Search Results (989)

Yeast +1 nucleosomes positioned at transcription start sites must be reorganized to allow transcription initiation. Nucleosome reorganization involves multiple factors including histone chaperone FACT (FAcilitates Chromatin Transcription), histone acetylation, and histone variant H2A.Z; however, the mechanism of this process is not fully understood. Here we investigated nucleosome unfolding in the presence of these factors by combining biochemical assays with single-particle Förster resonance energy transfer (spFRET) microscopy. The presence of the H3:K56Ac mimic (H3:K56Q) alone or together with H2A.Z (but not H2A.Z alone) facilitates the Nhp6-dependent unfolding of nucleosomes by FACT. In contrast to canonical nucleosomes, the unfolding of nucleosomes with the studied variant histones promotes the eviction of core histones from nucleosomal DNA. Furthermore, H2A.Z alone or in synergy with H3:K56Q facilitates transcription through a nucleosome as efficiently as FACT facilitates transcription through canonical nucleosomes. The data suggest that FACT, together with H3:K56 acetylation and H2A.Z, unfold promoter nucleosomes and participate in the eviction of histones to increase the accessibility of the transcription start site, thereby stimulating transcription initiation and possibly early elongation. Full article

Background/Objectives: Histone acetylation regulates gene expression and plays a key role in cancer pathophysiology. Nanotherapeutics are known to modulate histone acetylation and influence cancer progression. This systematic scoping review examines the effects of nanotherapeutics on histone acetylation enrichment across multiple cancers. Methods: A systematic search of Embase, PubMed/MEDLINE, Scopus, and Web of Science was conducted in accordance with the PRISMA 2020 statement. A total of 13 studies were included. Data were analyzed and visualized in R, and risk of bias was assessed with ToxRTool (OSF Registration: 10.17605/OSF.IO/E643S). Results: Nanotherapeutics were most commonly evaluated against breast (21.4%), prostate (21.4%), pancreatic (14.3%), and bladder (14.3%) cancers. Primary nanomaterials used in the synthesis of nanotherapeutics included poly(lactic-co-glycolic acid) (25.0%), gold (21.4%) and arsenic oxide (21.4%) nanoparticles. Studied histone acetylation marks included H3K9ac, H3K14ac, H3K27ac and H4K16ac. Treatment with nanotherapeutics increased histone H3 and H4 acetylation enrichment, particularly H3K14ac in colorectal and prostate cancers and H4K16ac in ovarian cancer. Conversely, gold-based nanotherapeutics decreased H3K9ac and H3K14ac enrichment in breast cancer. The optimal concentration for most nanotherapeutics was ≤25 µM, with PpIX-FFYSV showing the strongest anticancer effect (viability <25%). Across four preclinical studies (n = 58), treatment with the nanotherapeutics reduced tumor size to less than 50% of control in 64% of animals (95% CI: 21–92%, I² = 63.8%). Altered histone acetylation was associated with differential expression of CDKN1A, HSPA1, SREBF2 and TGFB. Conclusions: The evidence demonstrates that nanotherapeutics can alter histone acetylation patterns by modulating EP300/CBP, GCN5 and HDAC, preventing cancer progression and invasion. Full article

Phytochemicals are plant-derived bioactive compounds with antioxidant, anti-inflammatory, and epigenetic modulatory effects that may contribute to the prevention and management of chronic diseases. This review synthesizes recent evidence on the molecular mechanisms through which phytochemicals influence oxidative stress, inflammatory signaling, and epigenetic regulation. A targeted literature search of the PubMed and Web of Science databases (2015–2025) identified over 400 experimental and review studies investigating phytochemicals with documented antioxidant and epigenetic activities. Eligible articles were selected based on relevance to oxidative stress, inflammation, and DNA or histone modification pathways in chronic diseases. Data were qualitatively analyzed to highlight mechanistic links between redox balance, transcriptional regulation, and disease modulation. The results indicate that several phytochemicals, including hesperidin, phloretin, lycopene, and silybin, modulate signaling cascades—NF-κB, Nrf2, and PI3K/Akt—while also influencing DNA methylation and histone acetylation to restore gene expression homeostasis. Despite strong in vitro and in vivo evidence, translation to clinical practice remains limited by low bioavailability, lack of standardized formulations, and insufficient human trials. Future research should prioritize integrative study designs linking molecular mechanisms to clinical endpoints. Understanding the epigenetic actions of phytochemicals may guide the development of nutraceutical strategies for chronic disease prevention. Full article

