DNA Histone Research Articles

Role of epigenetics in mangroves: Recent progress and future perspectives.

Epigenetic modifications in plants involve heritable changes in gene expression patterns that are not due to changes in gene sequences. Unlike genetic adaptations, which are long-term evolutionary changes, epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNAs, act as adaptive responses and allow plants to better cope with environmental stresses. As mangroves are uniquely located between the land and sea and remain continuously exposed to varying salinity, submergence, and hypoxia stresses, it is expected that certain epigenetic mechanisms might help them withstand the impacts of recurring stress fluctuations. Therefore, understanding the role of epigenetic regulation in mangrove stress adaptations to the intertidal environment is crucial. Despite only few studies to date having investigated epigenetic responses in mangroves, they nonetheless provide important insights into this process on which to base future research. Here, we present an update on recent progress in mangrove epigenetic research and offer perspectives on the potential roles of various epigenetic players in mangrove adaptations to the intertidal environment.

Cellular Epigenetic Targets and Epidrugs in Breast Cancer Therapy: Mechanisms, Challenges, and Future Perspectives

Breast cancer is the most common malignancy affecting women, manifesting as a heterogeneous disease with diverse molecular characteristics and clinical presentations. Recent studies have elucidated the role of epigenetic modifications in the pathogenesis of breast cancer, including drug resistance and efflux characteristics, offering potential new diagnostic and prognostic markers, treatment efficacy predictors, and therapeutic agents. Key modifications include DNA cytosine methylation and the covalent modification of histone proteins. Unlike genetic mutations, reprogramming the epigenetic landscape of the cancer epigenome is a promising targeted therapy for the treatment and reversal of drug resistance. Epidrugs, which target DNA methylation and histone modifications, can provide novel options for the treatment of breast cancer by reversing the acquired resistance to treatment. Currently, the most promising approach involves combination therapies consisting of epidrugs with immune checkpoint inhibitors. This review examines the aberrant epigenetic regulation of breast cancer initiation and progression, focusing on modifications related to estrogen signaling, drug resistance, cancer progression, and the epithelial–mesenchymal transition (EMT). It examines existing epigenetic drugs for treating breast cancer, including agents that modify DNA, inhibitors of histone acetyltransferases, histone deacetylases, histone methyltransferases, and histone demethyltransferases. It also delves into ongoing studies on combining epidrugs with other therapies and addresses the upcoming obstacles in this field.

The Role of Epigenetic Mechanisms in the Development of PM2.5-Induced Cognitive Impairment

PM2.5 is fine particulate matter with a diameter of less than 2.5 μm. Recent evidence has shown that exposure to PM2.5 markedly elevates the risk of neurodegenerative diseases, neurodevelopmental disorders, and cardiovascular diseases, which may culminate in cognitive impairment. Nevertheless, the precise mechanisms through which PM2.5 affects cognitive function are unclear. Recent studies have demonstrated that PM2.5-induced epigenetic alterations are associated with the development of cognitive impairment. Epigenetic alterations include modifications to DNA methylation, histone modifications, and non-coding RNAs. The underlying mechanisms of epigenetic alterations are related to inflammation, synaptic dysfunction, cardiovascular factors, and alterations in neuronal structure and function. This review reports the latest findings on the relationship between PM2.5-induced epigenetic alterations and the development of cognitive disorders, offering novel insights into the cognitive effects of air pollution.

Harnessing Epigenetics: Innovative Approaches in Diagnosing and Combating Viral Acute Respiratory Infections

