Search Results (142)

Salt stress is a major agricultural issue. A promising modern agriculture method is the foliar treatment of zinc oxide nanoparticles (ZnONPs). This approach has shown promise in boosting challenged tomato yields, fruit quality, and leaf extract antibacterial activity against pathogens. A greenhouse experiment was conducted. The previously synthesized and characterized ZnONPs were used to alleviate the harmful effects of NaCl stress. Tomato fruit weight from different treatments was determined, and the gas–liquid chromatography device was used to observe the changes in fatty acid production. The antimicrobial activities of the aqueous and diethyl ether extracts from tomato leaves were determined against six bacterial and six fungal strains. The plants that were salinity-stressed and sprayed with 0.075 and 0.15 g/L ZnONPs showed a better improvement compared to the salinity-stressed plants. Also, the sprayed plants that were not stressed at all showed promising results compared to the control and the other different treatments. Through the process of molecular docking, it was shown that caffeic acid, ferulic acid, p-coumaric acid, sinapic acid, and apigenin-7-glucoside are essential chemicals that possess antibacterial and antifungal effects against the DNA Gyrase inhibitor and the sterol 14-alpha demethylase (CYP51) enzyme, respectively. It is concluded that salt stress can negatively affect the growth, quality, and variant plant features. However, the foliar application of ZnONPs is able to overcome those adverse effects in the stressed plants, and enhance the non-stressed as well. Full article

For decades, 8-oxoguanine (8-oxoG) has been recognized as a pervasive and pro-mutagenic oxidative DNA lesion. In human cells, 8-oxoG is removed from DNA via the base excision repair pathway initiated by 8-oxoguanine–DNA glycosylase (OGG1). However, emerging evidence over the past twenty years suggests a more complex, regulatory role for this DNA modification. Here, we discuss findings that 8-oxoG, particularly when present in gene promoters, can act as a signal to modulate transcription, establishing an 8-oxoG/OGG1 axis in the inflammatory response. Proposed mechanisms include the generation of 8-oxoG during chromatin remodeling processes involving histone demethylases, the recruitment of transcription factors (NF-κB, HIF1α, Myc, SMAD, etc.) by OGG1, and the lesion’s enrichment in guanine-rich sequences prone to forming G-quadruplex structures. The pro-mutagenic nature of 8-oxoG and the lack of dedicated, functionally separate writer and reader proteins challenge its classification as a true epigenetic DNA mark, distinguishing it from canonical epigenetic nucleobases like 5-methylcytosine and 5-hydroxymethylcytosine. On the other hand, 8-oxoG is well suited for the role of a regulatory signal localized to DNA and involved in the cellular response to oxidative stress and the associated physiological stimuli. Full article

Curcuma wenyujin (C. wenyujin) is a Dao-di geoherb. It depends on specific ecological conditions. DNA methylation (5mC) mediates environmental stress responses, regulating both growth and bioactive compound synthesis. This implies epigenetic control of secondary metabolism in C. wenyujin. However, its DNA methylation patterns remain uncharacterized. In this study, we identified five CwC5-MTases and three CwdMTases based on the transcriptome of C. wenyujin. They were responsible for DNA methylation and demethylation, respectively. Structural and integrated phylogenetic analysis classified the five CwC5-MTases into four subfamilies: CwMET, CwCMT, CwDRM, CwDNMT. The three CwdMTases were grouped into the ROS subfamily. Both CwC5-MTases and CwdMTases exhibited the closest evolutionary relationship to their homologs in monocots. Treatment of C. wenyujin seedlings with the DNA methyltransferase inhibitor 5-azacytidine (5-Az) enhanced terpenoid biosynthesis. QPCR analysis demonstrated that this treatment significantly upregulated key biosynthetic genes, with the exception of CwDXS. Subsequent GC detection further revealed a concomitant increase in the accumulation of β-elemene. Furthermore, Methylation-Sensitive Amplification Polymorphism (MSAP) analysis revealed that 5-Az altered global DNA methylation patterns. It primarily induced demethylation events. Finally, we explored the nature of these MSAP bands with altered methylation patterns. Gene identification and the effects of 5-Az on terpenoid biosynthesis and methylation not only elucidate the potential role of DNA methylation in secondary metabolism in C. wenyujin but also provide novel insights into the molecular mechanisms underlying its geoherbalism. This research opens a new avenue for breeding high-yield and stress-tolerant cultivars. Full article

