Affinage

HDAC2

Histone deacetylase 2 · UniProt Q92769

Length
488 aa
Mass
55.4 kDa
Annotated
2026-06-10
100 papers in source corpus 42 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HDAC2 is a class I histone deacetylase that controls gene expression programs by erasing acetyl (and acyl) marks from chromatin and from non-histone substrates, operating largely within multiprotein corepressor assemblies (PMID:37488358, PMID:19372552). As a chromatin enzyme it deacetylates histones at specific loci—removing H3K56ac at DNA double-strand breaks to promote nonhomologous end-joining and DNA repair (PMID:20802485), eliminating H3K27ac at the NLRP3 promoter to restrain BRD4–p65 recruitment and pyroptosis (PMID:38804602), and erasing H3K9 lactylation as a delactylase that limits VEGF-driven angiogenesis (PMID:38918851). Its repressive function is delivered through context-specific complexes: the NuRD complex (MTA1/2, MBD3, RBBP4/7), whose stability depends on HDAC2 itself (PMID:37488358), and assemblies with Tet2/IκBζ at the Il6 promoter (PMID:26287468), MYCN at miR-183 (PMID:23625969), XBP1s/EZH2 at the ΔNp63 promoter where it drives an H3K27ac-to-H3K27me3 switch (PMID:38413797), SMAD3/SKI (PMID:37598220), MIER3/Snail at E-cadherin (PMID:34242623), and SP1 (PMID:37205635). Beyond histones, HDAC2 deacetylates transcription factors—Gata4 (stabilized by Hopx) to restrain cardiac myocyte proliferation (PMID:20833366), CIITA to trigger its degradation (PMID:19041327), FOXO3a to repress p21 (PMID:25609639), HNF-4α (PMID:28202389), FOXA3 (PMID:35764883)—and exerts non-deacetylase activities including promotion of eIF4E sumoylation to stimulate cap-dependent translation (PMID:20421305) and delactylation of METTL3 (PMID:39950833). HDAC2 abundance and activity are tightly post-translationally controlled by CK2 phosphorylation that governs HDAC1/HDAC2 dimerization across the cell cycle (PMID:23612983), by deubiquitination (USP4, USP5, USP17) (PMID:26411366, PMID:31727867, PMID:26617781), by NEDDylation/SENP8 (PMID:25655932), and by SENP1-mediated de-SUMOylation (PMID:38822351). Through these activities HDAC2 functions in DNA damage signaling and the replication-stress checkpoint via PR130/PP2A control of ATM/CHK kinases (PMID:29472538), peripheral myelination with Sox10 (PMID:21423190), chronic pain through repression of Cacna2d1 and Kv1.2 in sensory neurons (PMID:36257688, PMID:31022463), tumor-associated macrophage polarization (PMID:37205635), and metastasis (PMID:38413797, PMID:35764883). The HDAC1 and HDAC2 paralogs are synthetically lethal in cells with hemizygous deletion of the other (PMID:37488358).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2010 High

    Established HDAC2 as a chromatin enzyme recruited directly to DNA lesions, defining a substrate-specific role (H3K56ac) in repair pathway choice rather than generic transcriptional repression.

    Evidence siRNA depletion, immunofluorescence localization to break sites, and H3K56ac assays with damage-sensitivity readouts

    PMID:20802485

    Open questions at the time
    • Does not distinguish HDAC2-specific from HDAC1-specific contribution
    • Recruitment mechanism to break sites not defined
  2. 2010 High

    Showed HDAC2 acts on non-histone substrates, deacetylating the transcription factor Gata4 (with Hopx as a stabilizing cofactor) to constrain a developmental proliferation program.

    Evidence Reciprocal Co-IP, Hopx/Hdac2 knockout mice, luciferase reporters, and cardiac myocyte proliferation quantification

    PMID:20833366

    Open questions at the time
    • Acetylation site on Gata4 not mapped
    • Whether deacetylation is direct or complex-mediated not fully resolved
  3. 2010 Medium

    Revealed a deacetylase-independent activity—HDAC2 promotes eIF4E sumoylation to drive cap-dependent translation—expanding its function beyond chromatin.

    Evidence In vitro sumoylation assays, Co-IP, and translational reporter assays

    PMID:20421305

    Open questions at the time
    • Single lab
    • Mechanism by which HDAC2 enhances SUMO conjugation unclear
  4. 2013 High

    Defined cell-cycle post-translational control: CK2 phosphorylation governs HDAC1/HDAC2 dimer assembly and dissociation, redistributing the enzymes among Sin3, NuRD, and CoREST complexes.

    Evidence Phosphosite mutagenesis, kinase inhibitors, and Co-IP across cell cycle stages

    PMID:23612983

    Open questions at the time
    • Functional consequence of mitotic dissociation on target genes not defined
  5. 2011 High

    Demonstrated a paralog-specific developmental role in which HDAC2 cooperates with Sox10 to activate the myelination transcriptional program.

    Evidence Schwann-cell-specific conditional knockout, immunofluorescence, and gene expression analysis

    PMID:21423190

    Open questions at the time
    • Direct targets of HDAC2 in the myelination program not enumerated
  6. 2015 High

    Placed HDAC2 in inflammation resolution by showing Tet2 recruits it via IκBζ to deacetylate and repress the Il6 promoter independently of DNA methylation.

    Evidence Co-IP, ChIP, knockout mice, and LPS challenge

    PMID:26287468

    Open questions at the time
    • Histone marks erased at Il6 not specified
    • Generality across inflammatory loci untested
  7. 2015 High

    Identified deubiquitination as a major control of HDAC2 abundance, with USP4 stabilizing HDAC2 to dampen p53 and NF-κB responses.

    Evidence Co-IP, ubiquitination assays, and p53 acetylation/apoptosis readouts

    PMID:26411366

    Open questions at the time
    • Ubiquitin ligase opposing USP4 not identified
  8. 2015 High

    Showed promoter-selective repression of FOXO3a targets, with HDAC2 restraining p21 transcription and oxidative stress relieving repression via Ser394 phosphorylation.