Abstract: Acute respiratory infections (ARIs) caused by viruses such as SARS-CoV-2, influenza viruses, and respiratory syncytial virus (RSV), pose significant global health challenges, particularly for the elderly and immunocompromised individuals. Substantial evidence indicates that acute viral infections can manipulate the host’s epigenome through mechanisms like DNA methylation and histone modifications as part of the immune response. These epigenetic alterations can persist beyond the acute phase, influencing long-term immunity and susceptibility to subsequent infections. Post-infection modulation of the host epigenome may help distinguish infected from uninfected individuals and predict disease severity. Understanding these interactions is crucial for developing effective treatments and preventive strategies for viral ARIs. This review highlights the critical role of epigenetic modifications following viral ARIs in regulating the host’s innate immune defense mechanisms. We discuss the implications of these modifications for diagnosing, preventing, and treating viral infections, contributing to the advancement of precision medicine. Recent studies have identified specific epigenetic changes, such as hypermethylation of interferon-stimulated genes in severe COVID-19 cases, which could serve as biomarkers for early detection and disease progression. Additionally, epigenetic therapies, including inhibitors of DNA methyltransferases and histone deacetylases, show promise in modulating the immune response and improving patient outcomes. Overall, this review provides valuable insights into the epigenetic landscape of viral ARIs, extending beyond traditional genetic perspectives. These insights are essential for advancing diagnostic techniques and developing innovative treatments to address the growing threat of emerging viruses causing ARIs globally.

Nuclear morphology, chromatin compaction, and epigenetic changes in lymphocytes of dogs infected with Ehrlichia canis.

Canine monocytic ehrlichiosis (CME), induced by Ehrlichia canis, is an important infectious disease in dogs, characterized by various clinical signs and consequent immune dysfunction. This study aimed to characterize nuclear morphology, chromatin compaction, histone H3 acetylation, and DNA methylation in lymphocytes from dogs naturally infected with E. canis, compared with healthy controls. A total of 30 dogs were included in this study, comprising 15 healthy dogs and 15 dogs with confirmed E. canis infection, verified through polymerase chain reaction. Blood samples were collected from these dogs to isolate peripheral blood mononuclear cells. The isolated cells were prepared into smears and stained using the Feulgen reaction for subsequent analysis. These stained smears underwent video imaging analysis to assess nuclear morphology and chromatin parameters. Additionally, lymphocytes isolated from the PBMCs were analyzed to quantify global levels of histone H3 acetylation and DNA methylation. The results indicated significant increases in nuclear size and alterations in chromatin architecture in the lymphocytes of dogs with E. canis infection. A significant reduction in histone H3 acetylation was observed in this group, suggesting a potential mechanism of transcriptional repression. In contrast, no significant differences in DNA methylation were detected between the infected dogs and the healthy controls. In conclusion, our findings reveal distinct morphological and epigenetic alterations in lymphocytes associated with E. canis infection, thereby enhancing the understanding of the immune dysfunction observed in dogs with CME.

Epigenetic regulation of macrophage function in kidney disease: New perspective on the interaction between epigenetics and immune modulation.

The interaction between renal intrinsic cells and macrophages plays a crucial role in the onset and progression of kidney diseases. In recent years, epigenetic mechanisms such as DNA methylation, histone modification, and non-coding RNA regulation have become essential windows for understanding these processes. This review focuses on how renal intrinsic cells (including tubular epithelial cells, podocytes, and endothelial cells), renal cancer cells, and mesenchymal stem cells influence the function and polarization status of macrophages through their own epigenetic alterations, and how the epigenetic regulation of macrophages themselves responds to kidney damage, thus participating in renal inflammation, fibrosis, and repair. Moreover, therapeutic studies targeting these epigenetic interaction mechanisms have found that the application of histone deacetylase inhibitors, histone methyltransferase inhibitors, various nanomaterials, and locked nucleic acids against non-coding RNA have positive effects on the treatment of multiple kidney diseases. This review summarizes the latest research advancements in these epigenetic regulatory mechanisms and therapies, providing a theoretical foundation for further elucidating the pathogenesis of kidney diseases and the development of novel therapeutic strategies.

Beyond the mono-nucleosome.

Nucleosomes, the building block of chromatin, are responsible for regulating access to the DNA sequence. This control is critical for essential cellular processes, including transcription and DNA replication and repair. Studying chromatin can be challenging both in vitro and in vivo, leading many to use a mono-nucleosome system to answer fundamental questions relating to chromatin regulators and binding partners. However, the mono-nucleosome fails to capture essential features of the chromatin structure, such as higher-order chromatin folding, local nucleosome-nucleosome interactions, and linker DNA trajectory and flexibility. We briefly review significant discoveries enabled by the mono-nucleosome and emphasize the need to go beyond this model system in vitro. Di-, tri-, and tetra-nucleosome arrays can answer important questions about chromatin folding, function, and dynamics. These multi-nucleosome arrays have highlighted the effects of varying linker DNA lengths, binding partners, and histone post-translational modifications in a more chromatin-like environment. We identify various chromatin regulatory mechanisms yet to be explored with multi-nucleosome arrays. Combined with in-solution biophysical techniques, studies of minimal multi-nucleosome chromatin models are feasible.