The dynamic regulation of histone methylation is a key mechanism for epigenetic regulation of gene expression. As histone demethylases dependent on divalent iron ions and α-ketoglutarate, the JmjC family plays an important role in plant life activities. Fifty JmjC domain-containing proteins in Arabidopsis thaliana (21) and Brassica rapa (29) are divided into seven distinct groups, with each group endowed with specific functions due to unique structural domains. Some members achieve functional specificity by recognizing specific DNA motifs or interacting with transcription factors, and others exhibit special functional modes due to mutations in their binding sites. By targeting specific genes (such as FLC, FT, WRKY family, PR genes, etc.), they regulate growth and development processes, as well as responses to multiple biotic and abiotic stresses. Focusing on inter-species divergence of Arabidopsis and Brassica, this review summarized JmjC proteins’ structural classification, substrate specificity, and mechanisms, providing a basis for dissecting plant epigenetic networks and guiding Brassica crop breeding desired bolting traits (early or late bolting), high stress resistance and so on. Full article

JC virus (JCV) replicates within the nuclei of glial cells in the human brain and causes progressive multifocal leukoencephalopathy. JCV possesses a small, circular, double-stranded DNA genome, divided into early and late protein-coding regions. The non-coding control region (NCCR) functions bidirectionally for both early and late genes, and the agnogene is located downstream of TCR and upstream of three capsid proteins in the late region. Previously, in cell culture systems, we demonstrated that these capsid proteins accumulate in intranuclear domains known as promyelocytic leukemia nuclear bodies (PML-NBs), where they assemble into virus-like particles (VLPs). To investigate the agnogene’s function, VLPs were formed in its presence or absence, and differential gene expression was analyzed using microarray technology. The results revealed altered expression of histone-modifying enzymes, including methyltransferases (EHMT1, PRMT7) and demethylases (KDM2B, KDM5C, KDM6B), as well as various kinases and phosphatases. Notably, CTDP1, which dephosphorylates the C-terminal domain of an RNA polymerase II subunit, was also differentially expressed. The changes were predominant in the presence of the agnogene. These findings indicate that the agnogene and/or its protein product likely influence epigenetic regulation associated with PML-NBs, which may influence cell cycle control. Consistently, in human brain tissue, JCV-infected glial cells displayed maintenance of a diploid chromosomal complement, likely through G2 arrest. The precise mechanism of this, however, remains to be elucidated. Full article

Isocitrate dehydrogenase 1 (IDH1) mutations are key drivers of glioma biology, influencing tumor aggressiveness and treatment response. To elucidate their molecular impact, we performed proteome analysis on patient-derived (PD) and U87MG glioma cell models with either mutant or wild-type IDH1. We quantified over 6000 protein groups per model, identifying 1594 differentially expressed proteins in PD-AS (IDH1_MUT) vs. PD-GB (IDH1_WT) and 904 in U87_MUT vs. U87_WT. Both IDH1_MUT models exhibited enhanced MHC antigen presentation and interferon signaling, indicative of an altered immune microenvironment. However, metabolic alterations were model-dependent: PD-AS cells shifted toward glycolysis and purine salvage, while U87_MUT cells retained oxidative phosphorylation, potentially due to D2-hydroxyglutarate (2OHG)-mediated HIF1A stabilization. We also observed a predominance of downregulated DNA repair proteins in IDH1_MUT models, particularly those involved in homologous recombination. In contrast, RB1 and ASMTL were strongly upregulated in both IDH1_MUT models, implicating them in DNA repair and cellular stress responses. We also found distinct expression patterns of proteins regulating histone methylation in IDH1_MUT cells, favoring increased methylation of H3K4, H3K9, and H3K36. A key driver of this may be the upregulation of SETD2 in PD-AS, an H3K4 and H3K36 trimethyltransferase linked to the recruitment of HIF1A as well as DNA mismatch repair proteins. This study uncovers candidate biomarkers and pathways relevant to glioma progression and therapeutic targeting, but also underscores the complexity of predicting glioma pathogenesis and treatment responses based on IDH1 mutation status. While proteome profiling provides valuable insights, a comprehensive understanding of IDH1_MUT gliomas will likely require integrative multi-omics approaches, including DNA/RNA methylation profiling, histone and protein post-translational modification analyses, and targeted DNA damage and repair assays. Full article

