Affinage

HDAC1

Histone deacetylase 1 · UniProt Q13547

Length
482 aa
Mass
55.1 kDa
Annotated
2026-06-10
100 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HDAC1, the human ortholog of yeast RPD3 (PMID:8646880), is a class I zinc-dependent lysine deacylase that erases multiple short-chain acyl marks from histones—removing acetyl, succinyl (PMID:37580347), and L-/D-lactyl (PMID:35044827) groups—and is enzymatically active only when assembled into multi-protein corepressor complexes, co-purifying with HDAC2 and HDAC3 (PMID:15043985). Beyond histones, it deacetylates non-histone substrates including CDK1, AIFM1, MSH6 and RuvB-like 1 (PMID:30421914), JAK1 (at K1109, controlling its proteasomal stability and STAT3-driven transcription) (PMID:39384195), FoxO3a (driving atrophy gene programs and muscle fiber atrophy) (PMID:24463822), β-catenin (PMID:37667133), and HMGB1 (PMID:34815344). HDAC1 is recruited to specific genomic loci by transcription factors and corepressor scaffolds—p63 (PMID:21093383), Ets-1 (PMID:22266280), FRA1:c-JUN (PMID:36067301), DNTTIP1 (PMID:35689852), SP1 (PMID:32743904), Atrophin/RERE via ELM2-SANT domains (PMID:18451879), and MIER1/MIER2 ELM2 domains (PMID:28046085)—where it represses target genes through histone deacetylation, yet it is paradoxically also required to maintain histone acetylation at super-enhancers that drive activation programs such as the pluripotency network, with H2BK5 and H2BK11 being its most sensitive substrates (PMID:39704107). Its activity is governed by post-translational modifications: CK2 phosphorylation promotes activity and controls mitotic dissociation of the HDAC1/HDAC2 heterodimer (PMID:23612983), EGFR-mediated Tyr72 phosphorylation stabilizes the protein and supports its anti-apoptotic function (PMID:33976119), self-acetylation inactivates HDAC1 and trans-represses HDAC2 (PMID:16762839, PMID:33187090), and protein levels are set by competing ubiquitin ligases (KBTBD4 via the UM171 molecular glue (PMID:39939761), TRIM46 (PMID:34459501)) and the deubiquitinase USP19 (PMID:27517492). Functionally, HDAC1 occupies pathway positions upstream of cell-cycle and DNA-damage checkpoints—suppressing the PP2A subunit PR130 to sustain ATM/CHK1/CHK2/WEE1/CDK1 phosphorylation (PMID:29472538) and partnering with FUS in double-strand-break repair (PMID:24036913)—and has isoform-specific, only partially HDAC2-compensated roles in Schwann cell survival via β-catenin (PMID:21423190), epidermal progenitor and keratinocyte programs (PMID:21093383), β-cell proliferation through the Cdkn1b/p27 locus (PMID:30322885), and glioma stem cell identity in a p53-dependent manner (PMID:34494550).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1996 High

    Establishing the molecular identity of HDAC1 was the prerequisite for all mechanistic study—cloning revealed it as the human RPD3 counterpart, framing it as a transcriptional regulator.

    Evidence cDNA cloning, sequence alignment, and FISH mapping from human fetal lung library

    PMID:8646880

    Open questions at the time
    • Cloning alone did not establish enzymatic activity or substrates
    • No complex membership defined
  2. 2004 Medium

    Resolved whether HDAC1 is an autonomous enzyme—showing it is catalytically active only within multi-protein complexes, co-purifying with HDAC2/HDAC3.

    Evidence Nickel-affinity purification of His-tagged HDAC1 from mammalian cells with deacetylase activity assays

    PMID:15043985

    Open questions at the time
    • Did not define which corepressor complex confers activity
    • Tag effect on activity not fully resolved mechanistically
  3. 2006 High

    Identified a built-in inhibitory switch—acetylation of HDAC1 itself inactivates its deacetylase activity, allowing context-dependent conversion between repression and coactivation.

    Evidence In vitro deacetylase assay of purified acetylated HDAC1, acetylation-site mutagenesis, ChIP, and reporter assays in a GR system

    PMID:16762839

    Open questions at the time
    • Acetyltransferase responsible not defined here
    • Generalizability beyond GR context unaddressed
  4. 2008 Medium

    Defined how HDAC1 is targeted to chromatin—Atrophin/RERE recruits it through ELM2-SANT domains into a G9a-containing repressive complex to establish H3K9 methylation.

    Evidence Co-IP, chromosomal co-localization, and Drosophila genetic interaction with histone modification assays

    PMID:18451879

    Open questions at the time
    • Direct vs indirect HDAC1-G9a contact not resolved
    • Vertebrate validation limited
  5. 2011 High

    Demonstrated non-redundant paralog roles in vivo—HDAC1 controls Schwann cell survival via β-catenin while HDAC2 drives myelination, refuting simple functional equivalence.

    Evidence Schwann cell-specific conditional knockout mouse genetics with β-catenin activity and histological readouts

    PMID:21423190

    Open questions at the time
    • Mechanism linking HDAC1 to β-catenin levels not fully defined
    • Degree of compensation context-specific
  6. 2013 High

    Linked HDAC1 directly to genome maintenance and mitotic regulation—FUS-HDAC1 interaction supports DSB repair, and CK2 phosphorylation drives mitotic heterodimer dissociation.