    Evidence Co-IP, ChIP, Ser394 mutagenesis, and histone acetylation assays in neurons

    PMID:25609639

    Open questions at the time
    • Kinase phosphorylating Ser394 under stress not identified
    • Basis of promoter selectivity unexplained
  9. 2015 High

    Connected HDAC2 to epigenetic reprogramming by demonstrating it supports DNMT3A2 nuclear localization required to establish genomic imprints.

    Evidence Co-IP, oocyte conditional knockout, and microinjection rescue with DNA methylation assays

    PMID:26586441

    Open questions at the time
    • Whether the effect requires deacetylase activity not tested
  10. 2018 High

    Positioned HDAC1/HDAC2 in the replication-stress checkpoint by showing they repress PR130/PP2A to maintain ATM/CHK1/CHK2 phosphorylation and prevent mitotic catastrophe.

    Evidence Genetic elimination of HDAC1/2, PR130 epistasis, and PP2A activity/phosphorylation assays

    PMID:29472538

    Open questions at the time
    • HDAC2-specific versus HDAC1-specific contribution not separated
  11. 2023 High

    Established HDAC2 as a structural determinant of NuRD integrity and chromatin accessibility, and revealed synthetic lethality with HDAC1 in paralog-deleted cells.

    Evidence dTAG-mediated degradation, ATAC-seq, NuRD proteomics, and in vivo tumor assays

    PMID:37488358

    Open questions at the time
    • Mechanism by which HDAC2 loss destabilizes other NuRD subunits not defined
  12. 2024 Medium

    Extended HDAC2 catalysis to acyl marks, identifying it as an eraser of histone H3K9 lactylation and a delactylase of METTL3, linking metabolism to chromatin and RNA modification.

    Evidence CUT&Tag, m6A sequencing, Co-IP, and overexpression/inhibitor studies

    PMID:38918851 PMID:39950833

    Open questions at the time
    • Direct catalytic delactylation versus complex-mediated effect not biochemically reconstituted
    • Single lab per substrate
  13. 2024 Medium

    Defined SUMO-based control of HDAC2 by SENP1, whose de-SUMOylation of HDAC2 promotes EGFR/AKT-driven leukemia proliferation.

    Evidence Co-IP, SUMO assays, and ChIP-qPCR at the EGFR locus with knockdown

    PMID:38822351

    Open questions at the time
    • SUMO acceptor site on HDAC2 not mapped
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HDAC2 substrate and locus selectivity is encoded—which complex compositions, post-translational states, and acyl-mark specificities direct it to particular promoters and non-histone targets—remains unresolved.
  • No structural model linking complex composition to target selection
  • Relative contributions of deacetylase, delactylase, and non-catalytic functions not unified
  • HDAC2-specific versus HDAC1-shared activities incompletely separated genome-wide

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0140110 transcription regulator activity 6 GO:0016787 hydrolase activity 3 GO:0042393 histone binding 3
Localization
GO:0005634 nucleus 5 GO:0005730 nucleolus 1 GO:0005829 cytosol 1
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3 R-HSA-73894 DNA Repair 2
Partners
EZH2HDAC1MBD3MTA1MTA2RBBP4SMAD3SP1
Complex memberships
CoRESTNuRDSin3

