Epigenetic regulation in tooth development

Changes in the epigenome induced by the environment have been documented in diverse animal phyla, ranging from insects to rodents to humans.These include chromatin remodeling, histone tail modifi cations, and DNA methylation, and more recently the list has expanded to encompass noncoding RNA and microRNA gene regulation (Matzke and Birchler 2005).Thus, it is increasingly recognized that exposure to chemical, nutritional, behavioral, and physical factors alters gene expression and affects health and disease not only through mutation of but also through modifi cation of the epigenome.Moreover, such exposures have been directly linked with subsequent disease formation through deregulation of epigenetic mechanisms.Unlike genetic mutations, these epigenetic changes are potentially reversible, providing a unique avenue to improve human health.Consequently research in epigenetics has increased dramatically in the last few years (Figure 1).The term "epigenetics" was popularized in the early 1940s by developmental biologist Conrad Waddington (1940) to explain "the interactions of genes with their environment, which bring the phenotype into being."In the 1970s, Holliday and Pugh (1975) fi rst proposed covalent chemical DNA modifi cations, including methylation of cytosine-guanine (CpG) dinucleotides, as the molecular mechanism to explain Waddington's hypothesis.The revelations several decades later that X inactivation in mammals and genomic imprinting are regulated by complex and multifactorial mechanisms (Monk 1988;Willard et al. 1993) resulted in an updated definition, describing epigenetics as heritable changes in gene expression that occur without a change in DNA sequence, including the modifi cation of DNA methylation and chromatin remodeling (Wolfe and Matzke 1999).The genomics revolution inspired the investigation of genome-wide rather than local gene analyses, and the term "epigenomics" was

Genes, epigenetic regulation and environmental factors: Which is the most relevant in developing autoimmune diseases?

Epigenetic regulation of cellular identity and function is at least partly achieved through changes in covalent modifications on DNA and histones. Much progress has been made in recent years to understand how these covalent modifications affect cell identity and function. Despite the advances, whether and how epigenetic factors contribute to memory formation is still poorly understood. In this review, we discuss recent progress in elucidating epigenetic mechanisms of learning and memory, primarily at the DNA level, and look ahead to discuss their potential implications in reward memory and development of drug addiction.

Background: Substance use disorder (SUD) is closely associated with epigenetic modifications that significantly impact mental health outcomes. Alcohol and drug misuse induce widespread changes in the epigenome and transcriptome of the central nervous system, disrupting critical processes such as reward signaling and emotional regulation. These alterations in epigenetic regulation and gene expression often persist even after substance cessation, potentially contributing to the onset or worsening of psychiatric conditions, including schizophrenia, depression, stress, and anxiety. Summary: This review delves into key epigenetic mechanisms underlying SUD and its comorbid psychiatric disorders, with a focus on DNA methylation, histone modifications, and noncoding RNA regulation. Additionally, it examines the influence of environmental and biological factors on the epigenome and evaluates emerging epigenetic-based therapeutic strategies aimed at treating SUD and related psychiatric conditions. Key Messages: Gaining a deeper understanding of the epigenetic mechanisms driving SUD and its associated psychiatric disorders is crucial for the development of effective therapeutic interventions. This review highlights the potential of epigenetic-based pharmacological strategies to mitigate the societal and personal burdens linked to SUD and its mental health complications.

