Ask about this productRelated genes to: HDAC1 antibody
- Gene:
- HDAC1 NIH gene
- Name:
- histone deacetylase 1
- Previous symbol:
- RPD3L1
- Synonyms:
- HD1, GON-10, KDAC1
- Chromosome:
- 1p35.2-p35.1
- Locus Type:
- gene with protein product
- Date approved:
- 1996-11-15
- Date modifiied:
- 2019-02-19
Related products to: HDAC1 antibody
Related articles to: HDAC1 antibody
- Efficient skeletal muscle contraction requires tight mechano-metabolic coupling, a process regulated by AMP-activated protein kinase (AMPK). Duchenne muscular dystrophy (DMD) is characterized by aberrant AMPK activation and disrupted metabolic signaling. This study investigates the expression and regulation of the LKB1-STRADα-MO25 heterotrimeric complex, the primary upstream activator of AMPK, in DMD models. We analyzed muscles from dystrophic mice (BL10 mdx and D2 mdx) and patient-derived cells and found significant downregulation of the LKB1 complex across all disease stages in the DMD models, a defect not observed in an amyotrophic lateral sclerosis model. Treatment with the broad-spectrum HDAC inhibitor vorinostat effectively restored LKB1 expression at both transcript and protein levels in D2 mdx mice. This restoration was mechanistically linked to downregulation of miR-451, miR-195, and miR-17, which function as post-transcriptional repressors of LKB1. Conversely, the selective HDAC1/2 inhibitor Rodin-A increased Lkb1 mRNA but failed to rescue protein levels or alter miRNA expression. Our data identify the axis LKB1-STRADα-MO25 as a critical regulatory node that is disrupted in DMD, but remains responsive to epigenetic modulation. These findings suggest that restoring LKB1 activity via HDAC inhibition or miRNA targeting may represent a therapeutic avenue to address dystrophic muscle dysfunction. - Source: PubMed
Boccanegra BrigidaTulimiero LisamauraQuarta RaffaellaConte ElenaLicandro Simonetta AndreaDecio AlessandraLenti RobertaLadisa AlbertoDinoi GiorgiaCarbone GaiaClaudione LetiziaCamerino Giulia MariaPierno SabataMantuano PaolaCappellari OrnellaFossati GianlucaSteinkühler ChristianDe Luca Annamaria - Little is known about why Foxp3⁺ regulatory T (Treg) cells require at least three HDAC1/HDAC2-containing chromatin-remodeling complexes (NuRD, Sin3 and CoREST), or whether selective disruption of these complexes can be exploited to enhance antitumor immunity. Here, we investigated the role of chromodomain helicase DNA-binding protein 4 (CHD4), the ATP-dependent remodeling subunit of the NuRD complex, in Treg biology. Conditional deletion of Chd4 in Foxp3⁺ Tregs resulted in severe systemic autoimmunity and early lethality, accompanied by reduced Foxp3 expression, impaired Treg suppressive function, and loss of Treg lineage stability. Transcriptomic analyses demonstrated that CHD4 deficiency closely phenocopied Hdac2 deletion, whereas quantitative proteomic analyses revealed that CHD4 assembles into highly conserved NuRD complexes in both Treg and conventional CD4⁺ T cells. These findings indicate that the selective dependence of Tregs on CHD4 does not arise from the formation of lineage-specific protein complexes but rather from the unique epigenetic program maintained by CHD4-containing chromatin-remodeling complexes that is required for Treg differentiation and stability. Using a novel cellular target-engagement platform, we identified CH41, a potent small-molecule inhibitor of CHD4 that recapitulated the effects of genetic CHD4 ablation on Treg function. Pharmacological inhibition of CHD4 impaired intratumoral Treg accumulation and function and significantly inhibited the growth of lung and hepatocellular carcinomas in immunocompetent, but not immunodeficient, mice, without inducing systemic autoimmunity. Collectively, our findings identify CHD4 as a critical epigenetic regulator of Treg lineage stability and establish pharmacological targeting of the CHD4/NuRD axis as a promising strategy to selectively disrupt tumor-associated Tregs and enhance antitumor immunity. - Source: PubMed
Publication date: 2026/07/31
Xiong YanWang LiqingMinisini MartinaKong FanhuaDi Giorgio ErosAkimova TatianaHorman ShaneBabic IvanNurmemmedov ElmarHancock Wayne W - Benzene exposure induces hematotoxicity, partially through disrupted DNA damage repair. SIRT6 is a key regulator of both DNA repair and metabolism. While its connection to metabolic reprogramming and novel lactylation modifications in benzene toxicity remains unknown. Herein, we found decreased SIRT6 expression in the peripheral WBCs of benzene-exposed workers. Furthermore, mediation analysis identified SIRT6, p16, and serum γ-H2AX levels as mediators of the inverse relationship between urinary S-PMA and WBC counts. In vitro, benzoquinone (BQ) suppressed SIRT6, enhanced glycolysis and lactate production, and induced DNA double-strand breaks (DSBs) and senescence. SIRT6-knockdown models confirmed that SIRT6 deficiency exacerbates benzene-induced increase in glycolysis and lactate accumulation. Crucially, lactate