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 Tet2 recruits Hdac2 to the Il6 promoter via the IκBζ transcription factor, mediating histone deacetylation to repress IL-6 transcription during inflammation resolution, independent of DNA methylation or hydroxymethylation. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), genetic knockout mouse models, lipopolysaccharide challenge assays Nature High 26287468
2010 HDAC1 and HDAC2 are recruited to DNA double-strand break sites and regulate acetylation of histone H3 Lys56 (H3K56ac), promoting DNA repair by nonhomologous end-joining (NHEJ); depletion of both causes hypersensitivity to DNA-damaging agents and sustained DNA-damage signaling. siRNA knockdown, immunofluorescence localization to damage sites, H3K56 acetylation assays, cell survival assays with DNA-damaging agents Nature structural & molecular biology High 20802485
2010 Hdac2 physically interacts with the transcription factor Gata4 and mediates its deacetylation; this interaction is stabilized by Hopx. Hopx/Hdac2-mediated deacetylation of Gata4 impairs Gata4's ability to transactivate cell cycle genes, thereby restraining cardiac myocyte proliferation during embryonic development. Co-immunoprecipitation, mouse genetic knockout (Hopx and Hdac2), luciferase reporter assays, cardiac myocyte proliferation quantification Developmental cell High 20833366
2008 HDAC2 physically interacts with CIITA (MHC class II transactivator) in smooth muscle cells and macrophages, deacetylates CIITA, promotes its proteasomal degradation, decreases its recruitment to target promoters, and suppresses its transcriptional activity (MHC II activation and collagen repression). Enzyme-deficient HDAC2 does not promote CIITA degradation. Co-immunoprecipitation, HDAC inhibitor (TSA) treatment, siRNA knockdown, chromatin immunoprecipitation (ChIP), luciferase reporter assays, quantitative PCR Journal of molecular and cellular cardiology High 19041327
2015 USP4 (ubiquitin-specific peptidase 4) directly interacts with and deubiquitinates HDAC2, leading to HDAC2 stabilization. Accumulated HDAC2 in USP4-overexpressing cells compromises p53 acetylation, p53 transcriptional activation, and apoptotic response to DNA damage, and also downregulates TNFα-induced NF-κB activation. Co-immunoprecipitation, ubiquitination assays, overexpression and knockdown experiments, p53 acetylation assays, apoptosis assays Oncogene High 26411366
2010 HDAC2 promotes sumoylation of eIF4E (eukaryotic translation initiation factor 4E) independent of its deacetylase activity, inducing formation of the active eIF4F complex and stimulating cap-dependent mRNA translation of a subset of eIF4E-responsive genes essential for cell proliferation and survival. In vitro sumoylation assays, co-immunoprecipitation, overexpression studies, translational reporter assays The Journal of biological chemistry Medium 20421305
2013 Protein kinase CK2-catalyzed phosphorylation of HDAC2 (and HDAC1) during mitosis promotes dissociation of HDAC1/HDAC2 heterodimers, leaving each enzyme as homodimers associated with Sin3, NuRD, and CoREST corepressor complex components. HDAC1/HDAC2 dimerization depends on phosphorylation in interphase, and phosphorylation by CK2 is required for their dissociation during metaphase. Kinase inhibitor studies, site-directed mutagenesis of phosphorylation sites, co-immunoprecipitation across cell cycle stages, immunofluorescence The Journal of biological chemistry High 23612983
2011 In Schwann cells, HDAC2 specifically activates the transcriptional program of myelination in synergy with Sox10. Ablation of Hdac2 in Schwann cells leads to massive Schwann cell loss and virtual absence of peripheral myelin, with greatly reduced Sox10 and Krox20 expression. Conditional genetic knockout (Schwann cell-specific Hdac1 and Hdac2 deletion), immunofluorescence, gene expression analysis Nature neuroscience High 21423190
2015 HDAC2 forms a physical complex with FOXO3a and selectively enriches at the p21 gene promoter (but not other FOXO3a targets), inhibiting FOXO3a-mediated p21 transcription. Oxidative stress reduces HDAC2–FOXO3a interaction (regulated by phosphorylation at HDAC2 Ser394), leading to increased H4K16 acetylation at the p21 promoter and upregulation of p21 expression in a p53-independent manner. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), site-directed mutagenesis (Ser394), histone acetylation assays, qRT-PCR, neuronal apoptosis assays The Journal of neuroscience High 25609639
2015 HDAC2 forms a complex with DNMT3A2 in mouse embryonic stem cells; loss of HDAC1 and HDAC2 in oocytes reduces nuclear-associated DNMT3A2 and causes global DNA hypomethylation and failure to establish genomic imprints. Injection of Hdac2 into double-mutant oocytes partially restores DNMT3A2 nuclear localization. Co-immunoprecipitation (DNMT3A2–HDAC2), oocyte-specific conditional knockout, microinjection rescue experiments, DNA methylation assays Cell reports High 26586441
