Search Results (353)

Lysine succinylation is a recently discovered post-translational protein modification, the process of which requires the participation of various enzymes. The close association between cancer and protein post-translational modifications (PTMs), such as acetylation and phosphorylation, has been extensively investigated and well-established. In recent years, growing attention has been directed toward the role of succinylation in cancer progression. Accumulating evidence demonstrates that protein succinylation and desuccinylation play critical roles in promoting the development of various cancers, including lung, prostate, and renal cancers. Notably, the primary substrates undergoing succinylation are non-histone proteins. Therefore, elucidating the functions of cancer-related succinylated proteins is essential for identifying novel therapeutic targets. This review comprehensively summarizes current research advances regarding protein succinylation in common cancers and discusses the progress in developing succinylation-targeting drugs. Specifically, we focus on the molecular mechanisms by which succinylation regulates cancer progression, along with the identification of key succinylation sites. Our discussion aims to provide valuable insights for future research and the development of innovative cancer treatments. Full article

Protein acetylation, a conserved post-translational modification, is collaboratively catalyzed by acetyltransferases and deacetylases and is widespread in plants. This study reviews recent research regarding two key types of acetylation: histone acetylation and non-histone acetylation. Histone acetylation, occurring primarily in the nucleus, regulates the structure of chromatin to control gene transcription on a large scale. This process is crucial for the precise regulation of the plant organ formation and development. Non-histone protein acetylation is widely distributed across various organelles and can finely regulate almost all key cellular processes and functions. Histone and non-histone acetylation work together to construct a complex and precise acetylation-modification regulatory network in plants. Finally, this study also analyzes current research challenges and prospects related to acetylation modifications. Elucidating the regulatory mechanisms of acetylation modifications in plants not only enables us to better understand the molecular mechanisms of plant growth and development but also provides a theoretical basis and potential targets for the genetic improvement and enhancement of stress resistance in crops, with significant scientific and practical value. Full article

Age-related macular degeneration (AMD) is one of the leading causes of irreversible vision loss among the elderly, and is influenced by a combination of genetic and environmental risk factors. While genetic associations in AMD are well-established, the molecular mechanisms underlying disease onset and progression remain poorly understood. A growing body of evidence suggests that epigenetic modifications may serve as a potential missing link regulating gene–environment interactions. This review incorporates recent findings on DNA methylation, including both hypermethylation and hypomethylation patterns affecting genes such as silent mating type information regulation 2 homolog 1 (SIRT1), glutathione S-transferase isoform (GSTM), and SKI proto-oncogene (SKI), which may influence key pathophysiological drivers of AMD. We also examine histone modification patterns, chromatin accessibility, the status of long non-coding RNAs (lncRNAs) in AMD pathogenesis and in regulating pathways pertinent to the pathophysiology of the disease. While the field of ocular epigenetics remains in its infancy, accumulating evidence to date points to a burgeoning role for epigenetic regulation in AMD, pre-clinical studies have yielded promising findings for the prospect of epigenetics as a future therapeutic avenue. Full article

Ferroptosis is a distinct form of regulated cell death driven by iron-dependent lipid peroxidation participating in various diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a central regulator of cellular redox homeostasis and a key determinant of ferroptosis resistance. Nrf2 activates the expression of downstream antioxidant genes to protect cells from oxidative stress and ferroptosis. Consequently, precise regulation of Nrf2 expression is crucial. Recent studies have revealed that complex epigenetic mechanisms involving DNA methylation, histone modifications, and non-coding RNA networks regulate Nrf2 expression. DNA methylation usually suppresses while histone acetylation promotes Nrf2 expression. The influences of histone methylation on NFE2L2 are site- and methylation degree-dependent. m6A modification stabilizes NFE2L2 mRNA to promote Nrf2 expression and thereby inhibit ferroptosis. This article summarizes current understanding of the epigenetic mechanisms controlling Nrf2 expression and Nrf2-mediated ferroptosis pathways and their implications in disease models. The challenges associated with the epigenetic regulation of Nrf2 and future research directions are also discussed. A comprehensive understanding of this regulatory interplay could open new avenues for intervention in ferroptosis-related diseases by fine-tuning cellular redox balance through the epigenetic modulation of Nrf2. Full article