Asthma is a chronic inflammatory airway disease influenced by both genetic and environmental factors. Recent insights have underscored the pivotal role of epigenetic regulation in the pathogenesis and heterogeneity of asthma. This review focuses on key epigenetically important regulators categorized as writers, erasers, and readers that govern DNA methylation, histone modifications, and RNA modifications. These proteins modulate gene expression without altering the underlying DNA sequence, thereby influencing immune responses, airway remodeling, and disease severity. We highlight the structural and functional dynamics of histone acetyltransferases (e.g., p300/CBP), histone deacetylases (e.g., SIRT family), DNA methyltransferases (DNMT1, DNMT3A), demethylases (TET1), and methyl-CpG-binding proteins (MBD2) in shaping chromatin accessibility and transcriptional activity. Additionally, the m6A RNA modification machinery including METTL3, METTL14, FTO, YTHDF1/2, IGF2BP2, and WTAP is explored for its emerging significance in regulating post-transcriptional gene expression during asthma progression. Structural characterizations of these proteins reveal conserved catalytic domains and interaction motifs, mirroring their respective families such as SIRTs, p300/CBP, DNMT1/3A, and YTHDF1/2 critical to their epigenetic functions, offering mechanistic insight into their roles in airway inflammation and immune modulation. By elucidating these pathways, this review provides a framework for the development of epigenetic biomarkers and targeted therapies. Future directions emphasize phenotype-specific epigenomic profiling and structure-guided drug design to enable precision medicine approaches in asthma management. Full article

Epigenetic regulation, particularly DNA methylation, plays a crucial role in plant adaptation to environmental stresses by modulating gene expression without altering the underlying DNA sequence. In response to major abiotic stresses such as salinity, drought, heat, cold, and heavy metal toxicity, plants undergo dynamic changes in DNA methylation patterns. These modifications are orchestrated by DNA methyltransferases and demethylases with variations depending on plant species, genetic background, and ontogenic phase. DNA methylation affects the expression of key genes involved in cellular, physiological, and metabolic processes essential for stress tolerance. Furthermore, it contributes to the establishment of stress memory, which can be transmitted across generations, thereby enhancing long-term plant resilience. The interaction of DNA methylation with other epigenetic mechanisms, including histone modifications, small RNAs, and chromatin remodeling, adds layers of regulatory complexity. Recent discoveries concerning N6-methyladenine have opened new avenues for understanding the epigenetic landscape in plant responses to abiotic stress. Overall, this review addresses the central role of DNA methylation in regulating plant stress responses and emphasizes its potential for application in crop improvement through epigenetic and advanced biotechnological approaches. Full article