    Evidence Co-IP, DSB recruitment, ALS mutant analysis (FUS); kinase inhibition and phospho-site mutagenesis during mitosis (CK2)

    PMID:23612983 PMID:24036913

    Open questions at the time
    • Whether HDAC1 deacetylase activity per se is required at DSBs not isolated
    • Functional consequence of homodimer state during metaphase incompletely mapped
  7. 2018 Medium

    Expanded the HDAC1 substrate landscape beyond histones and positioned it within checkpoint signaling—substrate trapping identified protein targets, and HDAC1/2 were shown to suppress PR130/PP2A to sustain checkpoint kinase phosphorylation.

    Evidence Catalytically-dead mutant substrate trapping with MS (substrates); genetic elimination of HDAC1/2 and PR130 with checkpoint phosphorylation and HR assays

    PMID:29472538 PMID:30421914

    Open questions at the time
    • Individual trapped substrates not each orthogonally validated
    • Direct deacetylation sites for checkpoint factors not mapped
  8. 2022 High

    Established HDAC1 as a histone delactylase and broad short-chain de-acylase, redefining it as a multi-mark eraser rather than a pure deacetylase.

    Evidence In vitro enzymatic screen with cellular validation of de-L-lactylase activity

    PMID:35044827

    Open questions at the time
    • Genomic distribution of lactyl marks regulated by HDAC1 not mapped here
    • Physiological consequences cell-type-specific
  9. 2023 High

    Showed HDAC1 governs metabolite- and acyl-mark-linked transcription—it is a primary desuccinylase, is inhibited by the glycolytic intermediate PEP to activate Wnt/β-catenin, and shows collateral synthetic lethality with HDAC2 through NuRD-dependent enhancer transcription.

    Evidence Reconstituted desuccinylase assays and ChIP-seq; in vitro PEP inhibition with β-catenin acetylation and xenografts; dTAG degradation with ATAC-seq/ChIP-seq

    PMID:37488358 PMID:37580347 PMID:37667133

    Open questions at the time
    • How succinyl-mark removal integrates with deacetylation at single loci unclear
    • Breadth of metabolite-sensing inhibition beyond PEP unknown
  10. 2025 High

    Defined the structural basis of pharmacological HDAC1 degradation and uncovered PTM-linked metabolic control—UM171 acts as a molecular glue recruiting KBTBD4 to HDAC1/2, while K412 lactylation tunes ferroptosis resistance.

    Evidence Cryo-EM with base editor scanning and proteomics (KBTBD4); MS site mapping with ChIP and m6A assays in vivo (K412 lactylation)

    PMID:39888307 PMID:39939761

    Open questions at the time
    • Endogenous physiological trigger for K412 lactylation not defined
    • Selectivity of glue-induced degradation across complexes incompletely mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how HDAC1 mechanistically maintains, rather than removes, histone acetylation at super-enhancers, and how its choice between repressive and activating chromatin states is encoded by complex composition and its own PTMs.
  • No structural model reconciling repressor vs enhancer-maintenance functions
  • Rules selecting corepressor complex (Sin3/NuRD/CoREST) at a given locus undefined
  • Integration of competing ubiquitination inputs (KBTBD4, TRIM46, USP19) into net abundance not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0140110 transcription regulator activity 5 GO:0016787 hydrolase activity 3 GO:0042393 histone binding 3
Localization
GO:0000228 nuclear chromosome 5 GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-4839726 Chromatin organization 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 3 R-HSA-73894 DNA Repair 3
Partners
BAP1DNTTIP1FUSHDAC2HDAC3KBTBD4MIER2USP19
Complex memberships
CoRESTLSD1-CoRESTNuRDSin3

