Search Results (927)

Environmental pollutants such as heavy metals, endocrine-disrupting chemicals, microplastics, and airborne particulates are increasingly recognized for their potential to influence immune function through epigenetic mechanisms. This review examines conserved pollutant-associated pathways at interfaces of immunity and epigenetics, with particular attention to Toll-like receptor–NF-κB signalling, NLRP3 inflammasome activity, and reactive oxygen species-driven cascades. Evidence from cellular, animal, and epidemiological studies indicates that these pathways may converge on chromatin regulators such as DNA methyltransferases, histone deacetylases, and EZH2, leading to DNA methylation shifts, histone modifications, and altered chromatin accessibility. Pollutants are also reported to modulate non-coding RNAs, including miR-21, miR-155, and several lncRNAs, which can act as intermediaries between cytokine signalling and epigenetic remodelling. Findings from transgenerational models suggest that pollutant-linked immune–epigenetic alterations might persist across generations, raising the possibility of long-term consequences for immune and neurodevelopmental health. Comparative analyses further indicate convergence across diverse pollutant classes, pointing to a shared mechanistic axis of immune–epigenetic disruption. Overall, these insights suggest that pollutant-induced immune–epigenetic signatures may contribute to inflammation, altered immune responses, and heritable disease risks, and their clarification could inform biomarker discovery and future precision approaches in immunotoxicology. Full article

As a crucial aspect of epigenetic research, DNA methylation is fundamental to genomic stability, gene transcription regulation, and chromatin remodeling. Rice is a staple food source for roughly half of the world’s population. Therefore, optimizing rice yield and stress tolerance is vital for global food security. With the continuous advancement of DNA methylation detection technologies, studies have shown that DNA methylation regulates various rice growth and development processes, including root differentiation and grain development, through the dynamic equilibrium of de novo methylation, maintenance methylation, and demethylation. Furthermore, DNA methylation is crucial in the plant’s response to environmental stressors like high or low temperature, drought and salinity. The patterns of DNA methylation modifications are also closely linked to rice domestication and heterosis formation. Therefore, a comprehensive investigation of the DNA methylation regulatory network holds significant theoretical value for rice genetic improvement and molecular breeding. This review offers a systematic analysis of the molecular mechanisms and detection technologies of DNA methylation, as well as its regulatory roles in rice growth and development, stress responses, and other biological processes, aiming to provide a theoretical foundation for rice genetic improvement research. 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

Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a complex molecular landscape. Despite extensive research, our understanding of the molecular mechanisms remains incomplete, hindering the development of effective therapeutic strategies for this disease. Long non-coding RNAs (lncRNAs) have emerged as crucial factors in cancer biology, regulating key networks across various malignancies. These molecules exert their regulatory functions through interactions with nucleic acids or proteins, thereby influencing signaling pathways within tumor cells. Consequently, lncRNAs play a significant role in key processes like cell proliferation, metastasis, immune evasion, and treatment resistance. This review offers a comprehensive overview of current knowledge regarding lncRNA-mediated mechanisms in HNSCC. The first section explores how lncRNAs influence tumor processes through various modulation mechanisms, including transcriptional and post-transcriptional regulation, chromatin remodeling, and epigenetic modifications. We also highlight the impact of lncRNAs on specific signaling pathways that control essential cellular functions (e.g., proliferation, apoptosis, angiogenesis, invasion, metastasis). Ultimately, this underscores the promising potential of lncRNAs as diagnostic biomarkers and therapeutic targets capable of enhancing patient care in oncology. Gaining a deep understanding of how lncRNAs modulate carcinogenic mechanisms may yield innovative approaches for early detection, personalized treatment, and improved clinical outcomes for HNSCC patients. Full article

Hepatocellular carcinoma (HCC), the most prevalent primary liver cancer, continues to pose a significant global health burden due to its high mortality rate. In addition to genetic alterations, epigenetic aberrations, including DNA methylation, histone modifications, chromatin remodeling, and noncoding RNA (ncRNA) dysregulation, play critical roles in HCC initiation and progression. Notably, miR-375 and miR-483-5p are among the most dysregulated miRNAs in HCC, with their altered expression levels closely associated with tumor stage and patient survival. These epigenetic modifications offer promising therapeutic avenues due to their reversibility and dynamic nature. Furthermore, specific epigenetic signatures such as CDH1 promoter hypermethylation and HOTAIR overexpression are being explored as potential biomarkers for early detection and treatment response. In this chapter, we review recent advances in the epigenetic landscape of HCC and discuss their diagnostic and therapeutic implications, highlighting their potential to improve patient outcomes through personalized medicine approaches. Full article