Update on epigenetics in allergic disease

Regulatory T cells (Tregs) are central mediators of immune tolerance, yet within tumors they adopt specialized phenotypes that confer the potent suppression of anti-tumor immune responses. Emerging evidence indicates that this functional plasticity is not driven by genetic alterations but instead arises from dynamic and context-dependent epigenetic reprogramming. While individual epigenetic mechanisms controlling Treg development and stability have been described, how tumor-derived cues reshape Treg epigenetic states, how these programs differ across cancer types, and which features distinguish tumor-infiltrating Tregs from their peripheral counterparts remain incompletely understood. In this review, we synthesize recent advances in DNA methylation, histone modifications, chromatin accessibility, and non-coding RNA regulation that govern Treg identity and function with a particular emphasis on tumor-specific epigenetic adaptations. We highlight emerging epigenetic hallmarks of intratumoral Tregs, discuss unresolved mechanistic questions, and evaluate the therapeutic potential and limitations of targeting epigenetic pathways to selectively modulate Tregs in cancer. By integrating mechanistic, cancer-specific, and translational perspectives, this review aims to provide a conceptual framework for understanding how epigenetic regulation shapes Treg behavior in the tumor microenvironment and how it may be exploited for cancer immunotherapy.

Epigenetic regulation of transcription refers to reversible, heritable changes in gene expression that occur in the absence of changes in DNA sequence. A major epigenetic mechanism involves the covalent modification of nucleosomal histones to create binding sites for transcriptional regulators and chromatin remodeling complexes that mediate activation or repression of transcription. While it has been known for a number of years that many histone modifications are reversible, it has only recently been shown that methyl groups are enzymatically removed from lysine residues. Here we discuss the recent characterization of a new class of demethylase enzyme, the JARID1 family, that catalyzes the removal of methyl groups from lysine 4 of histone H3. We summarize recent findings regarding the function of this family of proteins, focusing on our characterization of Little imaginal discs (Lid), the sole JARID1 family protein in Drosophila, which is rate-limiting for Myc-induced cell growth. Finally, we propose models to explain the role of Lid in Myc-mediated growth and discuss the relevance of these findings to human disease and tumor formation.

Epigenetics is defined as an inheritable effect that influences gene activity, but does not involve a change in DNA sequence. Epigenetic gene regulation has an essential role in determining individual gene function and activity in each specific cell type. Epigenetics includes four predominant mechanisms: DNA methylation, histone modification, nucleosome positioning and microRNA (miRNA). These mechanisms influence gene expression, cell differentiation, proliferation, DNA repair and replication. Epigenetic modifications are far more sensitive to environmental stimuli than DNA sequence alterations. Candidate gene approaches have identified a small set of genes that undergo epigenetic changes, such as aberrant DNA demethylation, histone modification, as well as regulation by miRNA in rheumatic diseases. It is well known that T cells from patients with SLE or RA, as well as synovial fibroblasts from individuals with RA, have sequences undergoing DNA hypomethylation and/or histone modifications. In addition, miRNA regulates the gene expression by pairing with its target mRNAs and is often deregulated in systemic rheumatic diseases. High-throughput approaches are necessary for screening the epigenetic alterations, and it is essential to screen the specific tissue and cell types that are relevant to the disease pathogenesis. Identification of cell-specific targets of the epigenetic deregulation in rheumatic disorders will provide clinical markers for the diagnosis, disease progression and response to therapy. Our understanding of epigenetics is in its infancy. New generation of pharmaceuticals, which manipulate the epigenome to the switch targeted genes on or off are under investigation. The new field of repairing or optimizing the epigenome through epigenetic modifier and/or diet is wide open.

Introduction Oral squamous cell carcinoma (OSCC) is a heterogeneous malignancy with rapid progression, limited therapeutic options, and poor prognosis. Epigenetic alterations – including DNA methylation, histone modifications, and noncoding RNA (ncRNA) regulation – are key drivers of oncogene activation and tumor suppressor silencing, offering novel therapeutic opportunities. Areas covered This review summarizes the major epigenetic mechanisms in OSCC and highlights recent progress in therapeutic agents and molecular targets. In particular, we emphasize ncRNA-based modulators, such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), which play crucial roles in epigenetic regulation and represent promising therapeutic candidates. Innovative delivery strategies, including exosome-mediated transfer and nanoparticle formulations, are discussed for their potential to improve treatment specificity and overcome resistance. An updated summary of clinical trials targeting epigenetic regulators in OSCC is also presented, along with possible combination strategies to enhance clinical outcomes. Expert commentary Epigenetic therapies hold significant promise for precision treatment of OSCC. Combining targeted agents with advanced delivery systems may accelerate clinical translation, while validated biomarkers could support early detection, risk stratification, and personalized therapy. A literature search was conducted in PubMed and ClinicalTrials.gov from January 2002 to July 2025 to identify high-quality studies on epigenetic therapies in OSCC.