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2022 HDAC1 (and HDAC2/3) are histone delactylases: they cleave ε-N-L-lactyllysine (K(L-la)) and K(D-la) marks from histones in vitro, and de-L-lactylase activity of HDAC1 was confirmed in cells. HDAC1-3 also remove diverse short-chain acyl modifications beyond acetyl groups. In vitro enzymatic screen with zinc- and NAD-dependent HDACs; cellular validation of de-L-lactylase activity Science advances High 35044827
2023 HDAC1/2/3 (class I HDACs) are the primary histone desuccinylases: inhibition or depletion of HDAC1/2/3 markedly increases global histone succinylation, while ectopic expression of catalytically active HDAC1/2/3 reduces it. Reconstituted HDAC1/2/3 complexes show robust desuccinylase activity in vitro. Histone succinylation is enriched at gene promoters and positively correlates with transcriptional activity. In vitro desuccinylase assay with reconstituted complexes; gain- and loss-of-function cell experiments; active-site mutant controls; genomic landscape analysis (ChIP-seq) Cell discovery High 37580347
2013 FUS directly interacts with HDAC1 (co-immunoprecipitation). This FUS–HDAC1 interaction is required for proper DNA double-strand break (DSB) damage response signaling and repair in neurons. ALS-associated FUS mutants show diminished interaction with HDAC1 and are defective in DNA damage response. Co-immunoprecipitation; recruitment of FUS to DSB sites; analysis of familial ALS FUS mutants; DNA damage assays in neurons and ALS patient tissue Nature neuroscience High 24036913
2006 HDAC1 serves as a coactivator for the glucocorticoid receptor (GR). A subfraction of HDAC1 becomes acetylated after GR association; acetylation of HDAC1 inactivates its deacetylase activity in vitro, and mutation of the critical acetylation sites abrogates HDAC1 function in vivo. HDAC1 on transcriptionally active chromatin shows low acetylation, while repressed chromatin-associated HDAC1 is highly acetylated. In vitro deacetylase activity assay of purified acetylated HDAC1; site-directed mutagenesis of acetylation sites; chromatin immunoprecipitation; in vivo reporter assays Molecular cell High 16762839
2013 Protein kinase CK2 phosphorylates HDAC1 and HDAC2 during mitosis, which is required for dissociation of the HDAC1/HDAC2 heterodimer. During metaphase, HDAC1 and HDAC2 dissociate from each other but each remains associated with corepressor complex components (Sin3, NuRD, CoREST) as homodimers. Enzymatic inhibition studies and mutational analyses confirmed that CK2-catalyzed phosphorylation is crucial for this dissociation. Kinase inhibition studies; site-directed mutagenesis of phosphorylation sites; co-immunoprecipitation during mitosis; cell fractionation The Journal of biological chemistry High 23612983
2025 UM171 acts as a molecular glue that induces high-affinity interaction between KBTBD4 (a CRL3 E3 ligase substrate receptor) and HDAC1/2, targeting HDAC1/2 for degradation within the LSD1-CoREST corepressor complex. Cryo-EM revealed an asymmetric assembly where a single UM171 molecule enables one KBTBD4 KELCH-repeat propeller to engage the HDAC1 catalytic domain (partially masking its active-site rim) while a second propeller strengthens binding cooperatively. Endogenous inositol hexakisphosphate acts as a second molecular glue stabilizing the interaction. Base editor scanning of KBTBD4 and HDAC1 confirmed the functional relevance of these interfaces. Cryo-EM structure determination; proteomics; chemical inhibitor studies; base editor scanning mutagenesis; co-immunoprecipitation Nature High 39939761
2018 HDAC1/2 suppress expression of PPP2R3A/PR130, a regulatory subunit of the trimeric serine/threonine phosphatase PP2A. This suppression sustains phosphorylation of checkpoint kinases ATM, CHK1, CHK2, as well as WEE1 and CDK1, during replicative stress. PR130 promotes dephosphorylation of ATM by PP2A; genetic elimination of PR130 altered S-phase checkpoint and DNA damage response. Genetic elimination of HDAC1/2 and PR130; kinase activity assays; checkpoint phosphorylation analysis; homologous recombination assays Nature communications High 29472538
2021 EGFR phosphorylates HDAC1 at tyrosine 72 (Tyr72), which is necessary for HDAC1 protein stability. This EGFR-mediated tyrosine phosphorylation mediates HDAC1's anti-apoptotic function. Prior work had established serine phosphorylation by CK2 promotes HDAC1 deacetylase activity; the EGFR pathway represents an alternative, distinct regulatory mechanism. Site-directed mutagenesis of Tyr72; EGFR activity modulation; apoptosis assays; protein stability measurements Cell death & disease Medium 33976119