Quaternary ammonium compounds (QACs) are a class of chemicals used for their antimicrobial, surfactant, and antistatic properties. QACs are present in many consumer products, and people are regularly exposed to them. We have previously shown reproductive toxicity in mice exposed to the disinfectants alkyl dimethyl benzyl ammonium chloride (ADBAC) and dodecyl dimethyl ammonium chloride (DDAC). To assess the long-term reproductive impacts, a generational reproductive study was conducted. Sperm parameters were determined by CASA and epigenetic enzyme mRNA expression was determined by pathway-focused RT-PCR. Mice ambiently exposed to ADBAC+DDAC exhibited decreases in reproductive indices that persisted through the F1 generation. Male mice (F0) dosed with 120 mg/kg/day of ADBAC+DDAC exhibited decreased sperm concentration and motility that persisted through the F1 generation. Changes in the mRNA expression of chromatin-modifying enzymes in the testes were seen. Two histone acetyltransferases (Hat1 and Kat2b) were upregulated, and one lysine-specific demethylase (Kdm6b) was downregulated in the F0 generation. The DNA methyltransferase Dnmt1 was downregulated in F1 males. These changes in chromatin-modifying enzymes are known to decrease fertility and could be a mechanism for ADBAC+DDAC reproductive toxicity. In all experiments, the F2 generation was similar to the controls, showing multi-generational but not trans-generational epigenetic inheritance. Full article

DNA methylation, mediated by DNA methyltransferases (DMTs) and demethylases (DMLs), is an important epigenetic modification that maintains genomic stability and regulates gene expression in plant growth, development, and stress responses. However, a comprehensive characterization of these gene families in Populus sect. Turanga remains lacking. In this study, eight PeDMT and two PeDML genes were identified in Populus euphratica, and six PpDMT and three PpDML genes in Populus pruinosa. Phylogenetic analysis revealed that DMTs and DMLs could be classified into four and three subfamilies, respectively. The analysis of cis-acting elements indicated that the promoter regions of both DMTs and DMLs were enriched with elements responsive to growth and development, light, phytohormones, and stress. Collinearity analysis detected three segmentally duplicated gene pairs (PeDMT5/8, PeDML1/2, and PpDML2/3), suggesting potential functional diversification. Transcriptome profiling showed that several PeDMTs and PeDMLs exhibited leaf shape- and developmental stage-specific expression patterns, with PeDML1 highly expressed during early stages and in broad-ovate leaves. Whole-genome bisulfite sequencing revealed corresponding decreases in DNA methylation levels, suggesting that active demethylation may contribute to heteromorphic leaf formation. Overall, this study provides significant insights for exploring the functions and expression regulation of plant DMTs and DMLs and will contribute to future research unraveling the molecular mechanisms of epigenetic regulation in P. euphratica. Full article

Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as HIN-1 and RASSF1A, alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to cancer cell plasticity and facilitates epithelial-to-mesenchymal transition (EMT). Key histone modifiers, including KLF5, EZH2, and the demethylases KDM4/6, regulate osteoclastogenic signaling pathways and the transition between metastatic dormancy and reactivation. Simultaneously, SWI/SNF chromatin remodelers such as BRG1 and BRM reconfigure enhancer–promoter interactions that promote bone tropism. Non-coding RNAs, including miRNAs, lncRNAs, and circRNAs (e.g., miR-34a, NORAD, circIKBKB), circulate via exosomes to modulate the RANKL/OPG axis, thereby conditioning the bone microenvironment and fostering the formation of a pre-metastatic niche. These mechanistic insights have accelerated the development of epigenetic therapies. DNA methyltransferase inhibitors (e.g., decitabine, guadecitabine) have shown promise in attenuating osteoclast differentiation, while histone deacetylase inhibitors display context-dependent effects on tumor progression and bone remodeling. Inhibitors targeting EZH2, BET proteins, and KDM1A are now advancing through early-phase clinical trials, often in combination with bisphosphonates or immune checkpoint inhibitors. Moreover, novel approaches such as CRISPR/dCas9-based epigenome editing and RNA-targeted therapies offer locus-specific reprogramming potential. Together, these advances position epigenetic modulation as a promising axis in precision oncology aimed at interrupting the pathological crosstalk between tumor cells and the bone microenvironment. This review synthesizes current mechanistic understanding, evaluates the therapeutic landscape, and outlines the translational challenges ahead in leveraging epigenetic science to prevent and treat bone metastases. Full article