Intrinsically disordered regions (IDRs) are present in nearly all proteins, often accounting for more than 40% of their amino acid sequence. Unlike structured domains, IDRs lack sequence or structural conservation across species while maintaining conserved biological functions. Here, we discovered that the previously uncharacterized disordered tail region of Poly(ADP-ribose) glycohydrolase (PARG) controls its localization and activity. Despite its structural divergence, this domain supports conserved regulatory functions across species. Deletion of the disordered tail results in cytoplasmic mislocalization, aberrant accumulation in the nucleolus, impaired chromatin association, and reduced enzymatic activity. Mass spectrometry analysis reveals that this disordered region mediates interactions with nuclear transport factors, post-translational modification enzymes, and chromatin-associated complexes. Together, these results demonstrate that the disordered tail region of PARG acts as a regulatory hub that integrates multiple layers of control to ensure proper subcellular localization and chromatin function. Full article

Nuclear processes are fundamental to the regulation of cellular, tissue, and organismal function, especially in complex multicellular systems. Central to these processes are lamins and lamin-associated proteins, which contribute to nuclear structure, gene expression, and chromatin organization. The discovery that mutations in genes coding for lamins and lamina-associated proteins give rise to rare disorders—collectively called laminopathies—has intensified interest in this field among cell biologists and medical scientists. While many practical and clinically relevant questions about phenotype development and potential treatments require mammalian models, key molecular mechanisms and interactions have also been effectively studied in both vertebrate and invertebrate systems. This review focuses on a discussion of Drosophila lamins, their major properties, functions, interactions and post-translational modifications, with comparison to mammalian lamins, and a discussion of the value of fly models in studies of lamins in muscle tissue development and function in comparison to mammalian lamin B-type and A/C-type. In this paper, we have discussed the overall impact of lamin Dm and lamin C level manipulations on overall phenotype, especially on larval and adult muscles. We have thoroughly discussed the conclusions, which may have been drawn from experiments with overexpression of lamin C mutants mimicking lamin A laminopathy mutations. We have presented and discussed the suggestion that the mechanisms underlying Drosophila muscle phenotype development are similar not only to human dystrophic laminopathies but also to classical human muscular dystrophies such as Duchenne muscular dystrophy and Hutchison–Gilford Progeria syndrome. We suggest that the activation of the stress response contributes to the laminopathic phenotype detected in Drosophila. Finely, this review discusses in depth the lamin Dm and lamin C interactomes, discrepancies between String-based interactome networks, and our map of interactomes based on manual verification of experimental data on Drosophila lamin interactions. Full article

Epigenetic regulation is critical to B cell development, guiding gene expression via DNA methylation, histone modifications, chromatin remodeling, and noncoding RNAs. In mature B cell neoplasms, particularly diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL), these mechanisms are frequently disrupted. Recurrent mutations in key epigenetic regulators such as EZH2, KMT2D, CREBBP, and TET2 lead to altered chromatin states, repression of tumor suppressor genes, and enhanced oncogenic signaling. Dysregulation of specific microRNAs (e.g., miR-155, miR-21) further contributes to pathogenesis and therapeutic resistance. In DLBCL, hypermethylation of SMAD1 and CREBBP mutations are associated with immune evasion and chemoresistance. In FL, EZH2 gain-of-function and KMT2D loss-of-function mutations alter germinal center B cell programming, while in CLL, DNA hypomethylation patterns reflect the cell of origin and correlate with clinical outcome. Targeted therapies such as the EZH2 inhibitor tazemetostat have demonstrated efficacy in EZH2-mutant FL, while HDAC and BET inhibitors show variable responses across B cell malignancies. The limitations of current epigenetic therapies reflect the complexity of targeting epigenetic dysregulation rather than therapeutic futility. These challenges nonetheless highlight the relevance of epigenetic alterations as biomarkers and therapeutic targets, with potential to improve the management of mature B cell neoplasms. Full article

