Affinage

HDAC9

Histone deacetylase 9 · UniProt Q9UKV0

Length
1011 aa
Mass
111.3 kDa
Annotated
2026-06-10
100 papers in source corpus 22 papers cited in narrative 22 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

HDAC9 is a class IIa histone deacetylase that functions as a signal-responsive transcriptional repressor, controlling differentiation programs in muscle, immune, skeletal, and vascular lineages through both catalytic deacetylation and corepressor scaffolding (PMID:11535832, PMID:11390982). Its founding activity is repression of MEF2-dependent transcription: HDAC9 and its catalytically inactive splice isoform MITR bind directly to the MADS/MEF2 domain of MEF2 proteins and recruit corepressors including HDAC1 and CtBP through a conserved P-X-D-L-R motif, with CtBP-dependent and -independent repression operating in parallel (PMID:11535832, PMID:10487760, PMID:11022042). This repression is switched off by phosphorylation of Ser-218 and Ser-448, which promotes 14-3-3 binding, disrupts the MEF2 interaction, alters nuclear distribution, and relieves silencing of muscle-specific genes (PMID:11390982). Beyond histone substrates, HDAC9 deacetylates the transcription factor FoxO1 to drive hepatic gluconeogenic gene expression (PGC-1α, CREB, GR) (PMID:28733598), and it acts at chromatin through targeted histone deacetylation—repressing TIMP3 and the Foxp3 locus, and controlling H3K9 acetylation at autophagy gene promoters (ATG7, BECN1, LC3a/b) to govern lineage differentiation (PMID:30715128, PMID:34006836, PMID:32620134). In vascular smooth muscle cells HDAC9 assembles a ternary repressive complex with the chromatin remodeler BRG1 and the lncRNA MALAT1 to silence contractile genes and, via NF-κB activation, promotes vascular calcification, driving aneurysm and calcification pathology in vivo (PMID:29520069, PMID:31659325, PMID:35894849). HDAC9 also restrains osteoclastogenesis and adipogenesis through a mutually suppressive loop with PPARγ/RANKL signaling in concert with SMRT/NCoR corepressors (PMID:25793404, PMID:21247904). Across multiple cancers HDAC9 acts as a pro-tumorigenic regulator, repressing p53 and ERα and supporting proliferation and survival (PMID:31451695, PMID:31099456, PMID:26380023).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 High

    Established that an HDAC9 isoform represses MEF2-dependent transcription by directly engaging MEF2 and recruiting deacetylase machinery, defining HDAC9 as a MEF2 corepressor.

    Evidence Yeast two-hybrid, direct binding and transcription assays in Xenopus embryos (MITR–MEF2D/A binding, HDAC1 recruitment)

    PMID:10487760

    Open questions at the time
    • Did not establish the catalytic contribution of full-length HDAC9
    • Physiological gene targets of MEF2 repression not defined
  2. 2001 High

    Defined HDAC9 as a catalytically active deacetylase with multiple isoforms (including catalytic-domain-lacking MITR) and confirmed MEF2 repression, while delineating CtBP-dependent and -independent repression routes.

    Evidence Cloning, in vitro deacetylase assays, CtBP-motif mutagenesis, Co-IP, reporter assays

    PMID:11022042 PMID:11535832

    Open questions at the time
    • Endogenous histone substrates not mapped
    • Relative contributions of catalytic vs scaffolding repression unresolved
  3. 2001 High

    Identified the phosphorylation/14-3-3 switch that converts HDAC9/MITR from repressor to permissive state, explaining how external signals release MEF2-dependent muscle genes.

    Evidence Site-directed mutagenesis of Ser-218/Ser-448, Co-IP, immunofluorescence, myogenic differentiation assays

    PMID:11390982

    Open questions at the time
    • Kinases phosphorylating these serines not identified in this work
    • Mechanism of nuclear redistribution not structurally resolved
  4. 2009 High

    Linked HDAC9 to regulatory T cell suppressive function via HSP70 and Foxp3, extending its repressor role into immune tolerance.

    Evidence HDAC9 knockout mice, Treg transfer, HSP70–Foxp3 Co-IP, HSP70 inhibition/overexpression, colitis model

    PMID:19879272

    Open questions at the time
    • Direct deacetylation target in this axis not defined
    • Whether effect is catalytic or scaffolding unclear
  5. 2011 Medium

    Showed HDAC9/MITR directs mesenchymal lineage choice toward osteogenesis by directly antagonizing PPARγ-2 transcriptional activity.