DNA methylation is a conserved and vital epigenetic modification that plays essential roles in plant growth, development, and responses to environmental stress. Cytosine-5 DNA methyltransferases (C5-MTases) and DNA demethylases (dMTases) are key regulators of DNA methylation dynamics. However, a comprehensive characterization of these gene families in sweet potato has remained elusive. In this study, we systematically identified and analyzed eight C5-MTase and five dMTase genes in the genomes of diploid (Ipomoea trifida, 2n = 2x = 30) and autohexaploid (Ipomoea batatas, 2n = 6x = 90) sweet potato. Phylogenetic, structural, and synteny analyses revealed a high degree of conservation among these genes, suggesting their essential roles during evolution. Promoter analysis uncovered multiple cis-acting elements, particularly those responsive to light and hormones. In addition, we examined the expression profiling of IbC5-MTases and IbdMTases genes during storage root development, revealing that several were highly expressed during the early and rapid expansion stages. These findings suggest that C5-MTases and dMTases may contribute to the regulation of storage root formation in sweet potato through epigenetic mechanisms, offering valuable insights for future functional studies and epigenetic breeding efforts. Full article

MSTN has been used as a candidate gene in the genetics, breeding, and improvement of animal breeds. However, the possible mechanism by which the MSTN gene regulates muscle development through PSMA6 is not well understood. Previous methylome and transcriptome sequencing analyses of gluteal muscle tissues from MSTN+/−Luxi cattle and wild-type Luxi cattle identified that the PSMA6 gene exhibited a negative correlation between methylation levels and transcriptional activity. To investigate whether MSTN expression regulates PSMA6 gene expression, we examined the effects of MSTN on DNA methyltransferases (DNMT1, DNMT2, DNMT3A, and DNMT3B) and DNA demethylases (TET1, TET2, and TET3). Additionally, chromatin immunoprecipitation (ChIP) assays were performed to detect the binding interaction between PSMA6 and TET2. In this paper, we first established an MSTN knockdown cellular model to preliminarily validate its regulatory effect on PSMA6 expression. Subsequently, the developmental impact of PSMA6 on bovine skeletal muscle satellite cells was further investigated through both knockdown and overexpression of the PSMA6 gene. Furthermore, we examined changes in the expression of key components of the AKT/mTOR signaling pathway to elucidate the mechanisms underlying the PSMA6-mediated regulation of satellite cell development. The results demonstrate that myostatin (MSTN) inhibition significantly decreased proteasome 20S subunit alpha-6 (PSMA6) gene expression, while increasing demethylase expression, particularly ten-eleven translocation-2 (TET2), which exhibited the most pronounced changes. During the cell proliferation stage, the markers Paired Box 7 (PAX7) and Ki-67 exhibited no significant changes, whereas the PSMA6 gene was either overexpressed or disrupted. Conversely, PSMA6 overexpression altered the myogenic differentiation markers, causing the differential regulation of myosin heavy chain (MyHC) and myogenin (MyoG) expression, with MyHC upregulation and concurrent MyoG downregulation. PSMA6 gene overexpression led to the downregulation of AKT1 and Rac1, as well as the activation of the AKT/mTOR pathway, including key factors such as mTOR, p-mTOR, RPS6, p-RPS6, and RhoA. PSMA6 interference resulted in the downregulation of p-mTOR and the upregulation of p-RPS6. Gene expression profiling in our study revealed that the myostatin (MSTN) knockout model significantly reduced the transcriptional levels of the proteasome α6 subunit (PSMA6) (p < 0.05), with the regulatory intensity showing a significant negative correlation with MSTN expression. This molecular evidence substantiates a negative regulatory axis between MSTN and PSMA6. Functional experiments demonstrated that PSMA6 overexpression specifically enhanced myotube formation rates in bovine skeletal muscle satellite cells, whereas siRNA-mediated PSMA6 knockdown exhibited no significant effects on cellular proliferation, indicating the functional specificity of this gene in myogenic differentiation. Mechanistic investigations further revealed that PSMA6 activates the canonical AKT/mTOR signaling transduction cascade through the phosphorylation of AKT and its downstream effector mTOR, thereby mediating the expression of myogenic regulatory factors MyoD and myogenin. Collectively, these findings demonstrate that MSTN deficiency alleviates the transcriptional repression of PSMA6, remodels skeletal muscle differentiation-associated signaling networks, and ultimately drives the directional differentiation of satellite cells toward myofiber specification. Full article

