Ask about this productRelated genes to: HDAC4 antibody
- Gene:
- HDAC4 NIH gene
- Name:
- histone deacetylase 4
- Previous symbol:
- BDMR
- Synonyms:
- KIAA0288, HDAC-A, HDACA, HD4, HA6116, HDAC-4
- Chromosome:
- 2q37.3
- Locus Type:
- gene with protein product
- Date approved:
- 2000-11-28
- Date modifiied:
- 2015-09-11
Related products to: HDAC4 antibody
Related articles to: HDAC4 antibody
- Skeletal muscle atrophy is a secondary complication in the aetiology of injury and chronic disease. Identifying mechanisms that control muscle mass is necessary to characterise atrophy and develop prevention strategies. We aimed to integrate transcriptomic and epigenomic data to identify key regulatory pathways controlled by promoter DNA methylation during muscle unloading. Twenty-one healthy men (20-40 years) completed a 4-week standardised exercise programme prior to a 14-day knee brace immobilisation with dietary control. Skeletal muscle mass and strength were assessed before and after immobilisation and biopsies were collected (m. vastus lateralis) before, at 3 days, and at completion at 14 days. RNA and DNA were isolated and analysed using Illumina RNA sequencing and DNA methylation 850K EPIC BeadChips. The 14-day immobilisation decreased muscle mass (∼9%; P < 0.0001) and strength (∼16%; P < 0.0001). At 3 days, most biological processes (BPs) were upregulated/hypomethylated (157 gene sets); upregulated BPs included cell signalling and protein ubiquitination and downregulated BPs included metabolism. After 14 days, BPs were predominantly downregulated/hypermethylated, including translation and ribosome biogenesis. Across both time points, HDAC4, GADD45A and CHRNA1 emerged as methylation-regulated candidate mediators of atrophy. HDAC4 and GADD45A showed strong correlations primarily at day 3, and CHRNA1 remained significant at both time points, extending prior observations in animals to human skeletal muscle. We have characterised changes in gene expression related to hypo- and hyper-methylation during muscle unloading in humans. These data extend our understanding of the regulatory processes that occur during skeletal muscle atrophy that, at the individual gene level, may be useful in developing strategies for reducing muscle wasting. - Source: PubMed
Publication date: 2026/08/24
Thompson Jamie-Lee MDoering Thomas MBudiono Boris PMackenzie-Shalders Kristen LAshton Kevin JDunn Paul JCoffey Vernon G - This chapter pulls together current research on how HDAC shuttling between the nucleus and cytoplasm affects neurodegenerative diseases like Alzheimer's, Parkinson's, Huntington's, and epilepsy. It takes a close look at why these shifts in HDAC localization matter so much in brain disease and its implications for new treatments. Histone deacetylases (HDACs) are a big deal when it comes to gene regulation in the brain. They play key roles in both neurodegeneration and the brain's ability to adapt, working inside the nucleus and out in the cytoplasm. This chapter unpacks the molecular mechanisms behind HDAC trafficking-how they move around-highlights the different roles of HDAC isoforms, and compares localization-specific effects. It digs into how HDACs impact protein aggregation and synaptopathies. Some findings stand out: HDAC4 and HDAC1 are tightly controlled by phosphorylation signals, which change their cellular localization and influence neuronal mortality. For example, HDAC6 is majorly involved in cellular trafficking and clearing protein aggregates, whereas HDAC4 aggregation in the nucleus is responsible for driving neuronal toxicity. If HDAC1 undergoes nuclear export, it interacts with motor proteins to impact mitochondrial transport. Drugs that block HDAC6 look promising in preclinical models-they help restore neuronal transport systems and clear protein aggregation. Moving HDAC4 out of the nucleus seems to support better synaptic function and motor skills. As a general rule, HDAC accumulation in the nucleus shuts down genes that keep neurons alive, but keeping them in the cytoplasm helps preserve connections between neurons. You'll also find thorough, practical advice on