Ovarian cancer (OC) is one of the most lethal gynecologic malignancies globally. In spite of positive responses to initial therapy, the overall survival rates of OC patients remain poor due to the development of drug resistance and consequent cancer recurrence. Indeed, intensive studies have been conducted to unravel the molecular mechanisms underlying OC therapeutic resistance. Besides, emerging evidence suggests a crucial role for epigenetic modifications, namely, DNA methylation, histone modifications, and non-coding RNA regulation, in the drug resistance of OC. These epigenetic modifications contribute to chemoresistance through various mechanisms, namely, upregulating the expression of multidrug resistance proteins (MRPs), remodeling of the tumor microenvironment, and deregulated immune response. Therefore, an in-depth understanding of the role of epigenetic mechanisms in clinical therapeutic resistance may improve the outcome of OC patients. In this review, we will discuss the epigenetic regulation of OC drug resistance and propose the potential clinical implications of epigenetic therapies to prevent or reverse OC drug resistance, which may inspire novel treatment options by targeting resistance mechanisms for drug-resistant OC patients.

Nutrigenomics explore how foods and bioactive compounds interact with our genes and epigenome to influence overall health, while food safety examines how dietary hazards can disrupt these pathways. Integrating both fields aids in the prevention and management of chronic non-communicable diseases (NCDs). Nutrients such as polyphenols, omega-3 fatty acids and methyl donors can modulate key epigenetic mechanisms, including DNA methylation, histone modifications and non-coding RNA regulation, helping protect against metabolic disorders and some types of cancer. Conversely, exposure to harmful substances, including mycotoxins, heavy metals, endocrine-disrupting chemicals and food processing by-products, can trigger oxidative stress, disturb the gut microbiome and alter epigenetic regulation, increasing disease risk. This narrative, non-systematic review synthesizes evidence published between 2000 and 2025, emphasizing the surge in studies since 2020. Relevant articles were retrieved from PubMed, Scopus, Web of Science and Google Scholar using combinations of keywords related to nutrigenomics, epigenetics, food safety, and chronic diseases. In total, 235 publications were analyzed, highlighting nutrigenomics and food safety as an emerging scientific hotspot. Recent advances in multi-omics and microbiome research have enabled precision nutrition approaches and more accurate risk assessment models for NCDs. Despite challenges such as inconsistent methodologies and limited longitudinal data, integrating nutrigenomics with food safety offers a promising approach for improving metabolic health, achieving sustainable weight management, and reducing the global burden of chronic disease. Priorities include large-scale clinical trials, standardized omics pipelines and validated biomarkers to ensure accessibility to and translational impact in public health.

Globally, arboviral infections are major public health threats, and diseases caused by arboviruses-mainly Zika virus, Dengue virus, West Nile virus, and Japanese encephalitis virus-affect many people. Arboviruses can induce severe neurological disorders through complex interactions with host cellular and immune pathways. Recent global surges in infections highlight the urgent need to understand their neuropathogenic mechanisms. Increasing evidence shows that arboviruses exploit host epigenetic machinery, including DNA methylation, histone modification, and non-coding RNA regulation, to subvert antiviral defenses, modulate immune responses, and promote viral infection within the central nervous system. Here, we summarise current findings on the epigenetic regulation of arboviral infections and their contribution to neuropathology. We also discuss how the reversibility of epigenetic modifications presents novel therapeutic opportunities, with inhibitors targeting histone deacetylases, methyltransferases, and DNA methyltransferases emerging as potential antiviral interventions. Advances in epigenomic profiling offer unprecedented opportunities to dissect virus-host interactions, providing a foundation for precision therapies aimed at mitigating arboviral neuroinvasion and its long-term neurological consequences.