2017 USP19, a deubiquitinase, physically interacts with HDAC1/2 and specifically regulates their K63-linked ubiquitination. USP19 translocates to the nucleus upon ionizing radiation and its activity is required for proper DNA damage response. Loss of USP19 leads to genomic instability through impaired HDAC1/2-dependent DNA damage repair. Co-immunoprecipitation; K63-linked ubiquitination assay; nuclear translocation by imaging; DNA damage assays after IR Oncotarget Medium 27517492
2018 HDAC1 substrate profiling using a mutant-trapping strategy combined with mass spectrometry identified CDK1, AIFM1, MSH6, and RuvB-like 1 as HDAC1 substrates, revealing roles of HDAC1 beyond histone deacetylation. Proteomics-based substrate trapping using catalytically inactive HDAC1 mutant combined with mass spectrometry ACS chemical biology Medium 30421914
2016 Acetylation of HDAC1 (via acetyltransferases) attenuates HDAC1 activity and trans-represses HDAC2 activity through HDAC1/HDAC2 dimerization, converting the corepressor complex into an activator complex during erythropoiesis. During erythropoiesis, global HDAC activity is dramatically reduced, linked to HDAC1 acetylation. Biochemical analysis of HDAC1 acetylation; dimerization studies; HDAC activity assays during erythroid differentiation International journal of molecular sciences Medium 33187090
2008 Atrophin (Drosophila)/RERE (vertebrate) recruits HDAC1/2 through its ELM2-SANT domains to form a complex with histone methyltransferase G9a. This complex co-occupies chromosomal loci in Drosophila to establish H3K9 methylation and gene repression, controlling wing vein and melanotic-mass cell fate decisions. Co-immunoprecipitation; chromosomal co-localization; Drosophila genetic interaction studies; histone modification assays EMBO reports Medium 18451879
2012 Ets-1 transcription factor physically interacts with HDAC1 and co-expression of Ets-1 with HDAC1 synergistically represses IL-10 transcription in Th1 cells. Loss of Ets-1 reduces HDAC1 enrichment at Il10 regulatory regions with concomitant increased histone H3 acetylation. Co-immunoprecipitation; chromatin immunoprecipitation; luciferase reporter assay; Ets-1 knockout cells Journal of immunology Medium 22266280
2021 BAP1 forms a trimeric protein complex with HMGB1 and HDAC1 that modulates HMGB1 acetylation and its secretion. Reduced BAP1 levels cause increased ubiquitylation and degradation of HDAC1, leading to increased acetylation of HMGB1 and its active secretion, which promotes mesothelial cell transformation. Co-immunoprecipitation; ubiquitylation assays; HMGB1 acetylation measurement; cell transformation assays; patient serum analysis Proceedings of the National Academy of Sciences of the United States of America Medium 34815344
2023 ENO2-derived phosphoenolpyruvate (PEP) selectively inhibits HDAC1 activity, increasing acetylation of β-catenin and activating the Wnt/β-catenin pathway in colorectal cancer cells. This identifies PEP as an endogenous metabolite inhibitor of HDAC1. In vitro HDAC1 enzymatic activity assay with PEP; β-catenin acetylation measurement; pathway activation assays; xenograft models Nature metabolism Medium 37667133
2025 TRIM46 is a ubiquitin E3 ligase that targets HDAC1 for ubiquitination and proteasomal degradation. The TRIM46–HDAC1 axis regulates genes involved in DNA replication and repair, and TRIM46 overexpression promotes breast cancer cell proliferation and chemoresistance. Co-immunoprecipitation; ubiquitination assay; CRISPR/Cas9 homologous recombination to recreate SNP; in vitro and in vivo proliferation/chemoresistance assays The EMBO journal Medium 34459501
2014 HDAC1 is sufficient to activate FoxO transcription factors and induce muscle fiber atrophy in vivo, requiring its deacetylase activity. This involves deacetylation of FoxO3a and induction of atrophy genes including atrogin-1. Dominant-negative HDAC1 (deacetylase-dead) blocked these effects, establishing deacetylase activity as mechanistically required. In vivo expression of wild-type and dominant-negative HDAC1 plasmids; FoxO acetylation and activity assays; gene expression analysis; muscle fiber size measurements Journal of cell science Medium 24463822
2023 HDAC1 and HDAC2 are synthetically lethal with each other when one paralog is hemizygously deleted (collateral synthetic lethality). Mechanistically, targeted degradation of HDAC2 in HDAC1-deficient neuroblastoma cells promotes degradation of NuRD complex subunits, diminishes chromatin accessibility at HDAC2-NuRD-bound sites, and impairs enhancer-associated transcription. dTAG-mediated protein degradation; genetic disruption; ATAC-seq; ChIP-seq; in vitro and in vivo tumor growth assays Nature structural & molecular biology High 37488358