2018 HDAC1 and HDAC2 suppress expression of PPP2R3A/PR130 (a regulatory subunit of the serine/threonine phosphatase PP2A). PR130 promotes dephosphorylation of ATM by PP2A. Loss of HDAC1/2 upregulates PR130, leading to dephosphorylation of checkpoint kinases ATM, CHK1, CHK2, and the kinases WEE1/CDK1, impairing S-phase checkpoint and promoting mitotic catastrophe upon replicative stress. Genetic elimination of HDAC1/HDAC2, PR130 knockout epistasis, phosphorylation assays, PP2A activity assays, cell fate/apoptosis assays Nature communications High 29472538
2019 LncRNA EPB41L4A-AS1 interacts with HDAC2 and NPM1 and sequesters HDAC2 in the nucleolus. Silencing EPB41L4A-AS1 reduces HDAC2–NPM1 interaction, releases HDAC2 from the nucleolus to the nucleoplasm, enhances HDAC2 occupancy on VHL and VDAC1 promoters, and accelerates glycolysis and glutaminolysis. RNA immunoprecipitation (RIP), RNA pulldown, RNA-FISH/immunofluorescence co-localization, ChIP, siRNA knockdown EBioMedicine Medium 30796006
2016 HDAC2 promotes loss of primary cilia in pancreatic ductal adenocarcinoma cells by controlling Aurora A expression; inhibition or silencing of HDAC2 restores primary cilia formation and decreases Aurora A levels, acting independently of KRAS. siRNA silencing, pharmacological inhibition, immunofluorescence (cilia formation), Aurora A expression assays, KRAS epistasis experiments EMBO reports Medium 28028031
2015 Lamin A/C forms a protein complex with HDAC2 and histone substrates in skin fibroblasts. This interaction is dynamically reduced at the onset of DNA damage and restored after DNA repair completion, paralleling modulation of p21 (CDKN1A) expression and global histone acetylation. LMNA mutations (progeria) disrupt this interplay, causing impaired lamin A/C–HDAC2 interaction and p21 accumulation during stress recovery. Co-immunoprecipitation, western blot, oxidative stress induction, comparison between normal and HGPS patient fibroblasts, gene expression analysis Aging cell Medium 30109767
2015 USP17 interacts with HDAC2, deubiquitinates it, and stabilizes its protein level. In cigarette smoke extract-exposed airway epithelial cells and macrophages, HDAC2 is excessively ubiquitinated and degraded in the proteasome due to low USP17 expression; USP17 overexpression blocks HDAC2 destruction. Co-immunoprecipitation, ubiquitination assays, USP17 overexpression, cigarette smoke extract exposure, proteasome inhibition International journal of clinical and experimental pathology Medium 26617781
2015 NEDDylation (NEDD8 conjugation) targets HDAC2 for proteasomal degradation; HDAC2 is a substrate for NEDD8 conjugation potentiated by oxidized LDL. De-NEDDylating enzyme SENP8 and NEDD8 reciprocally regulate HDAC2 levels. HDAC2 reciprocally regulates Arginase2 transcription to modulate endothelial function. NEDD8 conjugation assays, ectopic expression of NEDD8/SENP8, pharmacological inhibition (MLN4924), Co-IP, mouse aortic ring functional assays Journal of molecular and cellular cardiology Medium 25655932
2016 HDAC2 deacetylates HNF-4α (hepatocyte nuclear factor 4α), disrupting its binding to the miR-101b promoter. Suppression of miR-101b upregulates its target AMPK, causing AD-like tau hyperphosphorylation, aggregation, and dendritic impairments. Overexpression/knockdown of HDAC2, HNF-4α deacetylation assays, chromatin immunoprecipitation, miRNA mimic/siRNA rescue experiments in AD mouse model Molecular therapy Medium 28202389
2013 MYCN recruits HDAC2 to the miR-183 promoter in neuroblastoma cells; HDAC2 depletion enhances H4 pan-acetylation at the miR-183 promoter and induces miR-183 transcription. MYCN and HDAC2 thus co-repress miR-183, a tumor suppressive microRNA. Co-immunoprecipitation (MYCN–HDAC2 complexes), chromatin immunoprecipitation (ChIP) at miR-183 promoter, HDAC2 knockdown/overexpression, H4 acetylation assays Nucleic acids research High 23625969
2016 HDAC1 and HDAC2 directly bind to the TP53 gene locus together with MYC; inhibition of HDAC1/HDAC2 with HDAC inhibitors reduces MYC recruitment to the TP53 gene and decreases mutant p53 mRNA and protein expression in pancreatic cancer cells. Chromatin immunoprecipitation (ChIP) of HDAC1, HDAC2, and MYC at TP53 locus, HDAC inhibitor treatment, genetic elimination of HDAC1/HDAC2, qRT-PCR, western blot Oncogene Medium 27721407
2023 HDAC2 controls chromatin accessibility at HDAC2–NuRD complex-bound genomic sites; targeted degradation of HDAC2 in HDAC1-deficient neuroblastoma cells prompts degradation of several NuRD complex subunits (MTA1, MTA2, MBD3, RBBP4/7) and impairs control of enhancer-associated transcription. HDAC1 and HDAC2 are synthetically lethal in cells with hemizygous deletion of the other paralog. dTAG-mediated targeted protein degradation, CRISPR genetic disruption, chromatin accessibility (ATAC-seq), proteomics, in vitro and in vivo tumor growth assays Nature structural & molecular biology High 37488358
2020 PACS-1 accumulates in the nucleus during cell cycle progression and interacts with HDAC2 (and HDAC3) to regulate chromatin dynamics by maintaining histone acetylation status. PACS-1 knockdown causes proteasome-mediated degradation of HDAC2 and HDAC3, elevated H3K9ac and H4K16ac, and increased replication stress-induced DNA damage. Co-immunoprecipitation, siRNA knockdown, histone acetylation assays, γH2AX assays, cell cycle fractionation Oncogene Medium 31988453