Aging is a complex biological process driven by the dynamic interplay among genetic, environmental, and lifestyle factors. Advances in epigenetics have significantly deepened our understanding of the molecular mechanisms underlying aging, underscoring the critical roles of reversible modifications such as DNA methylation, histone modifications, and noncoding RNA regulation. Emerging evidence suggests that exercise is a potent modulator of these epigenetic processes, capable of reshaping the epigenetic landscape to restore cellular homeostasis, modulate gene expression, and enhance physiological resilience. This review systematically synthesizes current knowledge on how exercise modulates epigenetic mechanisms implicated in aging and delineates the distinct epigenetic adaptations induced by variations in exercise modality, intensity, and duration. By integrating these molecular insights, this review provides a comprehensive mechanistic framework linking exercise-induced epigenetic remodeling to healthy aging, and underscores exercise as a promising intervention to counteract aging-related functional decline and disease progression.

The term epigenetics was first used to refer to the complex interactions between the genome and the environment that are involved in development and differentiation in higher organisms. Today, this term is used to refer to heritable alterations that are not due to changes in DNA sequence. Rather, epigenetic modifications, or tags, such as DNA methylation and histone modification, alter DNA accessibility and chromatin structure, thereby regulating patterns of gene expression. These processes are crucial to normal development and differentiation of distinct cell lineages in the adult organism. They can be modified by exogenous influences, and as such, they can contribute to or be the result of environmental alterations of phenotype or pathophenotype. Importantly, epigenetic programming has a crucial role in the regulation of pluripotency genes, which become inactivated during differentiation. Here, we review the major mechanisms in epigenetic regulation; highlight the role of stable, long-term epigenetic modifications that involve DNA methylation; and discuss those modifications that are more flexible (short-term) and involve histone modifications, such as methylation and acetylation. We will also discuss the role of nutritional and environmental challenges in generational inheritance and epigenetic modifications, concentrating on examples that relate to complex cardiovascular diseases, and specifically dissect the mechanisms by which homocysteine modifies epigenetic tags. Lastly, we will discuss the possibilities of modifying therapeutically acquired epigenetic tags, summarizing currently available agents and speculating on future directions. Chromatin is the complex of chromosomal DNA associated with proteins in the nucleus (for review, see Campos and Reinberg1). DNA in chromatin is packaged around histone proteins, in units referred to as nucleosomes. A nucleosome has 147 base pairs of DNA associated with an octomeric core of histone proteins, which consists of 2 H3-H4 histone dimers surrounded by 2 H2A-H2B dimers. N-terminal histone tails protrude from nucleosomes into the nuclear lumen. …

Metastatic dissemination of epithelial ovarian cancer (EOC) predominantly occurs through direct cell shedding from the primary tumor into the intra-abdominal cavity that is filled with malignant ascitic effusions. Facilitated by the fluid flow, cells distribute throughout the cavity, broadly seed and invade through peritoneal lining, and resume secondary tumor growth in abdominal and pelvic organs. At all steps of this unique metastatic process, cancer cells exist within a multidimensional tumor microenvironment consisting of intraperitoneally residing cancer-reprogramed fibroblasts, adipose, immune, mesenchymal stem, mesothelial, and vascular cells that exert miscellaneous bioactive molecules into malignant ascites and contribute to EOC progression and metastasis via distinct molecular mechanisms and epigenetic dysregulation. This review outlines basic epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA regulators, and summarizes current knowledge on reciprocal interactions between each participant of the EOC cellular milieu and tumor cells in the context of aberrant epigenetic crosstalk. Promising research directions and potential therapeutic strategies that may encompass epigenetic tailoring as a component of complex EOC treatment are discussed.