Numerous infants have been conceived by in vitro fertilization (IVF) and other assisted reproductive technologies (ART). Increasing evidence indicates that these approaches induce minor alterations in molecules during the initial phases of embryogenesis. This narrative review examines the molecular pathophysiology of embryonic cardiogenesis in the context of assisted reproductive technology, emphasizing transcriptional and epigenetic regulation. Essential transcription factors for cardiac development, including NKX2-5, GATA4, TBX5, ISL1, MEF2C, and HAND1/2, play a crucial role in mesodermal specification, heart tube formation, and chamber morphogenesis. Animal models and human preimplantation embryos have demonstrated that ART-related procedures, including gamete micromanipulation, supraphysiological hormone exposure, and extended in vitro culture, can alter the expression or epigenetic programming of these genes. Subsequent to ART, researchers have identified anomalous patterns of DNA methylation, alterations in histones, and modifications in chromatin accessibility in cardiogenic loci. These alterations indicate that errors occurred during the initial reprogramming process, potentially resulting in structural congenital heart abnormalities (CHDs) or modifications in cardiac function later in life. Analysis of the placental epigenome in babies conceived using assisted reproductive technology reveals that imprinted and developmental genes critical for cardiac development remain dysfunctional. This review proposes a mechanistic theory about the potential subtle alterations in the cardiogenic gene network induced by ART, synthesizing findings from molecular embryology, transcriptomics, and epigenomics. Understanding these molecular issues is crucial not only for enhancing ART protocols but also for evaluating the cardiovascular risk of children conceived by ART postnatally and for early intervention. Full article

Obesity represents a global medical and social challenge characterized by pathological accumulation of adipose tissue as a result of complex interactions among genetic, environmental, and epigenetic factors. Recent studies have highlighted the pivotal role of epigenetic mechanisms in the pathogenesis of this condition, including abnormal DNA methylation of metabolic genes, dysregulation of microRNAs, and chromatin remodeling. These modifications are reversible and can be modulated by dietary, behavioral, and pharmacological interventions. This review provides a comprehensive analysis of tissue-specific epigenetic alterations identified not only in adipocytes and hepatocytes but also in peripheral blood cells, offering promising opportunities for the development of novel diagnostic biomarkers and targeted epigenetic therapeutic strategies. Full article

Female gametogenesis is orchestrated by dynamic epigenetic modifications. In mammals, SETDB1, a histone H3K9 methyltransferase, is required for proper meiotic progression and early embryonic development. In Drosophila, the ortholog of SETDB1 plays a critical role in germ cell differentiation, transposon silencing, and the transcriptional repression of specific germline genes during oocyte fate determination. Moreover, Polycomb group (PcG) proteins in both mammals and Drosophila are essential for primary oocyte viability and meiosis, functioning through the silencing of early prophase I genes during later stages of prophase. While the repressive roles of epigenetic regulators in both Drosophila and mammalian oogenesis are well characterized, the functions of epigenetic activators remain less defined. Gene expression is controlled by the opposing activities of PcG and Trithorax group (TrxG) proteins, with the latter constituting a diverse family of chromatin remodelling factors that include H3K4 methyltransferases. In Drosophila, SET domain containing 1 (Set1)—the ortholog of mammalian SETD1A/B—acts as the primary regulator of global H3K4me2/3 levels. Set1 is critical for germline stem cell (GSC) self-renewal, functioning through both cell-autonomous and non-cell-autonomous mechanisms, with its depletion in the germline resulting in a progressive loss of GSC. More recently, Set1 has been implicated in germline cyst differentiation, although the mechanisms underlying this role remain poorly understood due to the complexity of the observed phenotypes. To investigate this, we analyzed ovaries from recently eclosed females in which Set1 and its highly conserved COMPASS partner, absent, small, or homeotic discs 2 (Ash2), were depleted—thus minimizing the confounding effects from GSC loss. We observed striking defects in both oocyte determination and Synaptonemal Complex (SC) integrity in one- to two-day-old females, within otherwise normal egg chambers. Interestingly, while defects in oocyte fate and oocyte–chromatin architecture were partially recovered in older egg chambers, SC integrity remained compromised. These findings suggest a critical window for SC assembly during germline cyst differentiation, after which this assembly cannot occur. Full article