Major Depressive Disorder (MDD) remains a leading cause of disability worldwide, perpetuated by an incomplete understanding of its pathophysiology and the limited efficacy of conventional antidepressants. Historically, research has focused on neuron-centric models, particularly the monoamine hypothesis. However, the field is now recognizing the critical role of glial cells such as astrocytes, microglia, and oligodendrocytes, establishing them as key contributors to the molecular basis of depression. Rather than serving solely supportive roles, these cells actively modulate neuroinflammation, synaptic plasticity, neurotransmitter homeostasis, and metabolic regulation, processes disrupted in MDD. We discuss how stress-induced epigenetic modifications such as histone acetylation, methylation, and DNA methylation are linked to alterations in astrocytic glutamate transport, microglial inflammatory states, and oligodendrocyte-mediated myelination. Special emphasis is placed on the concept of glial transcriptional plasticity, whereby environmental adversity induces durable and cell type specific gene expression changes that underlie neuroinflammation, excitatory–inhibitory imbalance, and white matter deficits observed in MDD. By integrating findings from postmortem human tissue, single-cell omics, and stress-based animal models, this review highlights converging molecular mechanisms linking stress to glial dysfunction. We further outline how targeting glial transcriptional regulators may provide new therapeutic avenues beyond conventional monoaminergic approaches. Full article

Heavy metal and metalloid stress, particularly from toxic elements like cadmium (Cd), poses a growing threat to plant ecosystems, crop productivity, and global food security. Elevated concentrations of these contaminants can trigger cytotoxic and genotoxic effects in plants, severely impairing growth, development, and reproduction. In recent years, epigenetic mechanisms have emerged as crucial regulators of plant responses to heavy metal stress, offering novel insights and strategies for enhancing plant resilience in contaminated environments. This review synthesises current advances in the field of plant epigenetics, focusing on key modifications such as DNA methylation, histone acetylation and remodelling, chromatin dynamics, and small RNA-mediated regulation. These processes not only influence gene expression under metal-induced stress but also hold promise for long-term adaptation through transgenerational epigenetic memory. Recent developments in high-throughput sequencing and functional genomics have accelerated the identification of epigenetic markers associated with stress tolerance, enabling the integration of these markers into breeding programs and targeted epigenome editing strategies. Special attention is given to cadmium stress responses, where specific epigenetic traits have been linked to enhanced tolerance. As plant epigenomic research progresses, its application in sustainable agriculture becomes increasingly evident offering environmentally friendly solutions to mitigate the impact of heavy metal pollution. This review provides a foundation for future research aimed at leveraging epigenetic tools to engineer crops capable of thriving under metal stress, thereby contributing to resilient agricultural systems and sustainable food production. Full article

The TIP60/NuA4 complex is a large, multifunctional histone acetyltransferase assembly of ~1.7 megadaltons, composed of 17–20 subunits, which plays a central role in epigenetic regulation. Through recognition of H3K4me3 by the ING3 reader, TIP60/NuA4 is recruited to sites of active transcription, where it remodels chromatin to regulate gene expression. Its activities include histone acetylation, histone variant exchange, transcriptional co-activation, and regulation of the cell cycle and apoptosis. In this review, we examine how altered subunit levels or mutations impact the chromatin structure and transcriptional activity, and how these changes influence differentiation across diverse cell types. We emphasize the molecular mechanisms by which TIP60/NuA4 shapes lineage specification, including histone H2A and H4 acetylation by the KAT5 catalytic subunit, H2A.Z incorporation by EP400, and interactions with transcription factors such as MyoD, PPARγ, and Myc. By integrating mechanistic and functional insights, we highlight how TIP60/NuA4 acts as a central epigenetic hub in differentiation and contributes to proper developmental transitions. Full article