    Evidence EZH2 ChIP-on-chip, differentiation assays, PPARγ-2 interaction studies

    PMID:21247904

    Open questions at the time
    • Interaction not validated by reciprocal Co-IP
    • Single lab
  6. 2015 High

    Established HDAC9 as a suppressor of osteoclastogenesis through a mutual PPARγ/RANKL feedback loop acting with SMRT/NCoR, demonstrated to be hematopoietic-intrinsic.

    Evidence HDAC9 KO mice, bone marrow transplantation, ex vivo osteoclast differentiation, corepressor interaction assays

    PMID:25793404

    Open questions at the time
    • Direct chromatin targets in osteoclast precursors not mapped
  7. 2015 Medium

    Extended HDAC9 corepressor activity to neuromuscular plasticity, showing collaboration with Dach2 to suppress reinnervation genes Myog and Gdf5.

    Evidence Loss-of-function in mouse skeletal muscle, gene expression and epistasis analysis

    PMID:26483211

    Open questions at the time
    • Direct vs indirect regulation of Myog/Gdf5 promoters not resolved
    • Molecular nature of Dach2–HDAC9 cooperation undefined
  8. 2015 Medium

    Implicated HDAC9 as pro-tumorigenic in multiple contexts—upstream of TAZ in glioblastoma, repressing p53 at its promoter in osteosarcoma, and driving retinoblastoma cell cycle progression.

    Evidence Knockdown/overexpression, rescue epistasis, ChIP of p53 promoter, cell cycle/xenograft assays

    PMID:25760078 PMID:26380023 PMID:27033599

    Open questions at the time
    • Direct vs indirect TAZ regulation unclear
    • Each finding single lab and tumor-type specific
  9. 2016 Medium

    Demonstrated that HDAC9 overexpression in B cells drives lymphomagenesis through BCL6 and p53 pathway modulation.

    Evidence Eμ-HDAC9 transgenic mice, gene expression profiling, BCL6/p53 pathway analysis

    PMID:27799148

    Open questions at the time
    • Direct molecular targets of HDAC9 in B cells not defined
    • Catalytic requirement not tested
  10. 2017 Medium

    Identified a non-histone substrate by showing HDAC9 deacetylates FoxO1 to amplify hepatic gluconeogenic gene programs, a pathway co-opted during HCV infection.

    Evidence FoxO1 deacetylation assay, gene expression of PGC-1α/CREB/GR, FoxO1 promoter binding analysis, HCV model

    PMID:28733598

    Open questions at the time
    • Direct deacetylation residues not mapped
    • Single lab
  11. 2018 High

    Defined a ternary HDAC9–BRG1–MALAT1 chromatin complex that silences VSMC contractile genes with H3K27me3 gain, linking HDAC9 to aneurysm pathology.

    Evidence Co-IP of ternary complex, ChIP for H3K27me3, Malat1/Hdac9 loss-of-function, in vivo aneurysm model

    PMID:29520069

    Open questions at the time
    • Stoichiometry and assembly order of the complex unresolved
    • Whether HDAC9 catalytic activity is required not isolated
  12. 2018 Medium

    Placed HDAC9 upstream of both IκBα/NF-κB and MAPK signaling in driving ischemic brain inflammatory injury.

    Evidence HDAC9 KO mice, ischemia/reperfusion model, phospho-protein western blots, LPS cell model with MAPK rescue

    PMID:30031609

    Open questions at the time
    • Direct molecular link between HDAC9 and these signaling nodes undefined
    • Single lab
  13. 2019 High

    Established HDAC9 as a driver of vascular calcification with reduced contractility, confirmed by complementary gain/loss-of-function and in vivo KO.

    Evidence Gain/loss-of-function in human aortic SMCs, HDAC9 KO in MGP-deficient mice, calcification assays

    PMID:31659325

    Open questions at the time
    • Mechanistic chromatin targets in calcifying SMCs not detailed in this study
  14. 2019 Medium

    Extended HDAC9's promoter-level repression to trophoblast invasion (TIMP3) and antiestrogen resistance (ERα) and to gastric cancer growth and chemosensitivity.

    Evidence Knockdown/overexpression, ChIP-qPCR of TIMP3 promoter acetylation, ERα activity assays, gastric xenografts with cisplatin

    PMID:30715128 PMID:31099456 PMID:31451695

    Open questions at the time
    • ERα regulation mechanism (direct vs indirect) not fully resolved
    • Each context single lab
  15. 2020 Medium

    Showed HDAC9 controls autophagy gene expression via H3K9 deacetylation at ATG7, BECN1, and LC3a/b promoters, coupling its activity to age-related skeletal stem cell lineage shifts.