Among the numerous compounds released as a result of human activities, endocrine-disrupting chemicals (EDCs) have attracted particular attention due to their widespread detection in human biological samples and their accumulation across various ecosystems. While early research primarily focused on their effects on reproductive health, it is now evident that EDCs may impact neurodevelopment, altering the integrity of neural circuits essential for cognitive abilities, emotional regulation, and social behaviors. These compounds may elicit epigenetic modifications, such as DNA methylation and histone acetylation, that result in altered expression patterns, potentially affecting multiple generations and contribute to long-term behavioral phenotypes. The effects of EDCs may occur though both direct and indirect mechanisms, ultimately converging on neurodevelopmental vulnerability. In particular, the gut–brain axis has emerged as a critical interface targeted by EDCs. This bidirectional communication network integrates the nervous, immune, and endocrine systems. By altering the microbiota composition, modulating immune responses, and triggering epigenetic mechanisms, EDCs can act on multiple and interconnected pathways. In this context, elucidating the impact of EDCs on neurodevelopmental processes is crucial for advancing our understanding of their contribution to neurological and behavioral health risks. Full article

Acute respiratory distress syndrome (ARDS) is an inflammatory pulmonary condition that remains at alarming rates of fatality, with neutrophils playing a vital role in its pathogenesis. Beyond their classical antimicrobial functions, neutrophils contribute to pulmonary injury via the release of reactive oxygen species, proteolytic enzymes, and neutrophil extracellular traps (NETs). To identify targets for treatment, it was found that epigenetic mechanisms, including histone modifications, hypomethylation, hypermethylation, and non-coding RNAs, regulate neutrophil phenotypic plasticity, survival, and inflammatory potential. It has been identified that neutrophils in ARDS patients exhibit abnormal methylation patterns and are associated with altered gene expression and prolonged neutrophil activation, thereby contributing to sustained inflammation. Histone citrullination, particularly via PAD4, facilitates NETosis, while histone acetylation status modulates chromatin accessibility and inflammatory gene expression. MicroRNAs have also been shown to regulate neutrophil activity, with miR-223 and miR-146a potentially being biomarkers and therapeutic targets. Neutrophil heterogeneity, as evidenced by distinct subsets such as low-density neutrophils (LDNs), varies across ARDS etiologies, including COVID-19. Single-cell RNA sequencing analyses, including the use of trajectory analysis, have revealed transcriptionally distinct neutrophil clusters with differential activation states. These studies support the use of epigenetic inhibitors, including PAD4, HDAC, and DNMT modulators, in therapeutic intervention. While the field has been enlightened with new findings, challenges in translational application remain an issue due to species differences, lack of stratification tools, and heterogeneity in ARDS presentation. This review describes how targeting neutrophil epigenetic regulators could help regulate hyperinflammation, making epigenetic modulation a promising area for precision therapeutics in ARDS. Full article

Wharton’s jelly mesenchymal stem cells (WJ-SCs) are a promising source for regenerative medicine due to their multipotency, low immunogenicity, and ethical acceptability. Epigenetic regulation plays a crucial role in modulating their proliferation, differentiation, and therapeutic potential. Key mechanisms, including DNA methylation, histone modifications, and non-coding RNAs (e.g., miRNAs and lncRNAs), influence WJ-SC behavior by dynamically altering gene expression without changing the DNA sequence. DNA methylation often silences genes involved in differentiation, while histone acetylation/methylation can activate or repress lineage-specific pathways. Non-coding RNAs further fine-tune these processes by post-transcriptional regulation. Understanding these mechanisms could optimize WJ-SC-based therapies for tissue repair and immune modulation. This review summarizes current insights into epigenetic regulation in WJ-SCs and its implications for regenerative applications. Full article

Aurora kinase B (AURKB), a serine/threonine protein kinase, is essential for accurate chromosome segregation and cytokinesis during mitosis. Dysregulation of AURKB, often characterized by its overexpression, has been implicated in various malignancies, including breast cancer. However, the mechanisms governing its dysregulation remain incompletely understood. Here, we identify a pivotal role for the MOF/MSL complex—which includes the histone acetyltransferase MOF (KAT8)—in modulating AURKB stability through acetylation at lysine 215 (K215). This post-translational modification inhibits AURKB ubiquitination, thereby stabilizing its protein levels. MOF/MSL-mediated AURKB stabilization promotes the proper assembly of the chromosomal passenger complex (CPC), ensuring mitotic fidelity. Notably, inhibition of MOF reduces AURKB K215 acetylation, leading to decreased AURKB expression and activity. Consequently, this downregulation suppresses expression of the downstream oncogene c-MYC, ultimately attenuating the malignant proliferation of breast cancer cells. Collectively, our findings reveal a novel mechanism by which lysine acetylation regulates AURKB stability, highlight the significance of the MOF-AURKB-c-MYC axis in breast cancer progression, and suggest potential therapeutic strategies targeting this pathway in clinical settings. Full article