2025 Rapid HDAC1 degradation (via dTAG within 1 hour) in mouse ESCs lacking HDAC2 revealed that H2BK5 and H2BK11 are the most sensitive substrates for HDAC1. Upregulated genes showed increased H2BK5ac and H3K27ac at their TSS. Paradoxically, the most strongly downregulated genes showed decreased acetylation and chromatin accessibility at super-enhancers, demonstrating that HDAC1 is required to maintain histone acetylation at critical enhancer regions for the pluripotency gene network. dTAG rapid degradation system (<1 hour); histone acetylation mass spectrometry; RNA-seq time course; ATAC-seq; H3K27ac ChIP-seq Nucleic acids research High 39704107
2004 Recombinant HDAC1 expressed in mammalian cells is only active as a multi-protein complex; the purified His-tagged HDAC1 preparation co-purifies with endogenous HDAC2 and HDAC3, demonstrating that HDAC1 requires complex formation for enzymatic activity. Removal of the His-tag increased activity 2–4 fold. Stable expression of His-tagged HDAC1 in mammalian cells; nickel affinity purification; Western blot identification of co-purifying HDACs; deacetylase activity assay Life sciences Medium 15043985
2017 The ELM2 domain of MIER1 and MIER2 (but not MIER3) is required for HDAC1 recruitment. MIER2, but not MIER3, co-immunoprecipitates with HDAC1 in a cell-line-dependent manner, and MIER2 complexes have associated deacetylase activity. A conserved tryptophan residue (W228) in the ELM2 domain is critical for HDAC1 recruitment. Co-immunoprecipitation; deacetylase activity assay; deletion analysis; site-directed mutagenesis of ELM2 domain PloS one Medium 28046085
2022 HDAC1 deacetylates JAK1 at lysine 1109; HDAC1 inhibition by SAHA increases JAK1 acetylation at K1109, promoting its proteasomal degradation and reducing STAT3-driven FGL1 transcription. This was established by co-immunoprecipitation showing HDAC1 as an essential deacetylase of JAK1, and by mass spectrometry identification of the specific acetylation site. Co-immunoprecipitation; mass spectrometry identifying JAK1 K1109 acetylation; proteasomal degradation assay; ChIP for STAT3 at FGL1 promoter; RNA-seq Journal for immunotherapy of cancer Medium 39384195
2025 HDAC1 K412 lactylation is essential for regulation of ferroptosis resistance in colorectal cancer. HDAC inhibitors (SAHA and TSA) specifically diminish HDAC1 K412 lactylation, leading to increased H3K27 acetylation of FTO and ALKBH5, activation of these m6A erasers, reduced m6A modification of FSP1 mRNA, and its degradation, sensitizing cells to ferroptosis. Drug screening; mass spectrometry identification of HDAC1 K412 lactylation; ChIP for H3K27ac at FTO/ALKBH5; m6A quantification; in vivo xenograft models Advanced science Medium 39888307
2016 HDAC1 and HDAC2 directly bind to the TP53 gene locus (demonstrated by ChIP) and contribute to maintaining mutant p53 expression in pancreatic cancer. MYC also directly binds the TP53 locus, and MYC recruitment drops upon HDAC inhibitor treatment, suggesting a class I HDAC-MYC cooperative mechanism at the TP53 gene. Chromatin immunoprecipitation (ChIP) for HDAC1, HDAC2, and MYC at TP53 gene; genetic siRNA knockdown; HDAC inhibitor treatment; RT-PCR and Western blot for mutant p53 Oncogene Medium 27721407
2022 Inflammation-driven NF-κB signaling recruits HDAC1 (and HDAC3) to the antioxidant response element (ARE) in the Slc40a1 (ferroportin) promoter in macrophages. HDAC1 and HDAC3 recruitment is dependent on NF-κB signaling and leads to repression of ferroportin transcription, contributing to anemia of inflammation. Chromatin immunoprecipitation (ChIP) for HDAC1/3 at Slc40a1 ARE; pharmacological and targeted RNAi screens; NF-κB signaling inhibition Blood Medium 39656097
2011 In Schwann cells, HDAC1 controls Schwann cell survival by regulating levels of active β-catenin, while HDAC2 (not HDAC1) activates the transcriptional program of myelination in synergy with Sox10. These represent distinct, non-redundant primary functions of the two paralogs in peripheral nervous system myelination. Conditional mouse genetics (Schwann cell-specific ablation of Hdac1 and Hdac2); expression analysis of Sox10, Krox20; β-catenin activity measurement; histological analysis of sciatic nerves Nature neuroscience High 21423190
2010 HDAC1 and HDAC2 directly mediate the repressive transcriptional functions of p63 in epidermal progenitor cells: HDACs bind and are active at promoters of p63-repressed targets (p21, 14-3-3σ, p16/INK4a) in normal keratinocytes. Loss of both HDAC1 and HDAC2 leads to increased acetylation of p53, which opposes p63 functions, and p53 is required for HDAC inhibitor-mediated p21 expression. Conditional ectodermal knockout of Hdac1/2; ChIP for HDAC binding at target promoters; p53 acetylation measurement; p53 genetic requirement analysis in keratinocytes Developmental cell High 21093383