    Evidence ChIP for H3K9ac at autophagic gene promoters, TEM/confocal, micro-CT, HDAC9 inhibitor treatment in aged mice

    PMID:32620134

    Open questions at the time
    • Direct binding of HDAC9 to these promoters vs indirect effect not fully separated
    • Single lab
  16. 2021 Medium

    Positioned HDAC9 downstream of IL-4/STAT6 in deacetylating the Foxp3 locus to limit chromatin accessibility and regulatory T cell differentiation.

    Evidence STAT6-dependence experiments, chromatin accessibility assays, pan-HDAC inhibitor rescue, allergic airway model

    PMID:34006836

    Open questions at the time
    • Pan-HDAC inhibitor not HDAC9-specific
    • Direct recruitment mechanism to Foxp3 locus undefined
  17. 2022 High

    Confirmed NF-κB activation as the effector pathway for HDAC9-driven VSMC calcification and identified β-hydroxybutyrate as a suppressor of HDAC9 expression.

    Evidence RNA-seq, gain/loss-of-function, NF-κB inhibition rescue, calcification assays, CKD rat/mouse models

    PMID:35894849

    Open questions at the time
    • Mechanism by which HDAC9 activates NF-κB not molecularly defined
    • Direct chromatin targets in this axis unmapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether HDAC9's many context-specific phenotypes depend on catalytic deacetylation versus corepressor scaffolding, and the direct genomic and non-histone substrate repertoire in each tissue, remain unresolved.
  • No catalytic-dead vs scaffolding-only structure-function dissection across tissues
  • Genome-wide direct HDAC9 binding map absent
  • Non-histone substrate spectrum beyond FoxO1 uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0042393 histone binding 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0016787 hydrolase activity 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 1
Partners
BRG1CTBPFOXO1HDAC1MEF2AMEF2DPPARGYWHA(14-3-3)
Complex memberships
HDAC9-MALAT1-BRG1 ternary repressive complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 HDAC9 (and its isoform HDAC9a) contains an HDAC catalytic domain and Flag-tagged HDAC9/HDAC9a possess deacetylase activity in vitro. HDAC9 has multiple alternatively spliced isoforms, including MITR which lacks the catalytic domain. HDAC9 and HDAC9a repress MEF2-mediated transcription. Cloning, in vitro deacetylase activity assay, reporter gene assay Proceedings of the National Academy of Sciences of the United States of America High 11535832
1999 MITR (an HDAC9 isoform lacking a catalytic domain) binds directly to the MADS/MEF-2 domain of MEF2 proteins (MEF2D and MEF2A) but not to SRF, and represses MEF2-dependent transcription by recruiting HDAC1. Yeast two-hybrid screen, functional transcription assay, direct binding experiments in Xenopus embryo model The EMBO journal High 10487760
2001 MITR (HDAC9 isoform) interacts with the transcriptional corepressor CtBP through a conserved P-X-D-L-R motif. Mutation of this motif abolishes CtBP interaction and impairs (but does not eliminate) MEF2 transcriptional repression. Residual repressive activity of CtBP-binding mutants is attributable to association with other HDAC family members, revealing CtBP-dependent and -independent mechanisms for transcriptional repression by MITR. Co-immunoprecipitation, mutagenesis of CtBP-binding motif, reporter gene transcription assay The Journal of biological chemistry High 11022042
2001 MITR (HDAC9 isoform) is a signal-responsive inhibitor of myogenesis. Phosphorylation of Ser-218 and Ser-448 stimulates binding of 14-3-3 to MITR, disrupts MEF2:MITR interactions, alters nuclear distribution of MITR, and relieves repression of muscle-specific gene expression. A Ser→Ala double mutant acts as a potent repressor of myogenesis, confirming these serines as the regulatory switch. Site-directed mutagenesis, co-immunoprecipitation, immunofluorescence localization, reporter gene assay, myogenic differentiation assay Proceedings of the National Academy of Sciences of the United States of America High 11390982
2009 HDAC9 deletion in T regulatory cells (Tregs) leads to increased expression of HSP70, and immunoprecipitation experiments revealed a direct interaction between HSP70 and Foxp3. Inhibition of HSP70 reduced the suppressive functions of HDAC9-/- Tregs, while Tregs overexpressing HSP70 had increased suppressive functions. HDAC9-/- mice were resistant to colitis development. HDAC9 knockout mice, Treg transfer experiments, co-immunoprecipitation (HSP70–Foxp3 interaction), HSP70 inhibition/overexpression assays Gastroenterology High 19879272