Background: Epigenomic instability accelerates mutations in tumor suppressor genes and oncogenes, contributing to malignant transformation. Histone modifications, particularly methylation and acetylation, significantly influence tumor biology, with chromo-, bromo-, and Tudor domain-containing proteins mediating these changes. This study investigates how genes encoding these domain-containing proteins affect colorectal cancer (CRC) prognosis. Methods: Using CRC data from the GSE39582 and TCGA datasets, we identified domain-related genes via GeneCards and developed a prognostic signature using LASSO-COX regression. Patients were classified into high- and low-risk groups, and comparisons were made across survival, clinical features, immune cell infiltration, immunotherapy responses, and drug sensitivity predictions. Single-cell analysis assessed gene expression in different cell subsets. Results: Four domain-related genes (AKAP1, ORC1, CHAF1A, and UHRF2) were identified as a prognostic signature. Validation confirmed their prognostic value, with significant differences in survival, clinical features, immune patterns, and immunotherapy responses between the high- and low-risk groups. Drug sensitivity analysis revealed top candidates for CRC treatment. Single-cell analysis showed varied expression of these genes across cell subsets. Conclusions: This study presents a novel prognostic signature based on domain-related genes that can predict CRC severity and offer insights into immune dynamics, providing a promising tool for personalized risk assessment in CRC. Full article

Epigenetic modifications act as crucial regulators of gene activity and are influenced by both internal and external environmental factors, with diet being the most impactful external factor. On the other hand, cellular metabolism encompasses a complex network of biochemical reactions essential for maintaining cellular function, and it impacts every cellular process. Many metabolic cofactors are critical for the activity of chromatin-modifying enzymes, influencing methylation and the global acetylation status of the epigenome. For instance, dietary nutrients, particularly those involved in one-carbon metabolism (e.g., folate, vitamins B12 and B6, riboflavin, methionine, choline, and betaine), take part in the generation of S-adenosylmethionine (SAM), which represents the main methyl donor for DNA and histone methylation; α-ketoglutarate and ascorbic acid (vitamin C) act, respectively, as a co-substrate and cofactor for Ten-eleven Translocation (TET), which is responsible for DNA demethylation; and metabolites such as Acetyl-CoA directly impact histone acetylation, linking metabolism of the TCA cycle to epigenetic regulation. Further, bioactive compounds, such as polyphenols, modulate epigenetic patterns by affecting methylation processes or targeting epigenetic enzymes. Since diet and nutrition play a critical role in shaping epigenome functions and supporting human health, this review offers a comprehensive update on recent advancements in metabolism, epigenetics, and nutrition, providing insights into how nutrients contribute to metabolic balance, epigenome integrity maintenance and, consequently, disease prevention. Full article

Mitochondria maintain cellular homeostasis through the dynamic balance of fusion and fission, which relies on nuclear-encoded mitochondrial fusion proteins, mitofusins 1 and 2 (Mfn1, Mfn2). Changes in Mfn1 and Mfn2 expression significantly affect mitochondrial fusion and fission, thereby affecting cellular metabolism. This study investigated the effect of Mfn1 expression on cell proliferation, apoptosis, and mitochondrial function by overexpressing Mfn1 (in OE-Mfn1 cells) and silencing Mfn1 using short hairpin RNA (shRNA) (in shMfn1 cells). Cell proliferation capacity, mitochondrial membrane potential, and mitochondrial ATP content were measured. To investigate the effects of Mfn1 on cellular metabolism and epigenetic modifications, the levels of metabolites α-KG, A-CoA, and SAM, as well as the levels of cellular methylation and acetylation, were detected by ELISA. Differentially expressed genes and metabolites were assessed by RNA-seq and LC-MS. This study demonstrates that alterations in Mfn1 gene expression can significantly affect mitochondrial metabolism and cell proliferation and apoptosis. In addition, Mfn1 affects the expression of genes encoding enzymes that are responsible for histone methylation and acetylation, thereby regulating these modifications. These findings provide a theoretical basis for further elucidation of the mechanisms by which Mfn1 affects cell proliferation, regulates metabolites, and modulates chromatin epigenetic modification. Full article

Traumatic injuries to the peripheral (PNS) and central nervous systems (CNS) trigger distinct regenerative responses, with the PNS displaying limited regenerative capacity and the CNS remaining largely refractory. Recent research highlights the role of epigenetic modifications, particularly histone acetylation, in modulating the gene expression programs that drive axonal regeneration. This review synthesizes current findings on post-translational histone modifications, focusing on histone acetyltransferases (HATs), histone deacetylases (HDACs), and epigenetic readers, in addition to their impact on neuronal and non-neuronal cells following injury. While HATs like p300/CBP and PCAF promote the expression of regeneration-associated genes, HDAC inhibition has been shown to facilitate neurite outgrowth, neuroprotection, and functional recovery in both PNS and CNS models. However, HDAC3, HDAC5, and HDAC6 demonstrate context- and cell-type-specific roles in both promoting and limiting regenerative processes. The review also highlights cell-specific findings that have been scarcely covered in the previous literature. Thus, the immunomodulatory roles of epigenetic regulators in microglia and macrophages, their involvement in remyelination via Schwann cells and oligodendrocytes, and their impact on astrocyte function are within the scope of this review. Closely considering cell-context specificity is critical, as some targets can exert opposite effects depending on the cell type involved. This represents a major challenge for current pharmacological therapies, which often lack precision. This complexity underscores the need to develop strategies that allow for cell-specific delivery or target regulators with converging beneficial effects across cell types. Such approaches may enhance regenerative outcomes after CNS or PNS injury. Full article