2022 HDAC2 constitutively enriches at the Cacna2d1 (α2δ-1) gene promoter in dorsal root ganglion (DRG) neurons to repress its transcription. Nerve injury reduces HDAC2 enrichment at this promoter, causing histone hyperacetylation, α2δ-1 upregulation, and increased NMDA receptor synaptic trafficking/activity in the spinal cord, promoting chronic pain. Conditional knockout or knockdown of Hdac2 in DRG neurons phenocopies nerve injury and is reversed by gabapentin or α2δ-1 knockout. Conditional knockout (DRG-specific Hdac2 deletion), ChIP (HDAC2 at Cacna2d1 promoter), siRNA knockdown, electrophysiology, behavioral pain assays, epistasis with Cacna2d1 knockout mice The Journal of neuroscience High 36257688
2019 HDAC2, but not HDAC1, co-localizes with Kv1.2 in NF200-positive large neurons of the DRG; HDAC2 siRNA (not HDAC1 siRNA) treatment relieves mechanical/thermal hypersensitivity and upregulates Kv1.2 expression in a CCI neuropathic pain model, establishing HDAC2 as a selective regulator of Kv1.2 gene expression in primary sensory neurons. siRNA knockdown (HDAC1 vs HDAC2), immunofluorescence co-localization, intrathecal injection, western blot, qRT-PCR, behavioral pain assays Neuroscience Medium 31022463
2016 During RANKL-induced osteoclastogenesis, HDAC2 activates Akt; Akt directly phosphorylates and inactivates FoxO1 (a negative regulator of osteoclastogenesis that reduces reactive oxygen species). HDAC2 deletion decreases Akt activation and increases FoxO1 activity, suppressing osteoclastogenesis. Lentiviral overexpression/deletion in bone marrow macrophages, western blot (Akt phosphorylation, FoxO1 activity), osteoclast differentiation assays, bone resorption assays American journal of physiology. Cell physiology Medium 26962001
2019 HDAC2 promotes FOXA3 deacetylation by interacting with FOXA3, stabilized by lncRNA DACT3-AS1. Deacetylated FOXA3 is downregulated, relieving its transcriptional repression of PKM2, thereby upregulating PKM2 to promote HCC metastasis. Co-immunoprecipitation, ChIP, RIP, western blot, overexpression/knockdown, in vivo metastasis assays Experimental & molecular medicine Medium 35764883
2019 UBIQUITIN-SPECIFIC PROTEASE 5 (USP5) interacts with and deubiquitinates HDAC2, protecting it from ubiquitin-mediated proteasomal degradation. USP5 knockdown reduces HDAC2 levels and increases p27 (cell cycle inhibitor) expression, suppressing ovarian cancer cell proliferation. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, xenograft tumor models, western blot Aging Medium 31727867
2024 HDAC2 mediates delactylation of METTL3 (m6A methyltransferase), facilitating METTL3 interaction with WTAP and increasing m6A modification of DNA damage repair transcripts, thereby promoting cisplatin resistance in triple-negative breast cancer. Co-immunoprecipitation, m6A sequencing, HDAC2 inhibitor (Tucidinostat) treatment, western blot, in vitro and in vivo cisplatin resistance assays Advanced science Medium 39950833
2024 HDAC2 suppresses chromatin accessibility at the NLRP3 promoter by eliminating H3K27 acetylation. HDAC2 knockout promotes H3K27ac-mediated recruitment of a BRD4–phospho-p65 complex to enhance NLRP3 transcription, enabling NLRP3/GSDMD-mediated pyroptosis in colorectal cancer cells. ATAC-seq, RNA-seq, ChIP-qPCR (H3K27ac, BRD4, p65), CRISPR knockout, western blot, xenograft models Clinical and translational medicine High 38804602
2024 HDAC2 acts as an eraser of H3K9 lactylation (H3K9la); hyperlactylation of H3K9 inhibits HDAC2 expression, creating a feedback loop that drives VEGF-induced angiogenesis. HDAC2 overexpression decreases H3K9 lactylation and suppresses angiogenesis in endothelial cells. CUT&Tag (H3K9la chromatin mapping), pharmacological glycolysis inhibition, HDAC2 overexpression, in vivo angiogenesis assays Genome biology Medium 38918851
2023 HDAC2 regulates the M2-like tumor-associated macrophage phenotype via histone H3 acetylation and through the transcription factor SP1. Myeloid-specific deletion of Hdac2 or pharmacological class I HDAC inhibition shifts macrophages from M2-like to M1-like, alters T-cell infiltration, and reduces tumor growth and angiogenesis in murine lung cancer models. Conditional myeloid Hdac2 knockout (four murine cancer models), pharmacological inhibition, histone acetylation assays, SP1 ChIP/co-IP, coculture systems, tumor growth assays Cancer research High 37205635
2017 TRPV1-mediated glucocorticoid receptor (GR) signaling induces HDAC2 expression in the hippocampus. In Trpv1-deficient mice, GR-mediated HDAC2 expression and activity are reduced, altering HDAC2-regulated cell-cycle- and neuroplasticity-related gene expression. Hippocampal HDAC2 knockdown phenocopies TRPV1 deficiency, and HDAC2 overexpression blocks the stress-resilient behavioral effects of TRPV1 deficiency. Trpv1 knockout mice, hippocampal siRNA knockdown, HDAC2 overexpression (viral), chronic unpredictable stress behavioral assays, western blot Cell reports Medium 28402861