how to study HDACs in brain research-covering everything from enzyme assays and cell experiments to live animal models, plasticity tracking, drug testing, and data analysis. A major innovation featured here is using CRISPR-based tricks to control exactly where HDACs go inside cells: forced targeting using dCas9 fusions, editing natural localization signals, and even using optogenetics for precise on-demand control. In short, the chapter is a hands-on guide for anyone trying to unravel HDAC mechanisms in diseases like Alzheimer's, Parkinson's, Huntington's, or in studies of brain plasticity. Some standout methods include tracking HDAC localization in the cells, measuring how phosphorylation affects their shuttling, and using HDAC2 inhibitors for cognitive boosts. It also covers isoform-specific approaches in Huntington's models, manipulating HDAC location with CRISPR for deeper insights, and combining live-cell imaging with biochemical and chromatin studies for robust validation. This chapter sheds light on the latest advances, with a strong focus on precision, quantitative results, and translating these findings into real-world applications. - Source: PubMed
Publication date: 2026/07/15
Mehta BhupeshNambiar SinjithaShirke OmkarPandita SatyarthMarkandeya Yogananda S - Skeletal muscle growth in poultry depends on the proliferation and differentiation of skeletal muscle satellite cells (SMSCs), yet the regulatory landscape governing these processes in quail remains poorly defined. In this study, primary SMSCs were isolated from embryonic day 15 quail pectoral muscle and validated by PAX7 immunostaining and MYHC immunostaining following induction of differentiation. rRNA-depleted RNA-seq was performed at three developmental stages: satellite cells after differential adhesion (DA), proliferating myoblasts (GM), and differentiated myotubes after 4 d (DM4). Transcriptome profiling identified 9,728 common genes expressed in three group, with 1,254 genes differentially expressed across all pairwise comparisons. Functional enrichment analyses indicated a coordinated shift from cell cycle progression in proliferating cells to muscle contraction, oxidative phosphorylation, and calcium signaling during differentiation. Short time-series expression miner (STEM) analysis revealed distinct temporal expression patterns, highlighting proliferation-associated regulators (e.g., KDR, PIK3R1, MYF5, MYF6, NOTCH1, and WNT2) and myotube-related genes (e.g., ALDH18A1, HOXC8, TBX5, and EN1) as central nodes within stage-specific networks. In addition, 935 lncRNAs and 13,588 circRNAs were detected, many displaying stage-specific expression patterns. Predicted lncRNA-mRNA interactions and circRNA host gene enrichment implicated these noncoding RNAs in muscle development and metabolic remodeling. A competing endogenous RNA network highlighted miR-466-x and novel-m0255-5p as potential post-transcriptional regulators of muscle-related genes, including VEGFA, HDAC4, MYLK4, and NOX4. These findings provide a comprehensive transcriptomic resource for quail myogenesis and identify candidate coding and noncoding regulators relevant to muscle growth in poultry. - Source: PubMed
Publication date: 2026/08/03
Liu JingJiang HongxiaXiao XiaoyunLiao ZurongWang YuxiangDing ZhenxvanChai XuewenLiu HaodongHuang XvwenWei WenhuaXie YunongLiu LuoyangWang ZikunHu XiaolongLiu SanfengChen BiaoMao Huirong - Heart failure (HF) is a systemic syndrome in which myocardial remodeling and multiorgan dysfunction exacerbate each other. This review focuses on the hepatokine Fetuin-A and the post-translational modification N-myristoylation in HF. Regarding Fetuin-A, we first demonstrated that circulating Fetuin-A levels were significantly lower in HF patients than in control subjects without structural heart disease. This reduction was associated with hepatic hypoperfusion. In a prospective study of 202 HF patients who underwent cardiopulmonary exercise testing, the combination of lower Fetuin-A and impaired exercise tolerance was independently associated with increased risk of cardiac events, suggesting that Fetuin-A could serve as