2015 HDAC9 promotes glioblastoma tumor formation via interaction with TAZ (a Hippo pathway effector). Knockdown of HDAC9 decreased TAZ expression, and overexpression of TAZ in HDAC9-knockdown cells abrogated the effects of HDAC9 silencing on proliferation and tumor formation, placing HDAC9 upstream of TAZ in the EGFR signaling pathway. HDAC9 knockdown, TAZ overexpression rescue, in vitro proliferation assay, in vivo tumor formation assay Oncotarget Medium 25760078
2015 HDAC9 inhibits osteoclast differentiation and bone resorption through a mutual suppression loop with PPARγ/RANKL signaling. HDAC9 forms a negative regulatory loop: PPARγ and NF-κB suppress HDAC9 expression, while HDAC9 inhibits PPARγ activity in synergy with SMRT/NCoR corepressors. HDAC9 knockout mice exhibit elevated bone resorption and lower bone mass, and bone marrow transplantation confirms the effect is intrinsic to hematopoietic lineage. HDAC9 knockout mice, bone marrow transplantation, ex vivo osteoclast differentiation assay, HDAC9 overexpression, co-repressor interaction assays Molecular endocrinology High 25793404
2011 MITR (HDAC9c isoform) promotes osteogenesis and inhibits adipogenesis of mesenchymal stem cells by directly interacting with PPARγ-2 in the nucleus of osteoblasts, thereby interrupting PPARγ-2 transcriptional activity and preventing adipogenesis. EZH2-ChIP-on-chip to identify MITR as target, functional differentiation assays, co-immunoprecipitation/interaction studies with PPARγ-2 The Journal of biological chemistry Medium 21247904
2015 Dach2 and Hdac9 act collaboratively as activity-regulated transcriptional co-repressors to inhibit reinnervation of denervated mouse skeletal muscle. They inhibit denervation-dependent induction of Myog and Gdf5 gene expression. Myog and Gdf5 appear to stimulate reinnervation through parallel pathways (Myog does not regulate Gdf5 transcription). Dach2 and Hdac9 loss-of-function in mouse skeletal muscle, gene expression analysis, epistasis experiments Development Medium 26483211
2017 HDAC9 regulates hepatic gluconeogenesis by deacetylating FoxO1 (post-translational modification). HDAC9 also regulates gluconeogenic transcription factors PGC-1α, CREB, and GR by altering gene expression via the FoxO1 deacetylation pathway. PGC-1α, CREB and GR are upregulated in response to HDAC9 via FoxO1 deacetylation, and HDAC9-FoxO1 signaling is induced by HCV infection to exaggerate gluconeogenesis. Deacetylation assay of FoxO1, gene expression analysis, FoxO1 binding site analysis in promoters of PGC-1α/CREB/GR, HCV infection model Scientific reports Medium 28733598
2018 HDAC9 forms a ternary complex with the chromatin-remodeling enzyme BRG1 and the lncRNA MALAT1. This HDAC9-MALAT1-BRG1 complex binds chromatin and represses contractile protein gene expression in vascular smooth muscle cells (VSMCs) in association with gain of histone H3-lysine 27 trimethylation. Disruption of Malat1 or Hdac9 restores contractile protein expression, improves aortic mural architecture, and inhibits experimental aneurysm growth. Co-immunoprecipitation of ternary complex, ChIP assay (H3K27me3), loss-of-function (Malat1 or Hdac9 disruption), in vivo aneurysm model Nature communications High 29520069
2019 Increased expression of HDAC9 in human aortic smooth muscle cells promotes calcification and reduces contractility; inhibition of HDAC9 inhibits calcification and enhances cell contractility. HDAC9-knockout mice show 40% reduction in aortic calcification and improved survival in a vascular calcification model. HDAC9 gain- and loss-of-function in human aortic smooth muscle cells, HDAC9 knockout mice in matrix Gla protein-deficient background, calcification assays Nature genetics High 31659325
2018 HDAC9 promotes brain ischemic injury by activating IκBα/NF-κB and MAPK signaling pathways. HDAC9 knockout reduces infarct volume, improves neurological function, and suppresses expression of iNOS, COX-2, IL-1β, IL-6, TNF-α, and IL-18 in ischemia/reperfusion injury. In vitro, HDAC9 inhibition-reduced inflammation through the IκBα/NF-κB pathway is reversed by promoting MAPK activity, placing HDAC9 upstream of both pathways. HDAC9 knockout mice, ischemia/reperfusion model, western blot for phosphorylated NF-κB/IκBα/MAPKs, LPS-stimulated cell model with pathway rescue Biochemical and biophysical research communications Medium 30031609