2009 HDAC2 selectively deacetylates histones at chromatin, and its siRNA depletion (but not HDAC1 or HDAC6 depletion) leads to reduced expression of heterochromatin maintenance proteins, chromatin decondensation, and sensitization of breast cancer cells to topoisomerase inhibitor-induced apoptosis. HDAC2 expression correlates with HDAC inhibitor-induced histone acetylation in surrogate tissue. siRNA knockdown (HDAC1, HDAC2, HDAC6), morphological chromatin analysis, heterochromatin protein assays, apoptosis assays with topoisomerase inhibitors Molecular cancer therapeutics Medium 19372552
2024 HDAC2 enhances ACSL4 acetylation indirectly by inhibiting transcription of the deacetylase SIRT3. Separately, HAT1 directly promotes ACSL4 acetylation at lysine 383. ACSL4 acetylation inhibits FBXO10-mediated K48-linked ubiquitination, stabilizing ACSL4 and promoting ferroptosis-sensitive properties in nasopharyngeal carcinoma. Co-IP, acetylation assays (ACSL4-K383), ubiquitination assays, HDAC2 overexpression/knockdown, SIRT3 expression assays, in vitro and in vivo radiosensitivity assays Cell death & disease Medium 40050614
2023 HDAC2 forms a co-repressor complex with SMAD3 and SKI (TGF-β pathway proteins) in brain tumor stem cells (BTSCs), maintaining chromatin accessibility required for BTSC self-renewal and growth. Disruption of the HDAC2–SMAD3–SKI axis via pharmacological inhibition or genetic loss-of-function reduces tumorigenic potential in vitro and in orthotopic xenograft models. Pharmacological HDAC inhibition, genetic loss and gain of function, chromatin accessibility assays, co-immunoprecipitation, BTSC self-renewal assays, orthotopic xenograft models Nature communications Medium 37598220
2011 HDAC2 maintains HIF-1α protein stability in oral squamous cell carcinoma cells via direct physical interaction; HDAC2 overexpression prevents VHL-mediated ubiquitination of HIF-1α, while HDAC2 knockdown reduces HIF-1α levels and impairs cell invasion/migration. Co-immunoprecipitation confirmed direct interaction of HIF-1α with VHL as modulated by HDAC2. Co-immunoprecipitation (HDAC2–HIF-1α, HIF-1α–VHL), protein synthesis/degradation inhibitor studies, shRNA knockdown, overexpression, in vivo tumor models Journal of oral pathology & medicine Medium 21332579
2024 HDAC2 directly binds to the LAPTM4B promoter at four distinct sites to activate its transcription, promoting autophagy in hepatocellular carcinoma. HDAC2 binding at LAPTM4B was confirmed by ChIP, establishing LAPTM4B as a direct HDAC2 transcriptional target. ChIP (HDAC2 at LAPTM4B promoter), promoter binding site mapping, knockdown/overexpression, autophagy assays, in vivo xenograft models Cell death & disease Medium 39147759
2021 MIER3 interacts with HDAC1, HDAC2, and Snail to form a co-repressor complex that binds the E-cadherin promoter and mediates its deacetylation, promoting epithelial-mesenchymal transition in breast cancer cells. Co-immunoprecipitation (MIER3–HDAC1/HDAC2–Snail), chromatin immunoprecipitation (ChIP at E-cadherin promoter), western blot, in vitro migration/invasion assays Experimental cell research Medium 34242623
2024 SENP1 binds to HDAC2 and mediates its de-SUMOylation; SENP1-mediated de-SUMOylation of HDAC2 enhances EGFR transcription and activates the AKT signaling pathway to promote AML cell proliferation. Co-immunoprecipitation (SENP1–HDAC2), SUMO assays, ChIP-qPCR (HDAC2 at EGFR locus), shRNA/sgRNA knockdown Molecular cancer Medium 38822351
2022 HDAC2 reduces histone H3K9 acetylation at the miR-205 promoter through an SP1-mediated pathway, suppressing miR-205 expression. miR-205 in turn directly targets and inhibits HDAC2 expression, forming a feedback regulatory loop that controls ECM production in tubular epithelial cells in diabetic kidney disease. ChIP (H3K9ac at miR-205 promoter), luciferase reporter assays (miR-205 promoter), siRNA knockdown, overexpression, db/db mouse model Clinical science Medium 35084460
2019 Cytoplasmic binding between glucocorticoid receptor (GR) and HDAC2 was demonstrated in mesenchymal stem cells. VPA-mediated HDAC2 inhibition alters this GR–HDAC2 cytoplasmic interaction and leads to GR recruitment to the nGRE element of the osteocalcin (OC) promoter, downregulating OC expression. Co-immunoprecipitation (cytoplasmic GR–HDAC2), chromatin immunoprecipitation (ChIP of GR at OC nGRE), HDAC2 knockdown, in vivo bone formation assay (NOD/SCID mice) Cells Medium 30841579
2016 p21 and CK2 interaction (but not CK2 alone) enhances HDAC2 phosphorylation, which restricts KLF4 deacetylation by HDAC2 and prevents KLF4 from acting as an oncogene in bladder cancer cells. When p21 is absent, HDAC2 deacetylates KLF4, converting it from a tumor suppressor to a proliferation promoter. Co-immunoprecipitation (p21–CK2–HDAC2), phosphorylation assays, KLF4 acetylation assays, siRNA knockdown, luciferase reporter assays Tumour biology Medium 26729194
2024 Hypoxia-activated XBP1s forms a stable repressor complex with HDAC2 and EZH2. This complex binds the ΔNp63 promoter, mediating a switch from H3K27ac (normoxic state) to H3K27me3 (hypoxic state) to suppress ΔNp63α transcription and promote breast cancer metastasis. Knockdown of either HDAC2 or EZH2 restores H3K27ac and ΔNp63α expression. Co-immunoprecipitation (XBP1s–HDAC2–EZH2), ChIP (H3K27ac and H3K27me3 at ΔNp63 promoter), siRNA knockdown, pharmacological inhibition, in vivo metastasis models Cell death and differentiation High 38413797