The retinal pigment epithelium (RPE) is a cellular source of retinal regeneration in lower vertebrates and a cellular source of retinal diseases in mammals, including humans. Both processes are based on a genetic program for the conversion of RPE cells into cells of other phenotypes: neural in the first case and mesenchymal in the second. RPE reprogramming in the neural direction is realized in tailed amphibians and bird embryos in vivo, but in higher vertebrates and humans, this process is realized in vitro. Epigenetic regulation determines the phenotypic plasticity of RPE cells, i.e., their choice of the cell differentiation pathway in animals of different classes. It has been suggested that the implementation of the genetic program for RPE reprogramming into different types of retinal neurons in adult amphibians and birds at the early stages of embryogenesis is conditioned by the specificity of the epigenetic landscape. The retinal RPE-dependent pathologies in mammals are characterized by different epigenetic signatures, and have a shared characteristic: specifically, a deficient epigenetic landscape (dysregulations in DNA methylation and histone modifications). Knowledge of the patterns and features of the epigenetic regulation of RPE cell behavior will allow us to obtain RPE cells that are in demand in medicine, from direct reprogramming with the possibility of epigenetically maintaining the cellular identities to the creation of neuro-regenerative technologies for the replacement therapy of RPE-dependent retinal pathologies in humans. Full article

Recent investigations into the neuroepigenome of the brain are providing unparalleled understanding into the impact of post-translational modifications (PTMs) of histones in regulating dynamic gene expression patterns required for adult brain cognitive function and plasticity. Histone acetylation is one of the most well-characterized PTMs shown to be required for neuronal function and cognition. Histone acetylation initiates neural circuitry plasticity via chromatin control, enabling neurons to respond to external environmental stimuli and adapt their transcriptional responses accordingly. While interplay between histone acetylation and deacetylation is critical for these functions, dysregulation during the aging process can lead to significant alterations in the neuroepigenetic landscape. These alterations contribute to impaired cognitive functions, neuronal cell death, and brain atrophy, all hallmarks of age-related neurodegenerative disease. Significantly, while age-related generation of DNA mutations remains irreversible, most neuroepigenetic PTMs are reversible. Thus, manipulation of the neural epigenome is proving to be an effective therapeutic strategy for neuroprotection in multiple types of age-related neurodegenerative disorders (NDs) that include Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD). Here, we highlight recent progress in research focusing on specific HAT-based neuroepigenetic mechanisms that underlie cognition and pathogenesis that is hallmarked in age-related NDs. We further discuss how these findings have potential to be translated into HAT-mediated cognitive-enhancing therapeutics to treat these debilitating disorders. Full article

Fusarium verticillioides is a globally prevalent phytopathogenic fungus responsible for multiple diseases in maize and a major producer of the mycotoxin fumonisin B1 (FB1), a highly toxic fungal secondary metabolite (FSM). The histone code, which includes reversible modifications such as acetylation and methylation, plays a critical role in regulating chromatin structure and gene expression. In fungi, di- and tri-methylation of histone H3 at lysine 9 (H3K9me2/3) serves as a key epigenetic mark associated with heterochromatin formation and transcriptional repression. In this study, we identified and characterized a putative heterochromatin protein 1 (HP1) family member in F. verticillioides, designated FvHP1, based on conserved domain architecture and phylogenetic analyses. FvHP1 retains essential residues required for H3K9me2/3 recognition, supporting its functional conservation within the HP1 protein family. Phenotypic analysis of the ΔFvHP1 mutant revealed impaired vegetative growth, reduced conidiation and virulence, and altered FB1 mycotoxin production. Additionally, the accumulation of red pigment in the mutant was linked to the deregulation of secondary metabolism, specifically the overproduction of fusarubin-type naphthoquinones, such as 8-O-methylnectriafurone. These results support the role of FvHP1 in facultative heterochromatin-mediated repression of sub-telomeric biosynthetic gene clusters, including the pigment-associated PGL1 cluster. Our findings provide new insights into the epigenetic regulation of fungal pathogenicity and metabolite production, as well as the first evidence of a functional HP1 homolog in F. verticillioides. Full article