2019 HDAC9 knockdown inhibits cell growth, reduces colony formation, and induces apoptosis and cell cycle arrest in gastric cancer cells, and suppresses tumor growth in vivo. HDAC9 siRNA enhanced antitumor efficacy of cisplatin in gastric cancer. HDAC9 siRNA knockdown, in vitro proliferation/apoptosis/cell cycle assays, in vivo xenograft model Experimental & molecular medicine Medium 31451695
2016 HDAC9 deregulated expression in B cells (Eμ-HDAC9 transgenic mice) promotes development of splenic marginal zone lymphoma and lymphoproliferative disease progressing to DLBCL. HDAC9 appears to contribute to lymphomagenesis by modulating BCL6 activity and p53 tumor suppressor function. Eμ-HDAC9 transgenic mouse model, gene expression profiling, analysis of BCL6 and p53 pathways Disease models & mechanisms Medium 27799148
2019 In MCF7 breast cancer cells, HDAC9 overexpression decreased ERα mRNA and protein expression and inhibited ERα transcriptional activity. HDAC9-overexpressing cells were less sensitive to tamoxifen antiproliferative effects, demonstrating a mechanistic role for HDAC9 in antiestrogen resistance through suppression of ERα signaling. HDAC9 overexpression in MCF7 cells, transcriptomic analysis, ERα expression and activity assays, antiproliferative assay Molecular oncology Medium 31099456
2019 HDAC9 dysregulation in trophoblast cells promotes cell migration and invasion by repressing TIMP3 expression through promoter histone hypoacetylation. HDAC9 knockdown in HTR-8/SVneo cells inhibited migration and invasion, and was associated with upregulation of TIMP3 due to histone hyperacetylation at the TIMP3 promoter detected by ChIP-qPCR. HDAC9 knockdown, transwell migration/invasion assays, ChIP-qPCR of TIMP3 promoter histone acetylation American journal of hypertension Medium 30715128
2021 IL-4 inhibits regulatory T cell differentiation and Foxp3 expression through a STAT6-dependent mechanism involving HDAC9-mediated histone deacetylation at the Foxp3 locus, decreasing chromatin accessibility and Foxp3 gene transcription. HDAC9 involvement assay, STAT6-dependence experiments, chromatin accessibility assay, pan-HDAC inhibitor rescue, mouse model of allergic airway inflammation Cell death & disease Medium 34006836
2022 β-hydroxybutyrate (BHB) downregulates HDAC9 expression and suppresses vascular calcification. HDAC9 promotes VSMC calcification via activation of the NF-κB signaling pathway; inhibition of NF-κB attenuated HDAC9-induced VSMC calcification. Both pharmacological inhibition and knockdown of HDAC9 attenuated calcification, while HDAC9 overexpression exacerbated it. RNA-seq, RT-qPCR, western blot, HDAC9 knockdown/overexpression, NF-κB inhibition rescue, calcification assays in VSMCs and aortic rings, in vivo CKD rat and mouse models The Journal of pathology High 35894849
2020 HDAC9 regulates autophagy in bone marrow mesenchymal stem cells (BMMSCs) by controlling H3K9 acetylation at the promoters of autophagic genes ATG7, BECN1, and LC3a/b, thereby affecting lineage differentiation. Elevated HDAC9 in aged mice impairs autophagy and shifts BMMSCs toward adipogenesis; HDAC9 inhibition restored lineage differentiation and improved bone mass. Western blot, ChIP assay (H3K9ac at autophagic gene promoters), TEM/confocal microscopy, micro-CT, HDAC9 inhibitor treatment Stem cell research & therapy Medium 32620134
2015 HDAC9 knockdown in retinoblastoma cells induces cell cycle arrest at G1 phase with significant decrease in cyclin E2 and CDK2 expression, inhibits proliferation in vitro, and inhibits tumor growth in vivo. HDAC9 knockdown, cell cycle analysis (flow cytometry), western blot for cyclin E2/CDK2, xenograft tumor model Biochemical and biophysical research communications Medium 27033599
2015 HDAC9 epigenetically represses p53 transcription in osteosarcoma cells by binding to the p53 proximal promoter region, as demonstrated by ChIP assay. HDAC9 overexpression promoted cell proliferation and invasion. ChIP assay (HDAC9 binding to p53 promoter), HDAC9 overexpression, proliferation and invasion assays International journal of clinical and experimental medicine Medium 26380023