Triple-negative breast cancer (TNBC) remains a leading cause of cancer-related mortality in women, characterized by its aggressive nature and limited therapeutic options. TNBC is defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, which excludes patients from targeted endocrine and HER2-directed therapies, contributing to poor prognosis. This study investigates BKS-112, a potent histone deacetylase 6 (HDAC6) inhibitor, for its anticancer activity against TNBC using MDA-MB-231 cells. We assessed HDAC protein expression and their prognostic implications, alongside in vitro experiments analyzing cell viability, apoptosis, autophagy, and colony formation. BKS-112 exhibited dose- and time-dependent reductions in cell viability, significant morphological alterations, and decreased colony formation. The compound increased the acetylation of histones H3, H4, and α-tubulin while downregulating HDAC6 expression and activity. Additionally, BKS-112 reduced cell migration, demonstrating anti-metastatic potential. It induced G1 phase cell cycle arrest and modulated key regulators, including cyclins and cyclin-dependent kinases (CDKs). Apoptosis was promoted through mitochondrial pathways, evidenced by changes in Bcl-2, Bax, and caspase activation. BKS-112 also elevated reactive oxygen species (ROS) levels, affecting apoptosis-related PI3K/AKT signaling. Autophagy was triggered by upregulating LC3 and Atg-7 expression. Collectively, these findings suggest that BKS-112 exerts robust anticancer effects by inducing cell cycle arrest, apoptosis, and autophagy, highlighting its therapeutic promise for TNBC treatment. Full article

Colletotrichum gloeosporioides causes anthracnose on a wide range of plants, resulting in serious economic losses worldwide. However, the molecular mechanisms underlying its pathogenicity still remain largely unknown. In the past 20 years, the importance of acetylation/deacetylation modification in the pathogenicity of phytopathogens has already been highlighted, but how it functions in C. gloeosporioides is obscure. Here, we identified and functionally characterized a histone acetyltransferase CgHat1 in C. gloeosporioides. As suspected, CgHat1 is localized to the nucleus and regulates the acetylation levels of histone H4K5 and H4K12. Targeted gene deletion revealed that CgHat1 plays crucial roles in growth, colony pigmentation, and conidiation. Furthermore, we provided evidence showing that ΔCghat1 mutant is defective in conidial germination, appressorial formation, and response to endoplasmic reticulum (ER) stress. These combined effects lead to the decreased pathogenicity of ΔCghat1 mutant. Our studies not only firstly shed light on the pleiotropic roles of histone acetyltransferase in C. gloeosporioides, but also offer a potential fungicide target for anthracnose control. Full article

Background/Objectives: Tau protein, a central player in Alzheimer’s disease (AD) pathology, is classically known for its role in microtubule stabilisation. However, accumulating evidence indicates that tau also localises to the neuronal nucleus, particularly the nucleolus, where it may regulate chromatin organisation and transcription. In this study, we investigated whether different phosphorylation states of nuclear tau display age- and disease-dependent patterns, with a specific focus on the AT8 epitope (phospho-Ser202/Thr205). Methods: We analysed nuclear tau epitopes (Tau-1, AT8, PHF1, T181, and S262) by indirect immunofluorescence in SK-N-BE neuroblastoma cells under proliferative and retinoic acid-induced differentiated conditions and in post-mortem hippocampal CA1 neurons from foetal, young, aged, and AD brains. Other functional markers (UBTF, Ki67, fibrillarin and acetylated histone H4) were used to assess nuclear organisation and function. Results: Compared with the other epitopes, AT8 was unique in showing dynamic nuclear localisation: absent in proliferating cells but present after differentiation, abundant in young neurons, and significantly reduced in aged and AD samples. Nuclear AT8 co-localised with Ki67, and its decline was associated with neuronal cell cycle re-entry and nucleolar disorganisation. Conclusions: Among multiple nuclear tau epitopes, AT8 was the only one displaying age- and disease-related changes, and its reduction during ageing and AD correlates with nuclear stress, aberrant cell cycle activity, and neuronal vulnerability. Loss of nuclear AT8 may therefore represent an early marker of dysfunction in ageing and AD brains. Full article

