 signaling pathways in light-induced retinal degeneration model. Free radical biology & medicine 28 35091064
2000 High affinity binding of proteins HMG1 and HMG2 to semicatenated DNA loops. BMC molecular biology 28 11041984
1997 Nuclear accumulation of HMG2 protein is mediated by basic regions interspaced with a long DNA-binding sequence, and retention within the nucleus requires the acidic carboxyl terminus. Biochemistry 28 9166769
1998 Abundance of mRNAs encoding HMG1/HMG2 class high-mobility-group DNA-binding proteins are differentially regulated in cotyledons of Pharbitis nil. Plant molecular biology 27 9617797
2021 HMGB2 orchestrates mitotic clonal expansion by binding to the promoter of C/EBPβ to facilitate adipogenesis. Cell death & disease 26 34215724
2019 MicroRNA-329 upregulation impairs the HMGB2/β-catenin pathway and regulates cell biological behaviors in melanoma. Journal of cellular physiology 26 31219186
2018 Involvement of JNK1/2-NF-κBp65 in the regulation of HMGB2 in myocardial ischemia/reperfusion-induced apoptosis in human AC16 cardiomyocytes. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 26 30119172
2008 High mobility group protein HMGB2 is a critical regulator of plasmodium oocyst development. The Journal of biological chemistry 26 18400754
1995 Repression of cell cycle progression by antisense HMG2 RNA. Biochemical and biophysical research communications 26 7763232
1984 Isolation of high-mobility-group proteins HMG1 and HMG2 in non denaturing conditions and comparison of their properties with those of acid-extracted proteins. Biochimica et biophysica acta 26 6235858
2021 The LncRNA RP11-301G19.1/miR-582-5p/HMGB2 axis modulates the proliferation and apoptosis of multiple myeloma cancer cells via the PI3K/AKT signalling pathway. Cancer gene therapy 25 33707625
2009 HMGB2 stabilizes p53 by interfering with E6/E6AP-mediated p53 degradation in human papillomavirus-positive HeLa cells. Cancer letters 25 20036050
2019 Involvement of microRNA-23b-5p in the promotion of cardiac hypertrophy and dysfunction via the HMGB2 signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 24 31103821
2019 Latexin regulation by HMGB2 is required for hematopoietic stem cell maintenance. Haematologica 23 31171637
2013 Insulin-induced gene protein (INSIG)-dependent sterol regulation of Hmg2 endoplasmic reticulum-associated degradation (ERAD) in yeast. The Journal of biological chemistry 23 23306196
2003 Molecular characterization of three 3-hydroxy-3-methylglutaryl-CoA reductase genes including pathogen-induced Hmg2 from pepper (Capsicum annuum). Biochimica et biophysica acta 23 12591612
1989 Nonhistone proteins HMG1 and HMG2 suppress the nucleosome assembly at physiological ionic strength. Biochimica et biophysica acta 23 2465778
2023 HMGB2 Deficiency Mitigates Abdominal Aortic Aneurysm by Suppressing Ang-II-Caused Ferroptosis and Inflammation via NF-κβ Pathway. Mediators of inflammation 22 38148870
2023 Structural Characteristics of High-Mobility Group Proteins HMGB1 and HMGB2 and Their Interaction with DNA. International journal of molecular sciences 21 36834988
2019 6-Gingerol Attenuates Ischemia-Reperfusion-Induced Cell Apoptosis in Human AC16 Cardiomyocytes through HMGB2-JNK1/2-NF-κB Pathway. Evidence-based complementary and alternative medicine : eCAM 21 30886640
1999 Hmg-coA reductase gene family in cotton (Gossypium hirsutum L.): unique structural features and differential expression of hmg2 potentially associated with synthesis of specific isoprenoids in developing embryos. Plant & cell physiology 21 10501034
1985 Differential binding of chromosomal proteins HMG1 and HMG2 to superhelical DNA. Biochemical and biophysical research communications 21 4084291
2021 LncRNA SNHG16 accelerates atherosclerosis and promotes ox-LDL-induced VSMC growth via the miRNA-22-3p/HMGB2 axis. European journal of pharmacology 20 34699756
2020 Long Noncoding RNA PART1 Promotes Hepatocellular Carcinoma Progression via Targeting miR-590-3p/HMGB2 Axis. OncoTargets and therapy 20 32982307
2017 Downregulation of miR-130a promotes cell growth and epithelial to mesenchymal transition by activating HMGB2 in glioma. The international journal of biochemistry & cell biology 20 28851665
2012 Anti-high mobility group box 1 and box 2 non-histone chromosomal proteins (HMGB1/HMGB2) antibodies and anti-Saccharomyces cerevisiae antibodies (ASCA): accuracy in differentially diagnosing UC and CD and correlation with inflammatory bowel disease phenotype. Journal of gastroenterology 20 22644337
1983 Comparisons of the structures of the chromosomal high mobility group proteins HMG1 and HMG2 prepared under conditions of neutral and acidic pH. Biochimica et biophysica acta 20 6221763
2018 Correlations between age, functional status, and the senescence-associated proteins HMGB2 and p16INK4a. GeroScience 19 29651745
1996 Intracellular distribution of HMG1, HMG2 and UBF change following treatment with cisplatin. Biochimica et biophysica acta 19 8679707
1987 Interaction of non-histone proteins HMG1 and HMG2 with core histones in nucleosomes and core particles revealed by chemical cross-linking. European journal of biochemistry 19 3816775
2022 Spatiotemporal expression of HMGB2 regulates cell proliferation and hepatocyte size during liver regeneration. Scientific reports 18 35831365
2019 HMGB2 is a negative regulator of telomerase activity in human embryonic stem and progenitor cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 31661640
2018 HMGB2 is a novel adipogenic factor that regulates ectopic fat infiltration in skeletal muscles. Scientific reports 18 29942000
2018 Loss of Endogenous HMGB2 Promotes Cardiac Dysfunction and Pressure Overload-Induced Heart Failure in Mice. Circulation journal : official journal of the Japanese Circulation Society 18 30487376
1996 Differential binding of HMG1, HMG2, and a single HMG box to cisplatin-damaged DNA. Toxicology and applied pharmacology 18 8975778
2023 HMGB2 is a potential diagnostic marker and therapeutic target for liver fibrosis and cirrhosis. Hepatology communications 17 37930124
2017 PDGFRA, HSD17B4 and HMGB2 are potential therapeutic targets in polycystic ovarian syndrome and breast cancer. Oncotarget 16 29050221