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 New and emerging HDAC inhibitors for cancer treatment. The Journal of clinical investigation 1126 24382387
2016 HDACs and HDAC Inhibitors in Cancer Development and Therapy. Cold Spring Harbor perspectives in medicine 1040 27599530
2009 Multiple roles of HDAC inhibition in neurodegenerative conditions. Trends in neurosciences 532 19775759
2008 Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders. Current opinion in pharmacology 359 18206423
2016 HDAC and HDAC Inhibitor: From Cancer to Cardiovascular Diseases. Chonnam medical journal 353 26865995
2010 Targeting the correct HDAC(s) to treat cognitive disorders. Trends in pharmacological sciences 300 20980063
2018 Advances and Challenges of HDAC Inhibitors in Cancer Therapeutics. Advances in cancer research 277 29551127
2021 Epigenetic modulation and understanding of HDAC inhibitors in cancer therapy. Life sciences 274 33872660
2012 HDAC inhibitor-based therapies: can we interpret the code? Molecular oncology 271 23141799
2001 Cloning and characterization of a histone deacetylase, HDAC9. Proceedings of the National Academy of Sciences of the United States of America 210 11535832
2009 Enhancing the apoptotic and therapeutic effects of HDAC inhibitors. Cancer letters 204 19359091
2009 Inhibition of HDAC9 increases T regulatory cell function and prevents colitis in mice. Gastroenterology 203 19879272
2011 Histone deacetylase (HDAC) inhibition as a novel treatment for diabetes mellitus. Molecular medicine (Cambridge, Mass.) 198 21274504
2008 HDACs and HDAC inhibitors in colon cancer. Epigenetics 187 18326939
2001 Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting transcription repressor (MITR) contributes to transcriptional repression of the MEF2 transcription factor. The Journal of biological chemistry 185 11022042
1999 MEF-2 function is modified by a novel co-repressor, MITR. The EMBO journal 171 10487760
2019 HDAC Inhibitors in Acute Myeloid Leukemia. Cancers 158 31739588
2019 Safety and Tolerability of Histone Deacetylase (HDAC) Inhibitors in Oncology. Drug safety 153 30649740
2014 HDAC inhibitors and immunotherapy; a double edged sword? Oncotarget 145 25115382
2005 Dietary HDAC inhibitors: time to rethink weak ligands in cancer chemoprevention? Carcinogenesis 139 16267097
2016 Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-κB-mediated inflammation. Current opinion in chemical biology 130 27371876
2019 HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype. Nature genetics 122 31659325
2018 An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm. Nature communications 122 29520069
2009 HDAC inhibitor-based therapies and haematological malignancy. Annals of oncology : official journal of the European Society for Medical Oncology 119 19515748
2010 HDAC inhibitors and neurodegeneration: at the edge between protection and damage. Pharmacological research 115 20123018
2015 ApoE4 and Aβ Oligomers Reduce BDNF Expression via HDAC Nuclear Translocation. The Journal of neuroscience : the official journal of the Society for Neuroscience 113 25972179
2012 HDAC inhibitors: roles of DNA damage and repair. Advances in cancer research 112 23088869
2015 HDAC Inhibitors as Novel Anti-Cancer Therapeutics. Recent patents on anti-cancer drug discovery 108 25782916
2014 HDAC signaling in neuronal development and axon regeneration. Current opinion in neurobiology 108 24727244
2022 Target deconvolution of HDAC pharmacopoeia reveals MBLAC2 as common off-target. Nature chemical biology 99 35484434
2005 Genome-wide analysis of HDAC function. Trends in genetics : TIG 99 16153738
2016 How do tumor cells respond to HDAC inhibition? The FEBS journal 94 27112360
2001 The transcriptional corepressor MITR is a signal-responsive inhibitor of myogenesis. Proceedings of the National Academy of Sciences of the United States of America 93 11390982
2012 Expression noise and acetylation profiles distinguish HDAC functions. Molecular cell 91 22683268
2013 HDAC-dependent ventricular remodeling. Trends in cardiovascular medicine 90 23499301
2011 The biology of HDAC in cancer: the nuclear and epigenetic components. Handbook of experimental pharmacology 87 21879444