Epigenetic state and gene expression remain stable after CRISPR/Cas-mediated chromosomal inversions.

The epigenetic state of chromatin, gene activity and chromosomal positions are interrelated in plants. In Arabidopsis thaliana, chromosome arms are DNA-hypomethylated and enriched with the euchromatin-specific histone mark H3K4me3, while pericentromeric regions are DNA-hypermethylated and enriched with the heterochromatin-specific mark H3K9me2. We aimed to investigate how the chromosomal location affects epigenetic stability and gene expression by chromosome engineering. Two chromosomal inversions of different sizes were induced using CRISPR/Cas9 to move heterochromatic, pericentric sequences into euchromatic regions. The epigenetic status of these lines was investigated using whole-genome bisulfite sequencing and chromatin immunoprecipitation. Gene expression changes following the induction of the chromosomal inversions were studied via transcriptome analysis. Both inversions had a minimal impact on the global distribution of histone marks and DNA methylation patterns, although minor epigenetic changes were observed across the genome. Notably, the inverted chromosomal regions and their borders retained their original epigenetic profiles. Gene expression analysis showed that only 0.5-1% of genes were differentially expressed genome-wide following the induction of the inversions. CRISPR/Cas-induced chromosomal inversions minimally affect epigenetic landscape and gene expression, preserving their profiles in subsequent generations.

Exploring the link between genetic disorders and early-onset periodontal disease

Periodontal disease is a complex, multifactorial condition characterized by chronic inflammation and progressive destruction of the tooth-supporting structures. Among its various forms, early-onset periodontitis is particularly aggressive and often associated with genetic predispositions. Genetic and epigenetic factors play pivotal roles in shaping host susceptibility to this disease by influencing immune responses, inflammatory regulation, and tissue homeostasis. Single-nucleotide polymorphisms (SNPs) in genes encoding cytokines, such as interleukin-1β and tumor necrosis factor-alpha, are linked to heightened inflammatory responses, amplifying tissue damage and accelerating disease progression. Additionally, polymorphisms in genes like TLR2 and TLR4 impair microbial recognition, promoting chronic inflammation and dysbiosis. Epigenetic modifications, including DNA methylation and histone acetylation, further modulate gene expression, contributing to the dynamic interplay between genetic predispositions and environmental factors like smoking or poor oral hygiene. Emerging research has also highlighted genetic markers such as human leukocyte antigen (HLA) alleles and matrix metalloproteinase (MMP) variants as predictors of disease severity and therapeutic outcomes. These insights have driven the development of targeted therapies, including inhibitors of pro-inflammatory mediators, MMP inhibitors, and potential miRNA-based interventions. High-throughput technologies, such as genome-wide association studies (GWAS), have expanded the understanding of genetic pathways involved in periodontal disease. These advances enable earlier disease detection and personalized treatment strategies, offering the potential to mitigate progression and reduce the burden of severe periodontitis. The integration of genetic and epigenetic research into clinical practice marks a significant step toward precision medicine, providing a framework for tailored prevention and therapeutic interventions aimed at improving patient outcomes. Future research must continue to explore these genetic mechanisms to uncover novel biomarkers and refine targeted treatment approaches for periodontal disease.

Histone Modifications and DNA Methylation in Psoriasis: A Cellular Perspective.