2016 HDAC1 (and HDAC2) regulate global poly(A) RNA stability at the post-transcriptional level. Inhibition of HDAC1/2 induces widespread degradation of normally stable poly(A) RNA in mammalian and Drosophila cells. The mechanism involves CBP/p300-mediated acetylation of CAF1a (a catalytic subunit of the CCR4-CAF1-NOT deadenylase complex), which accelerates poly(A) RNA degradation. HDAC1/2 inhibition and knockdown; RNA stability assays; acetylation of CAF1a demonstrated; adipocyte differentiation model Molecular cell Medium 27635759
2019 HDAC1 regulates β-cell proliferation by deacetylating histones at the Cdkn1b/p27 locus, thereby reducing p27 expression and allowing cell cycle progression from G1 to S phase. HDAC1 overexpression increases Cyclin A2, Cyclin B1, and E2F1 expression; overexpression of p27 blocks HDAC1-mediated β-cell proliferation. HDAC1 overexpression in primary rat islets and INS-1 cells; p27 overexpression rescue experiment; cell cycle analysis; gene expression analysis The Biochemical journal Medium 30322885
1996 The human RPD3L1 gene (HDAC1) was cloned and found to be highly homologous (52% amino acid identity) to the yeast RPD3 transcription factor. The gene encodes a 482 amino acid protein and maps to chromosome band 1p34.1. cDNA cloning from human fetal lung library; sequence alignment; FISH chromosomal mapping; Northern blot expression analysis Cytogenetics and cell genetics High 8646880
2014 HDAC1 and Klf4 competitively bind to the promoter region of Klf4, with HDAC1 repressing Klf4 expression in myeloid leukemia. HDAC1 knockdown increases Klf4 expression and inhibits cell cycle progression; Klf4 overexpression can block the pro-proliferative effects of HDAC1 overexpression, and vice versa, establishing a mechanistic interplay. ChIP for HDAC1 and Klf4 at Klf4 promoter; knockdown and overexpression of HDAC1 and Klf4; rescue experiments in leukemia cell lines and in vivo Cell death & disease Medium 25341045
2021 HDAC1 (but not HDAC2) controls the transcriptional identity and survival of glioma stem cells in a p53-dependent manner; HDAC1 loss is not compensated by HDAC2 in this context (unlike in normal neural stem cells). Knockdown of HDAC1 suppresses tumor growth in patient-derived xenograft models. shRNA knockdown of HDAC1 and HDAC2; cell-based and biochemical assays; RNA-seq; patient-derived xenograft models; p53 genetic manipulation JCI insight Medium 34494550
2023 HDAC1 inhibits beige adipocyte-mediated thermogenesis by regulating histone crotonylation (H3K18cr) and acetylation (H3K18ac) at the enhancers and promoters of Pgc1α and Ucp1 genes. Deletion of Hdac1 in beige adipocytes increases H3K18cr at these regulatory regions, promoting Pgc1α/Ucp1 transcription and thermogenesis. Conditional Hdac1 deletion in beige adipocytes; H3K18cr and H3K18ac ChIP-seq; gene expression analysis; energy expenditure measurement; MS275 HDAC inhibitor treatment Cellular signalling Medium 37640195
2022 TNFα + IFNγ stimulation promotes formation of a FRA1:c-JUN:HDAC1 complex at the AP1 response element of the filaggrin (FLG) promoter, which suppresses FLG expression in keratinocytes. Co-immunoprecipitation demonstrated HDAC1 interaction with FRA1:c-JUN; HDAC1 knockdown abrogated cytokine-induced FLG suppression. DNA affinity precipitation assay; co-immunoprecipitation; HDAC1 knockdown; luciferase reporter assay; mouse models of skin inflammation Proceedings of the National Academy of Sciences of the United States of America Medium 36067301
2019 HDAC1 regulates anti-inflammatory effects of isoflurane in human monocytes by preventing NF-κB nuclear translocation. Co-immunoprecipitation showed that LPS decreased HDAC1/HDAC2 interaction, which was restored by isoflurane pretreatment. Gene silencing of HDAC1 (and HDAC2) blocked isoflurane-induced reduction of NF-κB nuclear translocation and proinflammatory cytokine production. Co-immunoprecipitation of HDAC1/2 interaction; siRNA gene silencing; NF-κB nuclear translocation assay; cytokine measurement in THP-1 cells and primary monocytes Immunology and cell biology Medium 31950542
2022 DNTTIP1 recruits HDAC1 to the DUSP2 gene promoter, maintaining a deacetylated state of histone H3K27 and suppressing DUSP2 transcription. This leads to aberrant ERK pathway activation and elevated MMP2, promoting nasopharyngeal carcinoma metastasis. ChIP assay for HDAC1 at DUSP2 promoter; co-immunoprecipitation of DNTTIP1-HDAC1 interaction; luciferase reporter assays; in vitro and in vivo metastasis assays EBioMedicine Medium 35689852
2017 SP1 recruits HDAC1 to the miR-326 gene promoter in osteosarcoma cells, causing histone deacetylation and transcriptional inhibition of miR-326. This was established by ChIP assay and DAPA, and the loss of miR-326 activates the SMO/Hedgehog pathway to promote proliferation and metastasis. ChIP assay for SP1/HDAC1 at miR-326 promoter; DNA affinity precipitation assay (DAPA); miR-326 expression after SP1/HDAC1 modulation; in vivo metastasis model Journal of cellular and molecular medicine Medium 32743904