reduction with DCA attenuated DSBs and cellular senescence in bone marrow cells, mitigating hematopoietic damage. Mechanistically, we identified PRMT5 as a novel lactylation target of SIRT6 at lysine 240 (K240), a process that SIRT6 regulated through the lactyltransferase TIP60 and delactylase HDAC1. Functional studies in K240-mutant cells demonstrated that blocking lactylation at this site alleviated BQ-induced DSBs and senescence. Our findings establish that SIRT6 deficiency drives a lactate-fuelled lactylation of PRMT5 at K240, impairing DNA repair and promoting hematopoietic stem cell senescence caused by benzene. This work elucidates a previously unrecognized metabolic-epigenetic axis in benzene toxicity and highlights the therapeutic potential of targeting glycolytic flux or specific lactylation events to combat chemical-induced hematological damage. - Source: PubMed
Publication date: 2026/08/18
Sun RongliXu KaiLi XiaoqinHuang JiaweiWang DaqinPu YuepuZhang Juan - Mounting evidence implicates long non-coding RNA cancer susceptibility candidate 19 (CASC19) in the pathogenesis of diverse malignancies. However, its functional role and molecular mechanisms in gastric cancer (GC) remain elusive. Herein, we identified a novel 717-bp transcript isoform of CASC19 in GC cells. This study aimed to delineate the biological functions and underlying mechanisms of this novel CASC19 transcript in GC pathogenesis. CASC19 was significantly upregulated in GC tissues and cell lines, correlating with adverse clinicopathological features and poor prognosis in GC patients. Functional investigations demonstrated that CASC19 overexpression potentiated GC cell proliferation, metastasis, and epithelial-mesenchymal transition, whereas CASC19 knockdown attenuated these malignant phenotypes and suppressed tumorigenesis in xenograft models. Mechanistically, CASC19 functioned as a molecular scaffold by recruiting histone deacetylase 1 (HDAC1) to the nucleophosmin 1 (NPM1) promoter. This recruitment sustained H3K27 deacetylation, thereby transcriptionally repressing NPM1 promoter activity and accelerating gastric carcinogenesis. Crucially, Depletion of HDAC1 or NPM1 partial rescued CASC19-mediated oncogenic effects. Intriguingly, the transcription factor c-Myc was found to transcriptionally activate CASC19 through direct binding to its promoter region. Collectively, our findings indicate that the c-Myc-CASC19/HDAC1-NPM1 axis acts as a potential prognostic biomarker candidate for GC and may represent a therapeutic vulnerability worthy of future investigation. - Source: PubMed
Publication date: 2026/08/18
Wang Wen-JieGuo Chang-AnWu Ming-ZhongShan Xu-HuLiu DongMa BiaoWang Wen-AnXia Tian-HongCao Xiao-MengYuan Shao-BinWei Deng-WenYan LongLiu Hong-BinHuang Ze-PingLiu Hai-Peng - Glioblastoma, the most prevalent and highly aggressive primary brain tumor, is characterized by high clinical recurrence rates and significant resistance to conventional therapies, highlighting the need for innovative targeted agents to address current treatment limitations. This study employed an integrated computational and experimental strategy to identify novel iodo-phenanthroimidazole derivatives (compounds 1-3). Compound 3 was identified as a lead candidate that inhibits HDAC1 and may trigger autophagy, thereby suppressing glioblastoma progression. Molecular docking and molecular dynamics simulations indicated stable interactions between compound 3 and the HDAC1 catalytic site (estimated binding energies of -7.75 and - 7.74 kcal/mol), with a notable halogen bond between the iodine atom and Asp104. The phenanthroimidazole scaffold was proposed as a potential zinc-binding group (ZBG) for HDAC1 inhibition. Biophysical validation using isothermal titration calorimetry (ITC) confirmed submicromolar binding affinity (Kd = 1.04 × 10 M, ΔH = -91.24 kJ·mol). In vitro evaluation demonstrated potent inhibition of U87-MG glioblastoma cell proliferation (IC = 0.23 μM), and flow cytometric analysis indicated concomitant cell cycle arrest at both G2/M and S phases. Transmission electron microscopy revealed autophagic vacuoles containing damaged mitochondria, and immunofluorescence showed an increased LC3-II/LC3-I ratio. Together with the observed loss of mitochondrial membrane potential and ATP depletion, these findings are consistent with the induction of a mitophagy-like process. Using an in vivo zebrafish orthotopic glioblastoma model, the lead compound demonstrated blood-brain barrier penetration and effectively suppressed tumor growth and U87-MG cell metastasis. This work highlights the potential of iodo-phenanthroimidazole derivatives as a novel therapeutic strategy for glioblastoma. The data support a model in which HDAC1 inhibition is associated with mitochondrial dysfunction and mitophagy, contributing to tumor suppression. - Source: PubMed
Publication date: 2026/08/12
Shi XiaomeiLiang JiangboWu ZhuoyanShe MengjiaoLiu YanZhu ChunguangFang LingDong RanxiWu QiongMei Wenjie