Plants continuously adapt to their environments by responding to various intrinsic and extrinsic signals. They face numerous biotic and abiotic stresses such as extreme temperatures, drought, or pathogens, requiring complex regulatory mechanisms to control gene activity and adapt their proteome for survival. Epigenetic regulation plays a crucial role in these adaptations, potentially leading to both heritable and non-heritable changes across generations. This process enables plants to adjust their gene expression profiles and acclimate effectively. It is also vital for plant development and productivity, affecting growth, yield, and seed quality, and enabling plants to “remember” environmental stimuli and adapt accordingly. Key epigenetic mechanisms that play significant roles include DNA methylation, histone modification, and ubiquitin ligase complex activity. These processes, which have been extensively studied in the last two decades, have led to a better understanding of the underlying mechanisms and expanded the potential for improving agriculturally and economically important plant traits. DNA methylation is a fundamental process that regulates gene expression by altering chromatin structure. The addition of methyl groups to cytosines by DNA methylases leads to gene suppression, whereas DNA demethylases reverse this effect. Histone modifications, on the other hand, collectively referred to as the “histone code”, influence chromatin structure and gene activity by promoting either gene transcription or gene silencing. These modifications are either recognized, added, or removed by a variety of enzymes that act practically as an environmental memory, having a significant impact on plant development and the responses of plants to environmental stimuli. Finally, ubiquitin ligase complexes, which tag specific histones or regulatory proteins with ubiquitin, are also crucial in plant epigenetic regulation. These complexes are involved in protein degradation and play important roles in regulating various cellular activities. The intricate interplay between DNA methylation, histone modifications, and ubiquitin ligases adds complexity to our understanding of epigenetic regulation. These mechanisms collectively control gene expression, generating a complex and branching network of interdependent regulatory pathways. A deeper understanding of this complex network that helps plants adapt to environmental changes and stressful conditions will provide valuable insights into the regulatory mechanisms involved. This knowledge could pave the way for new biotechnological approaches and plant breeding strategies aimed at enhancing crop resilience, productivity, and sustainable agriculture. Full article

Background/Objectives: RNA-modifying proteins play a crucial role in the progression of cancer. The fat mass and obesity-associated protein (FTO) and alkB homolog 5 RNA demethylase (ALKBH5) are RNA-demethylating proteins that have contrasting effects in renal cell carcinoma (RCC) among different populations. This research investigates the genotype and expression levels of FTO and ALKBH5 in RCC patients from the Middle East and Northern Africa (MENA) region. Methods: Formalin-fixed paraffin-embedded samples from the kidney biopsies of RCC patients and controls were examined using targeted DNA sequencing, whole transcriptome profiling, and immunohistochemistry. Results: Our findings show that the rs11075995T variant in FTO is associated with a heightened risk of clear-cell RCC (ccRCC). ALKBH5 and FTO protein expression were significantly lower in ccRCC and chromophobe RCC (chRCC) patients but not in papillary RCC (pRCC) patients. In ccRCC, transcriptomic data revealed a significant downregulation of FTO (log₂FC = −5.2, q < 0.001) and ALKBH5 (log₂FC = −4.7, q < 0.001) compared to controls. A significant negative correlation was found in ccRCC between FTO expression and T allele frequency in rs11075995, suggesting that FTO expression is affected. Conclusions: This is the first demonstration of the association of the dysregulated expression of FTO and ALKBH5 in ccRCC and chRCC patients from the MENA region. FTO variant rs11075995T increased the risk of ccRCC and was negatively associated with FTO protein expression. Full article