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2022 Class I histone deacetylases (HDAC1-3) are histone lysine delactylases. Science advances 597 35044827
2013 Interaction of FUS and HDAC1 regulates DNA damage response and repair in neurons. Nature neuroscience 355 24036913
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
1996 Defective expression of plectin/HD1 in epidermolysis bullosa simplex with muscular dystrophy. The Journal of clinical investigation 192 8636409
2006 HDAC1 acetylation is linked to progressive modulation of steroid receptor-induced gene transcription. Molecular cell 153 16762839
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
2010 Regulating the regulators: the post-translational code of class I HDAC1 and HDAC2. Journal of biomedicine & biotechnology 133 21197454
2007 Expression of HDAC1 and CBP/p300 in human colorectal carcinomas. Journal of clinical pathology 124 17720775
2020 Strong photoperiod sensitivity is controlled by cooperation and competition among Hd1, Ghd7 and DTH8 in rice heading. The New phytologist 121 33089895
2014 HDAC1 activates FoxO and is both sufficient and required for skeletal muscle atrophy. Journal of cell science 114 24463822
2017 The DTH8-Hd1 Module Mediates Day-Length-Dependent Regulation of Rice Flowering. Molecular plant 108 28549969
2020 Increased activation of HDAC1/2/6 and Sp1 underlies therapeutic resistance and tumor growth in glioblastoma. Neuro-oncology 90 32328646
2016 HDAC1 and HDAC2 integrate the expression of p53 mutants in pancreatic cancer. Oncogene 86 27721407
2025 Lactylation of HDAC1 Confers Resistance to Ferroptosis in Colorectal Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 84 39888307
2017 Alternative functions of Hd1 in repressing or promoting heading are determined by Ghd7 status under long-day conditions. Scientific reports 82 28710485
2014 Inhibition of HDAC1 and DNMT1 modulate RGS10 expression and decrease ovarian cancer chemoresistance. PloS one 79 24475290
2019 Valproic acid targets HDAC1/2 and HDAC1/PTEN/Akt signalling to inhibit cell proliferation via the induction of autophagy in gastric cancer. The FEBS journal 72 31692265
2016 HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation. Cell death and differentiation 70 27082454
2017 HDAC1 and HDAC3 underlie dynamic H3K9 acetylation during embryonic neurogenesis and in schizophrenia-like animals. Journal of cellular physiology 67 28300292
2013 HDAC1 and HDAC2 restrain the intestinal inflammatory response by regulating intestinal epithelial cell differentiation. PloS one 66 24040068
2008 Atrophin recruits HDAC1/2 and G9a to modify histone H3K9 and to determine cell fates. EMBO reports 66 18451879
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
2017 EZH2 or HDAC1 Inhibition Reverses Multiple Myeloma-Induced Epigenetic Suppression of Osteoblast Differentiation. Molecular cancer research : MCR 60 28119431
2022 HDAC1: an environmental sensor regulating endothelial function. Cardiovascular research 58 34264338
2018 The histone deacetylases HDAC1 and HDAC2 are required for the growth and survival of renal carcinoma cells. Archives of toxicology 56 29845424
2023 HDAC1/2/3 are major histone desuccinylases critical for promoter desuccinylation. Cell discovery 50 37580347
2014 HDAC1 and Klf4 interplay critically regulates human myeloid leukemia cell proliferation. Cell death & disease 50 25341045
2018 miRNA-34a decreases ovarian cancer cell proliferation and chemoresistance by targeting HDAC1. Biochemistry and cell biology = Biochimie et biologie cellulaire 49 29561664
2013 Protein kinase CK2 regulates the dimerization of histone deacetylase 1 (HDAC1) and HDAC2 during mitosis. The Journal of biological chemistry 49 23612983
2021 HDAC1 and 2 regulate endothelial VCAM-1 expression and atherogenesis by suppressing methylation of the GATA6 promoter. Theranostics 47 33859766
2019 HDAC1 and HDAC2 Double Knockout Triggers Cell Apoptosis in Advanced Thyroid Cancer. International journal of molecular sciences 47 30669676
2019 Histone deacetylase 1 (HDAC1): A key player of T cell-mediated arthritis. Journal of autoimmunity 46 31883829
2019 HDAC1 and HDAC2 Regulate Intermediate Progenitor Positioning to Safeguard Neocortical Development. Neuron 45 30709655
2017 Knockdown of HDAC1 expression suppresses invasion and induces apoptosis in glioma cells. Oncotarget 44 28624794
2017 HDAC1 triggers the proliferation and migration of breast cancer cells via upregulation of interleukin-8. Biological chemistry 44 28779562
2020 NFAT2-HDAC1 signaling contributes to the malignant phenotype of glioblastoma. Neuro-oncology 42 31400279
2022 Hd1, Ghd7, and DTH8 synergistically determine the rice heading date and yield-related agronomic traits. Journal of genetics and genomics = Yi chuan xue bao 41 35248762
2016 Acetylation-Dependent Control of Global Poly(A) RNA Degradation by CBP/p300 and HDAC1/2. Molecular cell 40 27635759
2012 Interaction of Ets-1 with HDAC1 represses IL-10 expression in Th1 cells. Journal of immunology (Baltimore, Md. : 1950) 39 22266280
2018 HDAC1 Silencing in Ovarian Cancer Enhances the Chemotherapy Response. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 37 30071534
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
2004 Expression and functional characterization of recombinant human HDAC1 and HDAC3. Life sciences 37 15043985
2025 UM171 glues asymmetric CRL3-HDAC1/2 assembly to degrade CoREST corepressors. Nature 36 39939761
2020 Regulating the Regulators: The Role of Histone Deacetylase 1 (HDAC1) in Erythropoiesis. International journal of molecular sciences 36 33187090
2018 HDAC1 and HDAC2 Modulate TGF-β Signaling during Endothelial-to-Hematopoietic Transition. Stem cell reports 36 29641990
2023 ENO2-derived phosphoenolpyruvate functions as an endogenous inhibitor of HDAC1 and confers resistance to antiangiogenic therapy. Nature metabolism 35 37667133
2022 DNTTIP1 promotes nasopharyngeal carcinoma metastasis via recruiting HDAC1 to DUSP2 promoter and activating ERK signaling pathway. EBioMedicine 33 35689852
2015 HDAC1/2-Dependent P0 Expression Maintains Paranodal and Nodal Integrity Independently of Myelin Stability through Interactions with Neurofascins. PLoS biology 33 26406915
2019 Ellagic acid inhibits proliferation and migration of cardiac fibroblasts by down-regulating expression of HDAC1. The Journal of toxicological sciences 32 31168029