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. Nature 680 26287468
2010 Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining. Nature structural & molecular biology 533 20802485
2009 Role of HDAC2 in the pathophysiology of COPD. Annual review of physiology 243 18817512
2010 Hdac1 and Hdac2 act redundantly to control p63 and p53 functions in epidermal progenitor cells. Developmental cell 217 21093383
2010 Overlapping functions of Hdac1 and Hdac2 in cell cycle regulation and haematopoiesis. The EMBO journal 195 20571512
2020 Inhibition of histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome editing. Nucleic acids research 193 31799598
2009 Histone deacetylase HDAC1/HDAC2-controlled embryonic development and cell differentiation. The International journal of developmental biology 148 19412887
2011 HDAC1 and HDAC2 control the transcriptional program of myelination and the survival of Schwann cells. Nature neuroscience 139 21423190
2009 HDAC2: a critical factor in health and disease. Trends in pharmacological sciences 138 19892411
2010 Regulating the regulators: the post-translational code of class I HDAC1 and HDAC2. Journal of biomedicine & biotechnology 133 21197454
2010 Hopx and Hdac2 interact to modulate Gata4 acetylation and embryonic cardiac myocyte proliferation. Developmental cell 125 20833366
2019 LncRNA EPB41L4A-AS1 regulates glycolysis and glutaminolysis by mediating nucleolar translocation of HDAC2. EBioMedicine 119 30796006
2019 The p300/YY1/miR-500a-5p/HDAC2 signalling axis regulates cell proliferation in human colorectal cancer. Nature communications 115 30737378
2008 Global histone H4 acetylation and HDAC2 expression in colon adenoma and carcinoma. Digestive diseases and sciences 105 19057998
2017 Targeting the HDAC2/HNF-4A/miR-101b/AMPK Pathway Rescues Tauopathy and Dendritic Abnormalities in Alzheimer's Disease. Molecular therapy : the journal of the American Society of Gene Therapy 102 28202389
2024 A feedback loop driven by H3K9 lactylation and HDAC2 in endothelial cells regulates VEGF-induced angiogenesis. Genome biology 98 38918851
2013 Selective HDAC1/HDAC2 inhibitors induce neuroblastoma differentiation. Chemistry & biology 98 23706636
2011 Distinct and redundant functions of histone deacetylases HDAC1 and HDAC2 in proliferation and tumorigenesis. Cell cycle (Georgetown, Tex.) 96 21270520
2015 HDAC2 selectively regulates FOXO3a-mediated gene transcription during oxidative stress-induced neuronal cell death. The Journal of neuroscience : the official journal of the Society for Neuroscience 94 25609639
2016 HDAC1 and HDAC2 integrate the expression of p53 mutants in pancreatic cancer. Oncogene 86 27721407
2013 MYCN and HDAC2 cooperate to repress miR-183 signaling in neuroblastoma. Nucleic acids research 79 23625969
2016 HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation. Cell death and differentiation 70 27082454
2008 HDAC2 deacetylates class II transactivator and suppresses its activity in macrophages and smooth muscle cells. Journal of molecular and cellular cardiology 70 19041327
2016 HDAC2 promotes loss of primary cilia in pancreatic ductal adenocarcinoma. EMBO reports 66 28028031
2015 USP4 inhibits p53 and NF-κB through deubiquitinating and stabilizing HDAC2. Oncogene 66 26411366
2013 HDAC1 and HDAC2 restrain the intestinal inflammatory response by regulating intestinal epithelial cell differentiation. PloS one 66 24040068
2018 HDAC1 and HDAC2 integrate checkpoint kinase phosphorylation and cell fate through the phosphatase-2A subunit PR130. Nature communications 65 29472538
2012 HDAC1 and HDAC2 are differentially expressed in endometriosis. Reproductive sciences (Thousand Oaks, Calif.) 65 22344732
2013 Divergent roles of HDAC1 and HDAC2 in the regulation of epidermal development and tumorigenesis. The EMBO journal 62 24240174
2022 YTHDC1 is downregulated by the YY1/HDAC2 complex and controls the sensitivity of ccRCC to sunitinib by targeting the ANXA1-MAPK pathway. Journal of experimental & clinical cancer research : CR 61 35974388
2017 HDAC2 overexpression correlates with aggressive clinicopathological features and DNA-damage response pathway of breast cancer. American journal of cancer research 59 28560068
2018 The histone deacetylases HDAC1 and HDAC2 are required for the growth and survival of renal carcinoma cells. Archives of toxicology 56 29845424
2011 HDAC2 promotes cell migration/invasion abilities through HIF-1α stabilization in human oral squamous cell carcinoma. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 56 21332579
2018 HDAC2 dysregulation in the nucleus basalis of Meynert during the progression of Alzheimer's disease. Neuropathology and applied neurobiology 54 30252960
2025 HDAC2-Mediated METTL3 Delactylation Promotes DNA Damage Repair and Chemotherapy Resistance in Triple-Negative Breast Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 53 39950833
2019 Plantamajoside attenuates isoproterenol-induced cardiac hypertrophy associated with the HDAC2 and AKT/ GSK-3β signaling pathway. Chemico-biological interactions 52 31009642
2009 HDAC2 regulates chromatin plasticity and enhances DNA vulnerability. Molecular cancer therapeutics 52 19372552
2024 Inhibition of HDAC2 sensitises antitumour therapy by promoting NLRP3/GSDMD-mediated pyroptosis in colorectal cancer. Clinical and translational medicine 51 38804602
2023 The HDAC2-SP1 Axis Orchestrates Protumor Macrophage Polarization. Cancer research 50 37205635
2017 TRPV1 Regulates Stress Responses through HDAC2. Cell reports 50 28402861
2013 Protein kinase CK2 regulates the dimerization of histone deacetylase 1 (HDAC1) and HDAC2 during mitosis. The Journal of biological chemistry 49 23612983
2019 HDAC1 and HDAC2 Double Knockout Triggers Cell Apoptosis in Advanced Thyroid Cancer. International journal of molecular sciences 47 30669676
2023 HDAC2 as a target for developing anti-cancer drugs. Computational and structural biotechnology journal 46 36968022
2019 HDAC1 and HDAC2 Regulate Intermediate Progenitor Positioning to Safeguard Neocortical Development. Neuron 45 30709655
2024 N6-methyladenosine-modified SENP1, identified by IGF2BP3, is a novel molecular marker in acute myeloid leukemia and aggravates progression by activating AKT signal via de-SUMOylating HDAC2. Molecular cancer 43 38822351
2022 HDAC2 Facilitates Pancreatic Cancer Metastasis. Cancer research 41 34903606
2018 Altered modulation of lamin A/C-HDAC2 interaction and p21 expression during oxidative stress response in HGPS. Aging cell 41 30109767
2019 HDAC2, but not HDAC1, regulates Kv1.2 expression to mediate neuropathic pain in CCI rats. Neuroscience 40 31022463
2022 miR-3189-targeted GLUT3 repression by HDAC2 knockdown inhibits glioblastoma tumorigenesis through regulating glucose metabolism and proliferation. Journal of experimental & clinical cancer research : CR 38 35260183
2021 A first-in-class anticancer dual HDAC2/FAK inhibitors bearing hydroxamates/benzamides capped by pyridinyl-1,2,4-triazoles. European journal of medicinal chemistry 37 34111829
2015 HDAC1 and HDAC2 collectively regulate intestinal stem cell homeostasis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 37 25648995
2022 HDAC2 in Primary Sensory Neurons Constitutively Restrains Chronic Pain by Repressing α2δ-1 Expression and Associated NMDA Receptor Activity. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 36257688