In recent years, epigenetic modifications have attracted significant attention due to their unique regulatory mechanisms and profound biological implications. Acting as a bridge between environmental stimuli and changes in gene activity, they reshape gene expression patterns, providing organisms with regulatory mechanisms to respond to environmental changes. A growing body of evidence indicates that epigenetic regulation plays a crucial role in the pathogenesis and progression of psoriasis. A deeper understanding of these epigenetic mechanisms not only helps unveil the molecular mechanisms underlying the initiation and progression of psoriasis but may also provide new insights into diagnostic and therapeutic strategies. Given the unique roles and significant contributions of various cell types involved in the process of psoriasis, a thorough analysis of specific epigenetic patterns in different cell types becomes a key entry point for elucidating the mechanisms of disease development. Although epigenetic modifications encompass multiple complex layers, this review will focus on histone modifications and DNA methylation, describinghow they function in different cell types and subsequently impact the pathophysiological processes of psoriasis. Finally, we will summarize the current problems in research concerning histone modifications and DNA methylation in psoriasis and discussthe clinical application prospects and challenges of targeting epigenetic modifications as therapeutic strategies for psoriasis.

A complex interplay between histone variants and DNA methylation.

Nucleosomes, the chromatin building blocks, play an important role in controlling DNA and chromatin accessibility. Nucleosome remodeling and the incorporation of distinct histone variants confer unique structural and biochemical properties, influencing the targeting of multiple epigenetic pathways, particularly DNA methylation. This stable epigenetic mark suppresses transposable element expression in plants and mammals, serving as an additional layer of chromatin regulation. In this review we explore recent advances in our understanding of the complex interplays between histone variants and DNA methylation in plants, and discuss the role that chromatin remodeling plays in coordinating histone exchange and methylation of DNA.

Advances and challenges in molecular understanding, early detection, and targeted treatment of liver cancer.

In this review, we explore the application of next-generation sequencing in liver cancer research, highlighting its potential in modern oncology. Liver cancer, particularly hepatocellular carcinoma, is driven by a complex interplay of genetic, epigenetic, and environmental factors. Key genetic alterations, such as mutations in TERT, TP53, and CTNNB1, alongside epigenetic modifications such as DNA methylation and histone remodeling, disrupt regulatory pathways and promote tumorigenesis. Environmental factors, including viral infections, alcohol consumption, and metabolic disorders such as nonalcoholic fatty liver disease, enhance hepatocarcinogenesis. The tumor microenvironment plays a pivotal role in liver cancer progression and therapy resistance, with immune cell infiltration, fibrosis, and angiogenesis supporting cancer cell survival. Advances in immune checkpoint inhibitors and chimeric antigen receptor T-cell therapies have shown potential, but the unique immunosuppressive milieu in liver cancer presents challenges. Dysregulation in pathways such as Wnt/β-catenin underscores the need for targeted therapeutic strategies. Next-generation sequencing is accelerating the identification of genetic and epigenetic alterations, enabling more precise diagnosis and personalized treatment plans. A deeper understanding of these molecular mechanisms is essential for advancing early detection and developing effective therapies against liver cancer.

Comprehensive guide for epigenetics and transcriptomics data quality control.

Host response to environmental exposures such as pathogens and chemicals can include modifications to the epigenome and transcriptome. Improved signature discovery, including the identification of the agent and timing of exposure, has been enabled by advancements in assaying techniques to detect RNA expression, DNA base modifications, histone modifications, and chromatin accessibility. The interrogation of the epigenome and transcriptome cascade requires analyzing disparate datasets from multiple assay types, often at single-cell resolution, derived from the same biospecimen. However, there remains a paucity of rigorous quality control standards of those datasets that reflect quality assurance of the underlying assay. This guide outlines a comprehensive suite of metrics that can be used to ensure quality from 11 different epigenetics and transcriptomics assays. Recommended mitigative actions to address failed metrics are provided. The workflow presented aims to improve benchwork protocols and dataset quality to enable accurate discovery of exposure signatures.

A Connection Between the Gut Microbiome and Epigenetic Modification in Age-Related Cancer: A Narrative Review.