2015 Both Hd1 and Ehd1 are important for artificial selection of flowering time in cultivated rice. Plant science : an international journal of experimental plant biology 32 26566836
2010 Expression of class I histone deacetylases (HDAC1 and HDAC2) in oesophageal adenocarcinomas: an immunohistochemical study. Journal of clinical pathology 32 20924032
2024 HDAC inhibitor SAHA enhances antitumor immunity via the HDAC1/JAK1/FGL1 axis in lung adenocarcinoma. Journal for immunotherapy of cancer 31 39384195
2022 Autophagy targets Hd1 for vacuolar degradation to regulate rice flowering. Molecular plant 31 35591785
2020 Molecular mechanisms underlying eicosapentaenoic acid inhibition of HDAC1 and DNMT expression and activity in carcinoma cells. Biochimica et biophysica acta. Gene regulatory mechanisms 30 31923609
2016 Crosstalk between ATF4 and MTA1/HDAC1 promotes osteosarcoma progression. Oncotarget 30 26797758
2023 Collateral lethality between HDAC1 and HDAC2 exploits cancer-specific NuRD complex vulnerabilities. Nature structural & molecular biology 29 37488358
2017 USP19 deubiquitinates HDAC1/2 to regulate DNA damage repair and control chromosomal stability. Oncotarget 29 27517492
2021 SNP rs4971059 predisposes to breast carcinogenesis and chemoresistance via TRIM46-mediated HDAC1 degradation. The EMBO journal 28 34459501
2021 BAP1 forms a trimer with HMGB1 and HDAC1 that modulates gene × environment interaction with asbestos. Proceedings of the National Academy of Sciences of the United States of America 28 34815344
2015 Decreased Expression of CoREST1 and CoREST2 Together with LSD1 and HDAC1/2 during Neuronal Differentiation. PloS one 28 26111147
2020 SLC14A1 prevents oncometabolite accumulation and recruits HDAC1 to transrepress oncometabolite genes in urothelial carcinoma. Theranostics 27 33052246
2015 Inactivation of HDAC1 or HDAC2 induces gamma globin expression without altering cell cycle or proliferation. American journal of hematology 27 25808664
2019 Role of HDAC1 in the progression of gastric cancer and the correlation with lncRNAs. Oncology letters 26 30867763
2017 Differential HDAC1 and 2 Recruitment by Members of the MIER Family. PloS one 26 28046085
2021 Nonredundant, isoform-specific roles of HDAC1 in glioma stem cells. JCI insight 25 34494550
2019 HDAC1 and HDAC2 independently regulate common and specific intrinsic responses in murine enteroids. Scientific reports 25 30926862
2023 HDAC1 is Involved in Neuroinflammation and Blood-Brain Barrier Damage in Stroke Pathogenesis. Journal of inflammation research 24 37745794
2018 HDAC1 overexpression enhances β-cell proliferation by down-regulating Cdkn1b/p27. The Biochemical journal 24 30322885
2021 EGFR phosphorylates HDAC1 to regulate its expression and anti-apoptotic function. Cell death & disease 23 33976119
2021 MCM5 Aggravates the HDAC1-Mediated Malignant Progression of Lung Cancer. Frontiers in cell and developmental biology 23 34409025
2022 HDAC1 Regulates Neuronal Differentiation. Frontiers in molecular neuroscience 22 35095417
2021 HDAC1 deregulation promotes neuronal loss and deficit of motor function in stroke pathogenesis. Scientific reports 22 34381129
2019 Expression of Histone Deacetylases HDAC1 and HDAC2 and Their Role in Apoptosis in the Penumbra Induced by Photothrombotic Stroke. Molecular neurobiology 22 31493239
2018 HDAC1 Substrate Profiling Using Proteomics-Based Substrate Trapping. ACS chemical biology 22 30421914
2025 Inflammation-driven NF-κB signaling represses ferroportin transcription in macrophages via HDAC1 and HDAC3. Blood 21 39656097
2025 Exosomal circ_0006896 promotes AML progression via interaction with HDAC1 and restriction of antitumor immunity. Molecular cancer 21 39762891
2022 The clock component OsLUX regulates rice heading through recruiting OsELF3-1 and OsELF4s to repress Hd1 and Ghd7. Journal of advanced research 21 35940490
2022 FRA1:c-JUN:HDAC1 complex down-regulates filaggrin expression upon TNFα and IFNγ stimulation in keratinocytes. Proceedings of the National Academy of Sciences of the United States of America 21 36067301
2017 YY1 promotes HDAC1 expression and decreases sensitivity of hepatocellular carcinoma cells to HDAC inhibitor. Oncotarget 21 28489564
2021 JAK-STAT Pathway Inhibition Partially Restores Intestinal Homeostasis in Hdac1- and Hdac2-Intestinal Epithelial Cell-Deficient Mice. Cells 20 33498747
2017 Modulations of DNMT1 and HDAC1 are involved in the OTA-induced cytotoxicity and apoptosis in vitro. Chemico-biological interactions 20 29080797
2024 The histone deacetylase HDAC1 controls dendritic cell development and anti-tumor immunity. Cell reports 19 38829740
2021 Epigenetic targeting of SLC30A3 by HDAC1 is related to the malignant phenotype of glioblastoma. IUBMB life 19 33715270
2020 The inhibition of microRNA-326 by SP1/HDAC1 contributes to proliferation and metastasis of osteosarcoma through promoting SMO expression. Journal of cellular and molecular medicine 19 32743904
2019 MiR-761 inhibits colorectal cancer cell proliferation and invasion through targeting HDAC1. Die Pharmazie 19 30782261
2017 Immunoexpression of HDAC1, HDAC2, and HAT1 in actinic cheilitis and lip squamous cell carcinoma. Oral diseases 19 28107582
2014 HDAC1 controls CD8+ T cell homeostasis and antiviral response. PloS one 19 25333902
2017 DDX23-Linc00630-HDAC1 axis activates the Notch pathway to promote metastasis. Oncotarget 18 28473661
2025 Rapid degradation of histone deacetylase 1 (HDAC1) reveals essential roles in both gene repression and active transcription. Nucleic acids research 17 39704107
2023 HDAC1 and HDAC6 are essential for driving growth in IDH1 mutant glioma. Scientific reports 17 37528157
2023 HDAC1 inhibits beige adipocyte-mediated thermogenesis through histone crotonylation of Pgc1a/Ucp1. Cellular signalling 17 37640195
2018 Clinicopathological features and prediction values of HDAC1, HDAC2, HDAC3, and HDAC11 in classical Hodgkin lymphoma. Anti-cancer drugs 17 29481474
2022 LncRNA SNHG1 regulates neuroblastoma cell fate via interactions with HDAC1/2. Cell death & disease 16 36130928
2020 HDAC1 and HDAC2 regulate anti-inflammatory effects of anesthetic isoflurane in human monocytes. Immunology and cell biology 16 31950542
1996 Isolation and mapping of a human gene (RPD3L1) that is homologous to RPD3, a transcription factor in Saccharomyces cerevisiae. Cytogenetics and cell genetics 16 8646880

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