2019 Cytoplasmic Interactions between the Glucocorticoid Receptor and HDAC2 Regulate Osteocalcin Expression in VPA-Treated MSCs. Cells 36 30841579
2018 HDAC1 and HDAC2 Modulate TGF-β Signaling during Endothelial-to-Hematopoietic Transition. Stem cell reports 36 29641990
2020 MiR-646 prevents proliferation and progression of human breast cancer cell lines by suppressing HDAC2 expression. Molecular and cellular probes 34 32777446
2016 HDAC2 regulates FoxO1 during RANKL-induced osteoclastogenesis. American journal of physiology. Cell physiology 34 26962001
2019 ARHGAP4 regulates the cell migration and invasion of pancreatic cancer by the HDAC2/β-catenin signaling pathway. Carcinogenesis 33 30958531
2015 A DNMT3A2-HDAC2 Complex Is Essential for Genomic Imprinting and Genome Integrity in Mouse Oocytes. Cell reports 33 26586441
2023 Human bone marrow mesenchymal stem cell-derived extracellular vesicles reduce inflammation and pyroptosis in acute kidney injury via miR-223-3p/HDAC2/SNRK. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 32 36640195
2010 Expression of class I histone deacetylases (HDAC1 and HDAC2) in oesophageal adenocarcinomas: an immunohistochemical study. Journal of clinical pathology 32 20924032
2022 Hypoxia-induced LncRNA DACT3-AS1 upregulates PKM2 to promote metastasis in hepatocellular carcinoma through the HDAC2/FOXA3 pathway. Experimental & molecular medicine 30 35764883
2016 The role of HDAC2 in chromatin remodelling and response to chemotherapy in ovarian cancer. Oncotarget 30 26683361
2010 HDAC2 promotes eIF4E sumoylation and activates mRNA translation gene specifically. The Journal of biological chemistry 30 20421305
2023 Collateral lethality between HDAC1 and HDAC2 exploits cancer-specific NuRD complex vulnerabilities. Nature structural & molecular biology 29 37488358
2021 GPR126 regulates colorectal cancer cell proliferation by mediating HDAC2 and GLI2 expression. Cancer science 28 33629464
2020 HDAC2 promotes the EMT of colorectal cancer cells and via the modular scaffold function of ENSG00000274093.1. Journal of cellular and molecular medicine 28 33325150
2018 HDAC2 attenuates airway inflammation by suppressing IL-17A production in HDM-challenged mice. American journal of physiology. Lung cellular and molecular physiology 27 30407865
2015 NEDDylation promotes endothelial dysfunction: a role for HDAC2. Journal of molecular and cellular cardiology 27 25655932
2015 Inactivation of HDAC1 or HDAC2 induces gamma globin expression without altering cell cycle or proliferation. American journal of hematology 27 25808664
2017 Reduced HDAC2 in skeletal muscle of COPD patients. Respiratory research 26 28526090
2024 Electro-acupuncture inhibits HDAC2 via modulating gut microbiota to ameliorate SNI-induced pain and depression-like behavior in rats. Journal of affective disorders 25 38395201
2019 HDAC1 and HDAC2 independently regulate common and specific intrinsic responses in murine enteroids. Scientific reports 25 30926862
2016 p21 and CK2 interaction-mediated HDAC2 phosphorylation modulates KLF4 acetylation to regulate bladder cancer cell proliferation. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 25 26729194
2024 HDAC2 promotes autophagy-associated HCC malignant progression by transcriptionally activating LAPTM4B. Cell death & disease 24 39147759
2022 The HDAC2/SP1/miR-205 feedback loop contributes to tubular epithelial cell extracellular matrix production in diabetic kidney disease. Clinical science (London, England : 1979) 24 35084460
2019 HDAC2-mediated upregulation of IL-6 triggers the migration of osteosarcoma cells. Cell biology and toxicology 24 30706385
2019 Ubiquitin specific peptidase 5 promotes ovarian cancer cell proliferation through deubiquitinating HDAC2. Aging 24 31727867
2024 Hypoxia-activated XBP1s recruits HDAC2-EZH2 to engage epigenetic suppression of ΔNp63α expression and promote breast cancer metastasis independent of HIF1α. Cell death and differentiation 23 38413797
2023 Epigenetic and molecular coordination between HDAC2 and SMAD3-SKI regulates essential brain tumour stem cell characteristics. Nature communications 23 37598220
2020 The multifunctional protein PACS-1 is required for HDAC2- and HDAC3-dependent chromatin maturation and genomic stability. Oncogene 23 31988453
2020 Elevated miR-23a impairs trophoblast migration and invasiveness through HDAC2 inhibition and NF-κB activation. Life sciences 23 32866518
2021 Histone deacetylase HDAC2 silencing prevents endometriosis by activating the HNF4A/ARID1A axis. Journal of cellular and molecular medicine 22 34586697
2019 Expression of Histone Deacetylases HDAC1 and HDAC2 and Their Role in Apoptosis in the Penumbra Induced by Photothrombotic Stroke. Molecular neurobiology 22 31493239
2017 H3K9ac and HDAC2 Activity Are Involved in the Expression of Monocarboxylate Transporter 1 in Oligodendrocyte. Frontiers in molecular neuroscience 22 29184483
2014 VPA inhibits renal cancer cell migration by targeting HDAC2 and down-regulating HIF-1α. Molecular biology reports 22 24390319
2022 Sp1 Inhibits PGC-1α via HDAC2-Catalyzed Histone Deacetylation in Chronic Constriction Injury-Induced Neuropathic Pain. ACS chemical neuroscience 21 36401579
2023 HDAC2 exacerbates rheumatoid arthritis progression via the IL-17-CCL7 signaling pathway. Environmental toxicology 20 37021908
2021 JAK-STAT Pathway Inhibition Partially Restores Intestinal Homeostasis in Hdac1- and Hdac2-Intestinal Epithelial Cell-Deficient Mice. Cells 20 33498747
2021 HDAC2 and 7 down-regulation induces senescence in dermal fibroblasts. Aging 20 34253688
2015 USP17-mediated deubiquitination and stabilization of HDAC2 in cigarette smoke extract-induced inflammation. International journal of clinical and experimental pathology 20 26617781
2021 Chronic restraint stress impairs cognition via modulating HDAC2 expression. Translational neuroscience 19 33986954
2020 HDAC2-mediated proliferation of trophoblast cells requires the miR-183/FOXA1/IL-8 signaling pathway. Journal of cellular physiology 19 33164209
2017 Immunoexpression of HDAC1, HDAC2, and HAT1 in actinic cheilitis and lip squamous cell carcinoma. Oral diseases 19 28107582
2025 HAT1/HDAC2 mediated ACSL4 acetylation confers radiosensitivity by inducing ferroptosis in nasopharyngeal carcinoma. Cell death & disease 18 40050614
2021 MIER3 induces epithelial-mesenchymal transition and promotes breast cancer cell aggressiveness via forming a co-repressor complex with HDAC1/HDAC2/Snail. Experimental cell research 18 34242623
2019 HDAC2 Regulates Glial Cell Activation in Ischemic Mouse Retina. International journal of molecular sciences 18 31627491
2018 Capsaicin upregulates HDAC2 via TRPV1 and impairs neuronal maturation in mice. Experimental & molecular medicine 18 29520110
2016 HDAC2 promotes the migration and invasion of non-small cell lung cancer cells via upregulation of fibronectin. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 18 27665474
2011 HDAC2 and TXNL1 distinguish aneuploid from diploid colorectal cancers. Cellular and molecular life sciences : CMLS 18 21290163
2018 Clinicopathological features and prediction values of HDAC1, HDAC2, HDAC3, and HDAC11 in classical Hodgkin lymphoma. Anti-cancer drugs 17 29481474

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