2020 Comprehensive review for anticancer hybridized multitargeting HDAC inhibitors. European journal of medicinal chemistry 84 33077264
2006 The molecular mechanism of HDAC inhibitors in anticancer effects. Cellular & molecular immunology 78 16978537
2014 Vascular histone deacetylation by pharmacological HDAC inhibition. Genome research 73 24732587
2020 Recent Update of HDAC Inhibitors in Lymphoma. Frontiers in cell and developmental biology 72 33015069
2022 HDAC6: A unique HDAC family member as a cancer target. Cellular oncology (Dordrecht, Netherlands) 71 36036883
2011 HDAC inhibition and graft versus host disease. Molecular medicine (Cambridge, Mass.) 68 21298214
2015 HDAC9 promotes glioblastoma growth via TAZ-mediated EGFR pathway activation. Oncotarget 65 25760078
2019 Precision Targeting with EZH2 and HDAC Inhibitors in Epigenetically Dysregulated Lymphomas. Clinical cancer research : an official journal of the American Association for Cancer Research 62 30979734
2019 Zinc-dependent Deacetylase (HDAC) Inhibitors with Different Zinc Binding Groups. Current topics in medicinal chemistry 61 30674261
2022 HDAC Inhibitors: Innovative Strategies for Their Design and Applications. Molecules (Basel, Switzerland) 60 35163980
2012 HDAC inhibitor therapy in autoimmunity and transplantation. Annals of the rheumatic diseases 59 22460138
2010 Histone deacetylase (HDAC) 1 and 2 expression and chemotherapy in gastric cancer. Annals of surgical oncology 58 20585871
2021 Backstage players of fibrosis: NOX4, mTOR, HDAC, and S1P; companions of TGF-β. Cellular signalling 57 34438016
2015 HDAC9 Inhibits Osteoclastogenesis via Mutual Suppression of PPARγ/RANKL Signaling. Molecular endocrinology (Baltimore, Md.) 56 25793404
2011 Susceptibility variants on chromosome 7p21.1 suggest HDAC9 as a new candidate gene for male-pattern baldness. The British journal of dermatology 54 22032556
2023 Single Inhibitors versus Dual Inhibitors: Role of HDAC in Cancer. ACS omega 52 37214715
2020 HDAC inhibition reduces white matter injury after intracerebral hemorrhage. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 50 32703113
2011 HDAC inhibitors and cancer therapy. Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques 50 21141730
2011 Myocyte enhancer factor-2 interacting transcriptional repressor (MITR) is a switch that promotes osteogenesis and inhibits adipogenesis of mesenchymal stem cells by inactivating peroxisome proliferator-activated receptor gamma-2. The Journal of biological chemistry 50 21247904
2020 Anticancer properties of chimeric HDAC and kinase inhibitors. Seminars in cancer biology 49 33189849
2017 Epigenetics in osteoarthritis: Potential of HDAC inhibitors as therapeutics. Pharmacological research 49 28827187
2022 Current trends in development of HDAC-based chemotherapeutics. Life sciences 48 36096240
2021 Metabolism, HDACs, and HDAC Inhibitors: A Systems Biology Perspective. Metabolites 47 34822450
2011 Hdac-mediated control of endochondral and intramembranous ossification. Critical reviews in eukaryotic gene expression 47 22077150
2017 Interstrand Crosslink Repair as a Target for HDAC Inhibition. Trends in pharmacological sciences 46 28687272
2017 Combination Therapies Targeting HDAC and IKK in Solid Tumors. Trends in pharmacological sciences 46 29233541
2022 Downregulation of HDAC9 by the ketone metabolite β-hydroxybutyrate suppresses vascular calcification. The Journal of pathology 45 35894849
2011 HDAC inhibition in lupus models. Molecular medicine (Cambridge, Mass.) 45 21327298
2016 Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice. Disease models & mechanisms 43 27799148
2019 Targeting HDAC Complexes in Asthma and COPD. Epigenomes 42 34968229
2016 Histone deacetylases (HDAC) in physiological and pathological bone remodelling. Bone 42 27913271
2014 Pazopanib and HDAC inhibitors interact to kill sarcoma cells. Cancer biology & therapy 42 24556916
2021 Histone deacetylase (HDAC) 9: versatile biological functions and emerging roles in human cancer. Cellular oncology (Dordrecht, Netherlands) 41 34318404