(Background) Retinoblastoma is the most common intraocular malignancy in childhood, primarily caused by mutations in the RB1 gene. However, increasing evidence highlights the significant role of epigenetic mechanisms, particularly DNA methylation and histone acetylation, in tumor initiation and progression. This review aims to summarize and critically assess recent findings on how DNA methylation and histone acetylation contribute to the pathogenesis of retinoblastoma, and to explore their potential role as diagnostic biomarkers and therapeutic targets. (Methods) We searched the databases PubMed, Scopus, and ScienceDirect following PRISMA guidelines. Eligible studies were English-language, open-access articles published within the last ten years, including cohort studies, research articles, and case reports. After rigorous screening, 18 studies were included in the final analysis. (Results) Aberrant DNA methylation was found to inactivate tumor suppressor genes (RB1, RASSF1A, p16INK4A, MGMT) and promote oncogenesis through hypermethylation of regulatory elements. Similarly, histone acetylation’s dysregulation contributed to chromatin remodeling and overexpression of oncogenic factors such as SYK, GALNT8, and lincRNA-ROR. Elevated histone deacetylase (HDAC) activity was also linked to tumor cell proliferation, metastasis, and treatment resistance. Epigenetic inhibitors targeting these pathways demonstrated promising therapeutic potential. (Conclusions) DNA methylation and histone acetylation play a crucial role in the epigenetic regulation of genes implicated in retinoblastoma. Their dysregulation promotes tumorigenesis, and targeting these mechanisms represents a promising avenue for novel diagnostic and therapeutic strategies in pediatric oncology. Full article

Specific expression of genes is fundamental for defining the identity and the functional state of cells. Sequence-specific transcription factors interpret the information contained in DNA sequence motifs and recruit cofactors to modify chromatin and control RNA polymerases. This multi-step process typically involves several transcription factors and cofactors with different enzymatic activities. Post-translational modifications (PTMs) of histones are one key mechanism to control chromatin structure and polymerase activity and thus gene transcription. The methylation of histone H3 at lysine 4 (H3K4) is a modification of accessible chromatin, including enhancers and promoters, and also sites of recombination and some forms of DNA damage. H3K4 methylation is catalyzed by six lysine methyltransferase complexes, referred to as KMT2 or COMPASS-like complexes. These are important in processes related to transcription and contribute to recombination in T and B cells. PRDM9 and ASH1L are H3K4 methyltransferases involved in meiotic recombination and DNA repair, respectively. In transcription, H3K4 mono- and tri-methylation are located at enhancers and promoters, respectively. These modifications, either alone or in combination with other histone PTMs, provide binding sites for transcriptional cofactors. Through these sites, H3K4 methylation affects chromatin accessibility and histone PTMs, typically resulting in a favorable environment for transcription. H3K4 tri-methylation also recruits and regulates RNA polymerase II (RNAPII) complexes, which interact with KMT2 complexes, generating positive feedforward loops to promote transcription. Thus, H3K4 methylation has broad activities that are key to different chromatin-associated processes. Full article

Cancer-associated fibroblasts (CAFs) are a key constituent of the tumor microenvironment. CAFs may affect the development of tumor cells. The critical role of CAFs in the tumor microenvironment is linked to their epigenetic modifications, as a stable yet reversible regulation of cellular phenotypes. Current evidence indicates that their formation and function are closely linked to epigenetic mechanisms. Existing research indicates that the epigenetic alteration abnormalities are triggered by metabolic cues and stabilize the acquired phenotype of CAFs. This process is associated with transcriptional changes and patient outcomes in various tumors, providing a biological rationale and translational potential for reprogramming CAFs. Understanding of epigenetic modifications in CAFs remain insufficient, while DNA methylation in CAFs can alter CAF states through multiple pathways and thereby influence tumor progression. It is necessary to investigate the unique, identifiable epigenetic signatures of CAF. As an epigenetic reader couple histone acetylation to high-output oncogenic transcription; meanwhile, noncoding RNAs modulate CAF formation and therapeutic responses via bidirectional crosstalk between tumor cells and stroma. The interactions between different epigenetic modifications and their underlying regulatory logic may play a crucial role in developing new therapeutic strategies. This review focuses on the roles of DNA methylation, histone acetylation, and enhancer reprogramming in CAFs. Full article