As individuals age, physiological changes influence the composition and function of the gut microbiome, significantly impacting the onset and progression of various illnesses, including cancer. Notably, the gut microbiome affects epigenetic modifications such as DNA methylation and histone alterations. Furthermore, it contributes to the age-related decline in immune system efficiency, increasing susceptibility to infections and cancers. This dual role of the gut microbiome-both a protective factor and a risk factor-is a key aspect of its importance in maintaining long-term health, making it a significant topic of discussion in this review. Moreover, a challenge faced by the elderly is the concurrent use of multiple medications. Polypharmacy can interact with the gut microbiome, potentially altering its efficacy, leading to adverse drug reactions, and affecting vital microbiome diversity. The effects of these interactions on cancer therapies and the overall health of elderly patients are becoming increasingly important. Understanding the complex relationship between aging, the gut microbiome, cancer, and polypharmacy is crucial for developing more effective therapeutic strategies and improving patient outcomes. Here, we discuss recent advances in understanding age-related physiological changes in the microbiome and their significance in cancer development and therapy. Specifically, we will explor how epigenetic changes acquired during aging, along with ongoing prescriptions of multiple medications and the decline of immune function, contribute to the intricate relationship between aging and cancer.

Epigenomics-guided precision oncology: Chromatin variants in prostate tumor evolution.

Prostate cancer is a common malignancy that in 5%-30% leads to treatment-resistant and highly aggressive disease. Metastasis-potential and treatment-resistance is thought to rely on increased plasticity of the cancer cells-a mechanism whereby cancer cells alter their identity to adapt to changing environments or therapeutic pressures to create cellular heterogeneity. To understand the molecular basis of this plasticity, genomic studies have uncovered genetic variants to capture clonal heterogeneity of primary tumors and metastases. As cellular plasticity is largely driven by non-genetic events, complementary studies in cancer epigenomics are now being conducted to identify chromatin variants. These variants, defined as genomic loci in cancer cells that show changes in chromatin state due to the loss or gain of epigenomic marks, inclusive of histone post-translational modifications, DNA methylation and histone variants, are considered the fundamental units of epigenomic heterogeneity. In prostate cancer chromatin variants hold the promise of guiding the new era of precision oncology. In this review, we explore the role of epigenomic heterogeneity in prostate cancer, focusing on how chromatin variants contribute to tumor evolution and therapy resistance. We therefore discuss their impact on cellular plasticity and stochastic events, highlighting the value of single-cell sequencing and liquid biopsy epigenomic assays to uncover new therapeutic targets and biomarkers. Ultimately, this review aims to support a new era of precision oncology, utilizing insights from epigenomics to improve prostate cancer patient outcomes.

Leveraging Epigenetic Alterations in Pancreatic Ductal Adenocarcinoma for Clinical Applications.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by late detection and poor prognosis. Recent research highlights the pivotal role of epigenetic alter- ations in driving PDAC development and progression. These changes, in conjunction with genetic mutations, contribute to the intricate molecular landscape of the disease. Specific modifications in DNA methylation, histone marks, and non-coding RNAs are emerging as robust predictors of disease progression and patient survival, offering the potential for more precise prognostic tools compared to conventional clinical staging. Moreover, the detection of epigenetic alterations in blood and other non-invasive samples holds promise for earlier diagnosis and improved manage- ment of PDAC. This review comprehensively summarises current epigenetic research in PDAC and identifies persisting challenges. These include the complex nature of epigenetic profiles, tumour hetero- geneity, limited access to early-stage samples, and the need for highly sensitive liquid biopsy technologies. Addressing these challenges requires the standardisation of methodologies, integra- tion of multi-omics data, and leveraging advanced computational tools such as machine learning and artificial intelligence. While resource-intensive, these efforts are essential for unravelling the functional consequences of epigenetic changes and translating this knowledge into clinical appli- cations. By overcoming these hurdles, epigenetic research has the potential to revolutionise the management of PDAC and improve patient outcomes.

On the Role of Epigenetic Modifications of HPA Axis in Post Traumatic Stress Disorder (PTSD) and Resilience.