2020 Bifunctional HDAC Therapeutics: One Drug to Rule Them All? Molecules (Basel, Switzerland) 41 32987782
2019 Identification of HDAC9 as a viable therapeutic target for the treatment of gastric cancer. Experimental & molecular medicine 41 31451695
2018 HDAC9 promotes brain ischemic injury by provoking IκBα/NF-κB and MAPKs signaling pathways. Biochemical and biophysical research communications 38 30031609
2012 HDAC inhibitors and chaperone function. Advances in cancer research 38 23088873
2019 Role of HDAC inhibitors in diabetes mellitus. Current research in translational medicine 37 31477543
2016 Downregulation of HDAC9 inhibits cell proliferation and tumor formation by inducing cell cycle arrest in retinoblastoma. Biochemical and biophysical research communications 35 27033599
2019 Increased expression of the HDAC9 gene is associated with antiestrogen resistance of breast cancers. Molecular oncology 34 31099456
2017 Chidamide tablets: HDAC inhibition to treat lymphoma. Drugs of today (Barcelona, Spain : 1998) 34 28447074
2021 Designing HDAC-PROTACs: lessons learned so far. Future medicinal chemistry 33 34951318
2020 Emodin and emodin-rich rhubarb inhibits histone deacetylase (HDAC) activity and cardiac myocyte hypertrophy. The Journal of nutritional biochemistry 33 32007664
2023 The application of PROTAC in HDAC. European journal of medicinal chemistry 32 37607440
2019 Dysregulation of HDAC9 Represses Trophoblast Cell Migration and Invasion Through TIMP3 Activation in Preeclampsia. American journal of hypertension 32 30715128
2015 Dach2-Hdac9 signaling regulates reinnervation of muscle endplates. Development (Cambridge, England) 32 26483211
2017 Role of HDAC9-FoxO1 Axis in the Transcriptional Program Associated with Hepatic Gluconeogenesis. Scientific reports 31 28733598
2022 Determination of Slow-Binding HDAC Inhibitor Potency and Subclass Selectivity. ACS medicinal chemistry letters 29 35586419
2020 HDAC and MAPK/ERK Inhibitors Cooperate To Reduce Viability and Stemness in Medulloblastoma. Journal of molecular neuroscience : MN 29 32056089
2020 Impaired autophagy triggered by HDAC9 in mesenchymal stem cells accelerates bone mass loss. Stem cell research & therapy 29 32620134
2018 Multimodal HDAC Inhibitors with Improved Anticancer Activity. Current cancer drug targets 29 28176653
2023 Recent advancement of HDAC inhibitors against breast cancer. Medical oncology (Northwood, London, England) 27 37294406
2023 A Bifunctional PARP-HDAC Inhibitor with Activity in Ewing Sarcoma. Clinical cancer research : an official journal of the American Association for Cancer Research 26 37279093
2017 APOL1, CDKN2A/CDKN2B, and HDAC9 polymorphisms and small vessel ischemic stroke. Acta neurologica Scandinavica 26 28975602
2016 Identification of HDAC Inhibitors Using a Cell-Based HDAC I/II Assay. Journal of biomolecular screening 26 26858181
2016 HDAC9 regulates ox-LDL-induced endothelial cell apoptosis by participating in inflammatory reactions. Frontiers in bioscience (Landmark edition) 26 27100479
2024 Overview of class I HDAC modulators: Inhibitors and degraders. European journal of medicinal chemistry 25 39094429
2021 IL-4 inhibits regulatory T cells differentiation by HDAC9-mediated epigenetic regulation. Cell death & disease 25 34006836
2015 Up-regulation of HDAC9 promotes cell proliferation through suppressing p53 transcription in osteosarcoma. International journal of clinical and experimental medicine 25 26380023
2022 Recent Progress in Histone Deacetylase (HDAC) 1 Inhibitors as Anticancer Agent. Current cancer drug targets 24 35747969
2022 Butyrate Lowers Cellular Cholesterol through HDAC Inhibition and Impaired SREBP-2 Signalling. International journal of molecular sciences 24 36555149
2020 MicroRNA‑936 inhibits the malignant phenotype of retinoblastoma by directly targeting HDAC9 and deactivating the PI3K/AKT pathway. Oncology reports 24 31922233
2014 HDAC as a therapeutic target for treatment of endometrial cancers. Current pharmaceutical design 23 23888962
2007 Exercise and MEF2-HDAC interactions. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme 23 18059609

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