Neurocutaneous syndromes, known as phakomatoses, encompass a diverse group of congenital conditions affecting the nervous system and skin, with neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) among the most clinically significant. Both disorders are inherited in an autosomal dominant manner. NF1 presents with café-au-lait macules; cutaneous, subcutaneous, and plexiform neurofibromas; skeletal abnormalities; learning disabilities; and optic pathway gliomas, while NF2 is characterised by bilateral vestibular schwannomas, multiple meningiomas, ependymomas, and peripheral nerve schwannomas. Although germline mutations in the NF1 and NF2 tumour suppressor genes are well established, they do not fully explain the broad clinical variability observed, even among individuals carrying identical mutations. As increasingly recognised in other genetic diseases, epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodelling, and non-coding RNA (ncRNA) regulation, play a critical role in modulating gene expression and influencing disease severity. Despite important findings, the research remains fragmented, and a unified model is lacking. This review organises the current knowledge, emphasising how epigenetic alterations impact disease behaviour and outlining their potential as prognostic biomarkers and therapeutic targets. A deeper understanding of these mechanisms could lead to improved personalised management and the development of targeted epigenetic therapies for individuals with NF1 and NF2. Full article

Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression and cellular signaling in cancer. Their functions are primarily mediated through interactions with specific protein partners that modulate chromatin structure, epigenetic remodeling, transcription, and signal transduction. In this review, we explore reports and strategies for the proteomic characterization of lncRNA-associated proteins, particularly emphasizing high-throughput liquid chromatography–mass spectrometry (LC-MS)-based techniques. Affinity-based methods such as RNA pull-down, ChIRP MS, RAP-MS, BioID-MS, and SILAC-MS enable sensitive and specific mapping of lncRNA and protein complexes. These approaches reveal cancer-specific proteomic signatures, post-translational modifications, and mechanistic insights into tumor biology. The use of label-free quantification, bituminization, and crosslinking strategies further enhances the resolution of dynamic RNA–protein networks. Validation tools following bioinformatic analyses, such as Western blotting, immunohistochemistry, immunofluorescence, and ELISA, are used to prioritize and confirm findings. Candidate biomarkers from hepatocellular carcinoma to colorectal and prostate cancers, profiling lncRNA-associated proteins, hold promise for identifying clinically actionable biomarkers and therapeutic targets. This review highlights the translational relevance of lncRNA protein studies and advocates for their broader adoption in oncological research. In LC-MS workflows, proteins bound to lncRNAs are enzymatically digested into peptides, separated via nano-LC, and analyzed using high-resolution tandem MS. Label-free or isotope-labeled methods quantify differential enrichment, followed by bioinformatics-driven pathway annotation. Full article

The impact of ionizing radiation (IR) with induction of various DNA damage is based not only on genetic but also on epigenetic effects. Epigenetic modifications determine the chromatin structure and DNA accessibility, thereby regulating cellular functions through the expression of individual genes or entire groups of genes. However, the influence of DNA repair processes on the restoration of local chromatin structures and global nuclear architectures is still insufficiently understood. In multicellular organisms, epigenetic mechanisms control diverse cellular functions of specific cell types through precise temporal and spatial regulation of gene expression and silencing. How altered epigenetic mechanisms regulate the pathophysiological function of cells, tissues, and ultimately entire organs following IR exposure remains to be investigated in detail. Radiation-induced epigenetic processes are particularly critical for immature cell populations such as tissue-specific stem and progenitor cells during development and differentiation of organ tissues. Genome-wide patterns of DNA and histone modifications are established cell types—specifically during the development and differentiation of organ tissues but can also be fundamentally altered in adult organism by stress responses, such as radiation-induced DNA damage. Following IR exposure, epigenetic factors are not always fully restored to their original state, resulting in epigenetic dysfunction that causes cells to lose their original identity and function. Moreover, severe radiation-induced DNA damage can induce premature senescence of cells in complex tissues, which ultimately leads to signs of aging and age-related diseases such as cancer. In this work, we provide an overview of the most important epigenetic changes following IR exposure and their pathophysiological significance for the development of acute and chronic radiation reactions. Full article