Stress is a fundamental adaptive response mediated by the amygdala and Hypothalamus-Pituitary-Adrenal (HPA) axis. Extreme or chronic stress, however, can result in a multitude of neuropsychiatric disorders, including anxiety, paranoia, bipolar disorder (BP), major depressive disorder (MDD), and Post-Traumatic Stress Disorder (PTSD). Despite widespread exposure to trauma (70.4%), the incidence of PTSD is relatively low (6.8%), suggesting that either individual susceptibility or adaptability driven by epigenetic and genetic mechanisms are likely at play. PTSD takes hold from exposure to traumatic events, such as death threats or severe abuse, with its severity being impacted by the magnitude of trauma, it's frequency, and the nature. This comprehensive review examines how traumatic experiences and epigenetic modifications in hypothalamic pituitary axis (HPA), such as DNA methylation, histone modifications, non-coding RNAs, and chromatin remodeling, are transmitted across generations, and impact genes like FKBP5, NR3C1, BDNF, and SLC6A4. It also provides a comprehensive overview on trauma reversal, resilience mechanisms, and pro-resilience factors such as HATs/HDACs ratio, DHEA/Cortisol ratio, testosterone levels, and neuropeptide Y, thus highlighting potential therapeutic approaches for trauma-related disorders. The studies highlighted here underscore the narrative, for the first time, that the examination and treatment of PTSD and other depressive disorders must invoke a multitude of approaches to seek out the most effective and personalized strategies. We also hope that the discussion emanating from this review will also inform government policies directed towards intergenerational trauma and PTSD.

Epigenetic modulation by oncolytic viruses: Implications for cancer therapeutic efficacy.

Among various therapeutic agents, Oncolytic Viruses (OVs) are the most promising anticancer therapeutics because of their tumor-specific targeting and capability to mediate an antitumor immune response. In this review, we will discuss how epigenetic reprogramming of both the host and tumor can facilitate increased sensitivity of tumors to OV therapy. OVs infect tumor cells and modulate epigenetic landscapes, including DNA methylation, histone modifications, and chromatin remodeling, as well as non-coding RNA expression that consequently induces immune responses. These epigenetic changes, including hypermethylation of tumor-associated antigen genes and chromatin accessibility alterations, enhance the immunogenicity of tumors to facilitate recognition by the immune system. Here, we provide a general review addressing this question by discussing the potential benefits of combining OVs with epigenetic drugs to combat resistance and promote treatment efficacy. This information illustrates the importance of personalized OV therapy regarding epigenome in individual profiles and transitions. Still, it extends difficulty in inducing with acquisitions of viral-induced changes globally and making translatable steps by creating cancer-specific predictive treatment models.

Solution conformational differences between conventional and CENP-A nucleosomes are accentuated by reversible deformation under high pressure.

Solution-based interrogation of the physical nature of nucleosomes has its roots in X-ray and neutron scattering experiments, including those that provided the initial observation that DNA wraps around core histones. In this study, we performed a comprehensive small-angle scattering study to compare canonical nucleosomes with variant centromeric nucleosomes harboring the histone variant, CENP-A. We used nucleosome core particles (NCPs) assembled on an artificial positioning sequence (Widom 601) and compared these to those assembled on a natural α-satellite DNA cloned from human centromeres. We establish the native solution properties of octameric H3 and CENP-A NCPs using analytical ultracentrifugation (AUC), small-angle X-ray scattering (SAXS), and contrast variation small-angle neutron scattering (CV-SANS). Using high-pressure SAXS (HP-SAXS), we discovered that both histone identity and DNA sequence have an impact on the stability of octameric nucleosomes in solution under high pressure (300 MPa), with evidence of reversible unwrapping in these experimental conditions. Both canonical nucleosomes harboring conventional histone H3 and their centromeric counterparts harboring CENP-A have a substantial increase in their radius of gyration, but this increase is much less prominent for centromeric nucleosomes. More broadly for chromosome-related research, we note that as HP-SAXS methodologies expand in their utility, we anticipate this will provide a powerful solution-based approach to study nucleosomes and higher-order chromatin complexes.

Unveiling the Conformational Dynamics of the Histone Tails Using Markov State Modeling.

The nucleosome is the fundamental repeat unit of chromatin, composed of a histone octamer and DNA. Each histone has a globular core and N-terminal tail regions. N-terminal tails are major sites for post-translational modifications, chromatin structure, and gene regulation. Using all-atom molecular dynamics simulations of the nucleosome to examine the dynamics of histone tails and analyze the effects of one of the histone modifications, such as acetylation on histone tails. We explore tail dynamics and kinetics using Markov State Models (MSMs) to gain insight into histone tail structural changes. Acetylation of the H2B tail shows an increased dynamics of the tail based on transition rates. Our study characterizes transition rates of all histone tails that can influence nucleosome plasticity and gene regulation.