Plants have evolved a complex, multilayered immune system that integrates molecular recognition, signaling pathways, epigenetic regulation, and small RNA-mediated control. Recent studies have shown that DNA-level regulatory mechanisms, such as RNA-directed DNA methylation (RdDM), histone modifications, and chromatin remodeling, are critical for modulating immune gene expression, allowing for rapid and accurate pathogen-defense responses. The epigenetic landscape not only maintains immunological homeostasis but also promotes stress-responsive transcription via stable chromatin modifications. These changes contribute to immunological priming, a process in which earlier exposure to pathogens or abiotic stress causes a heightened state of preparedness for future encounters. Small RNAs, including siRNAs, miRNAs, and phasiRNAs, are essential for gene silencing before and after transcription, fine-tuning immune responses, and inhibiting negative regulators. These RNA molecules interact closely with chromatin features, influencing histone acetylation/methylation (e.g., H3K4me3, H3K27me3) and guiding DNA methylation patterns. Epigenetically encoded immune memory can be stable across multiple generations, resulting in the transgenerational inheritance of stress resilience. Such memory effects have been observed in rice, tomato, maize, and Arabidopsis. This review summarizes new findings on short RNA biology, chromatin-level immunological control, and epigenetic memory in plant defense. Emerging technologies, such as ATAC-seq (Assay for Transposase-Accessible Chromatin using Sequencing), ChIP-seq (Chromatin Immunoprecipitation followed by Sequencing), bisulfite sequencing, and CRISPR/dCas9-based epigenome editing, are helping researchers comprehend these pathways. These developments hold an opportunity for establishing epigenetic breeding strategies that target the production of non-GMO, stress-resistant crops for sustainable agriculture. Full article

Polyamines are polycationic compounds present in all living cells that exert functions at different levels in the metabolism. They bind to DNA and RNA and modulate DNA replication and gene expression. Some of these regulatory effects are exerted by promoting condensation of nucleosomes, a mechanism closely connected with epigenetic modification by histone methylation and acetylation. The polyamines 1,3-diaminopropane and spermidine induce expression of the global regulator LaeA and increase by several folds the formation of the α-NAC transcriptional co-activator, a subunit of the nascent polypeptide-associated complex. The global regulator LaeA controls the switch from primary growth to secondary metabolite production and differentiation when an essential nutrient in the growth medium becomes limiting. α-NAC exerts significant control over the biosynthesis of secondary metabolites and fungal pathogenicity on plants. When purified α-NAC protein is added to a tomato host plant, it induces plant resistance to fungal infections and triggers the development of system-acquired resistance in other plants. Spermidine extends the life of yeast cells and prolongs the half-life of penicillin gene transcripts in Penicillium chrysogenum. This article discusses advances in the basis of understanding the mechanism of plant–fungi interaction and the effect of small fungal metabolites and epigenetic modifiers in this interaction. Full article

We have previously established that bexarotene, a clinically approved agonist of retinoid X receptor (RXR), promotes the differentiation and fusion of skeletal myoblasts. We have also analyzed the genomic programs underlying rexinoid-enhanced myogenic differentiation to identify novel regulatory pathways. As such, we observed a significant upregulation of a transcript encoding a predicted transmembrane protein, Tmem182, during C2C12 myoblast differentiation. Despite the documentation of Tmem182 expression in skeletal muscles, its regulation had yet to be explored. Here, we show that Tmem182 gene expression is markedly augmented in early myoblast differentiation and further enhanced by RXR signaling. In addition, Tmem182 expression is specific to muscle tissues and related to muscle master regulator MyoD. We found that MyoD and histone acetyltransferase p300 are bound to the Tmem182 promoter, and Tmem182 expression is p300-dependent. Thus, our data display a putative epigenetic signature associated with p300 and histone acetylation in rexinoid-responsive locus activation and transcription of myogenic targets. Full article