a novel mediator of cardiac-hepatic-peripheral interaction. Regarding N-myristoylation, expression of N-myristoyltransferase 2 (NMT2) was significantly reduced in failing hearts. Cardiac-specific NMT2 knockdown exacerbated cardiac dysfunction, whereas AAV9-mediated NMT2 gene transfer attenuated cardiac remodeling and HF. Click chemistry-based proteomics identified MARCKS as a crucial substrate, and N-myristoylation of MARCKS prevented pathological hypertrophy by promoting its membrane localization, thereby suppressing CaMKII-HDAC4 signaling. These findings indicate that Fetuin-A and NMT2-dependent N-myristoylation play important roles in HF pathophysiology and represent potential novel therapeutic targets. - Source: PubMed
Publication date: 2026/08/13
Tomita YusukeMisaka TomofumiYokokawa TetsuroTakeishi Yasuchika - Co-evolution between viruses and autophagy has led to the emergence of viral strategies that manipulate host endoplasmic reticulum (ER) homeostasis, ultimately promoting viral replication. ER turnover is achieved through selective autophagy, also referred to as ER-phagy, which is regulated by the RETREG1/FAM134B (reticulophagy regulator 1) family of reticulon proteins. Nevertheless, how viruses target RETREG1, a receptor for ER-phagy, remains largely unclear. In this study, we demonstrate that infection with Senecavirus A (SVA), an emerging picornavirus, triggers the cleavage of RETREG1, which functions as a negative regulator of viral replication. By screening viral proteins, we identified the SVA 3C protease (3C[pro]) as the executor of this cleavage event. Detailed mapping revealed that residues Q428, E430, and G431 of RETREG1 are involved in its cleavage by the 3C[pro], and the resulting two fragments fail to suppress viral replication. Furthermore, proteolytic cleavage of RETREG1 by 3C[pro] impairs its ability to relieve ER stress and mediate ITPR1 degradation via RETREG1-dependent ER-phagy. This disruption leads to increased ER calcium (Ca) release and subsequent activation of autophagy through the CAMKK2-PRKAA2-MTOR axis, which ultimately facilitates SVA replication. Taken together, these findings indicate that SVA antagonizes the antiviral function of RETREG1-mediated ER-phagy via its 3C[pro], highlighting RETREG1 as a potential therapeutic target for combating SVA infection. 2-APB: 2-aminoethyl diphenylborinate; PRKAA2/AMPK: protein kinase AMP-activated catalytic subunit alpha 2; ATL3: atlastin GTPase 3; BHK-21: baby hamster kidney-21; CAMKK2: calcium/calmodulin dependent proteinkinase kinase2; CCPG1: cell cycle progression 1; CKAP4/CLIMP63: cytoskeleton associated protein 4; co-IP: co-immunoprecipitation; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole; DM: double mutant; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; eGFP: enhanced green fluorescent protein; ER: endoplasmic reticulum; GFP: green fluorescent protein; HSPA5/GRP78/BiP: heat shock protein family A (Hsp70) member 5; HA: hemagglutinin; HDAC4: histone deacetylase 4; HEK-293T: human embryonic kidney 293T; hpi: hours post-infection; IFA: indirect immunofluorescence assay; ITPR1/IP3R1: inositol 1,4,5-trisphosphate receptor type 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; LIR: LC3-interacting region; mCherry: monomeric cherry; MTOR: mechanistic target of rapamycin kinase; REEP5: receptor accessory protein 5; RETREG1/FAM134B: reticulophagy regulator 1; RTN3: reticulon 3; SD: standard deviation; SEC61B: SEC61 translocon subunit beta; SEC62: SEC62 preprotein translocation factor; SERP1/RAMP4: stress associated endoplasmic reticulum protein 1; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; ST: swine testis; SVA: Senecavirus A; TEM: transmission electron microscopy; TEX264: testis expressed 264, ER-phagy receptor; Tm: tunicamycin; U2OS: human osteosarcoma epithelial cells; UV: ultraviolet; ZVAD-FMK: benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone; μg: microgram; μm: micrometer; μM: micromole. - Source: PubMed
Publication date: 2026/08/11
Mao JingyuYu JuZeng PenghuiYang XiaoyuShi YongyanQu YunjieZhou JianweiWang DedongSong JiangweiWang YongLiu JueHou Lei