Epigenomes最新文献

Heavy metal and metalloid stress, particularly from toxic elements like cadmium (Cd), poses a growing threat to plant ecosystems, crop productivity, and global food security. Elevated concentrations of these contaminants can trigger cytotoxic and genotoxic effects in plants, severely impairing growth, development, and reproduction. In recent years, epigenetic mechanisms have emerged as crucial regulators of plant responses to heavy metal stress, offering novel insights and strategies for enhancing plant resilience in contaminated environments. This review synthesises current advances in the field of plant epigenetics, focusing on key modifications such as DNA methylation, histone acetylation and remodelling, chromatin dynamics, and small RNA-mediated regulation. These processes not only influence gene expression under metal-induced stress but also hold promise for long-term adaptation through transgenerational epigenetic memory. Recent developments in high-throughput sequencing and functional genomics have accelerated the identification of epigenetic markers associated with stress tolerance, enabling the integration of these markers into breeding programs and targeted epigenome editing strategies. Special attention is given to cadmium stress responses, where specific epigenetic traits have been linked to enhanced tolerance. As plant epigenomic research progresses, its application in sustainable agriculture becomes increasingly evident offering environmentally friendly solutions to mitigate the impact of heavy metal pollution. This review provides a foundation for future research aimed at leveraging epigenetic tools to engineer crops capable of thriving under metal stress, thereby contributing to resilient agricultural systems and sustainable food production.

Lysine methylation is a critical post-translational modification catalyzed by lysine methyltransferases (KMTs), originally characterized in the regulation of histones. However, the breadth of non-histone targets remains largely unexplored. Here, we used a systematic peptide array-based approach to define a substrate preference motif for the SET-domain-containing KMT MLL4 (KMT2D), a member of the COMPASS complex and a known H3K4 methyltransferase. Using this motif, we identified CXXC finger protein 1 (CFP1), a core component of Setd1A/B complexes, as a putative MLL4 substrate. In vitro methyltransferase assays confirmed robust methylation of CFP1 by an MLL4-WRAD complex. Surprisingly, while initial predictions implicated K328, array-based methylation profiling revealed multiple lysine residues within CFP1's lysine-rich basic domain as methylation targets, including K331, K335, K339, and K340. We further demonstrated that CFP1 methylation likely modulates its interaction with MLL4's PHD cassettes and facilitates binding to Setd1A. Binding preferences of MLL4's PHD1-3 and PHD4-6 domains varied with methylation state and site, suggesting non-histone methyl mark recognition by these cassettes. Pulldown assays confirmed that methylated, but not unmethylated, CFP1 binds Setd1A, supporting a potential methyl-switch mechanism. Together, our findings propose CFP1 as a potential non-histone substrate of MLL4 and suggest that MLL4 may regulate Setd1A/B function indirectly via CFP1 methylation. This study expands the substrate landscape of MLL4 and lays the groundwork for future investigations into non-histone methylation signaling in chromatin regulation.

N6-methyladenosine (m⁶A) is the most abundant and dynamic RNA modification in eukaryotic messenger and non-coding RNAs, playing a pivotal role in the post-transcriptional regulation of gene expression. The coordinated actions of m⁶A writers, erasers, and readers influence transcript stability, immune activation, and pathogen suppression. Growing evidence indicates that m⁶A fine-tunes the expression of defense-related genes, modulates RNA processing events, and is frequently hijacked by pathogens and pests to promote virulence. Notably, the dual role of m⁶A in enhancing plant defense and facilitating pathogen adaptation highlights its significance in the host-pathogen arms race. This review emphasizes recent advances in our understanding of m⁶A-mediated epitranscriptomic regulation in plants, with a focus on its role in responses to biotic stresses, including fungi, bacteria, virus infections, insects, and nematode attacks. This regulatory layer offers novel opportunities for crop protection through targeted manipulation of the epitranscriptomic mechanism.

Background: Heart disease may take a greater toll on Black Americans than White Americans despite similar levels of traditional risk factors. Elevated alcohol consumption (EAC) and chronic inflammation are two potentially important additional risk factors to consider. Both are relevant to understanding health disparities in cardiovascular health.

Methods: Couples with a Black preadolescent or early adolescent child living in the home were recruited and followed. In waves 5 and 6 of data collection, biological samples were also collected allowing the characterization of elevated alcohol consumption, chronic inflammation, and cardiac risk using DNA methylation indices. 383 individual partners comprising 221 couples were examined across the two waves of data, yielding 661 person-wave observations from 383 individuals.

Results: EAC at wave 5 forecast increased cardiac risk at W6 (R² change = 0.276), β = -0.193, p = 0.001. However, chronic inflammation at wave 5 did not add significantly to the baseline model, β = -0.042, p = 0.549. Conversely, the slope of change for chronic inflammation was associated with slope of change in cardiac risk (R² change = 0.111), b = -0.014, p = <0.001, but EAC change was not significantly associated with change in cardiac risk, b = -0.001, p = 0.185.

Conclusions: Elevated alcohol consumption may be an important risk factor for increased cardiac risk over time in middle age. If so, it could be an important avenue for preventative intervention to decrease cardiac risk. Future research should examine whether similar associations are observed for other racial or minoritized groups and for non-minoritized groups.

Background: Posttraumatic growth (PTG) refers to positive psychological change following trauma. While its psychological aspects are well-documented, the biological mechanisms remain unclear. Epigenetic changes, such as DNA methylation (DNAm), may offer insight into PTG's neurobiological basis.

Aims: This study aimed to identify epigenetic markers associated with PTG using an epigenome-wide association study (EWAS), the first of its kind in a trauma-exposed population.

Methods: A longitudinal EWAS design was used to assess DNAm before and after trauma exposure in first-year paramedicine students (n = 39). Genome-wide methylation data were analyzed for associations with PTG, applying epigenome-wide and gene-wise statistical thresholds. Pathway enrichment analysis was also conducted.

Results: The study identified two CpGs (cg09559117 and cg05351447) within the PCDHA1/PCDHA2 and PDZD genes significantly associated with PTG at the epigenome-wide threshold (p < 9.42 × 10^-8); these were replicated in an independent sample. DNAm in 5 CpGs across known PTSD candidate genes ANK3, DICER1, SKA2, IL12B and TPH1 were significantly associated with PTG after gene-wise Bonferroni correction. Pathway analysis revealed that PTG-associated genes were overrepresented in the Adenosine triphosphate Binding Cassette (ABC) transporters pathway (p = 2.72 × 10^-4).

Conclusions: These results identify genes for PTG, improving our understanding of the neurobiological underpinnings of PTG.

Aging of the central nervous system (CNS) involves widespread transcriptional and structural remodeling, prominently marked by synaptic loss, impaired neurogenesis, and glial dysfunction. While age-related gene expression changes have been documented for decades, recent genome-wide next-generation sequencing studies emphasize the importance of epigenetic mechanisms-such as DNA methylation and histone modification-in shaping these profiles. Notably, these modifications are potentially reversible, making them promising targets for therapeutic intervention. However, the mechanisms by which age-associated factors, such as inflammation and oxidative stress, orchestrate these epigenetic alterations across distinct CNS cell types remain poorly understood. In this review, we propose a framework for understanding how aging and neuroinflammation are regulated by epigenetic mechanisms, contributing to brain dysfunction and disease vulnerability.

Background: The role of circulatory miRNAs in gestational diabetes mellitus (GDM) was explored extensively in previous studies. However, there was limited literature on longitudinal studies exploring the changes in miRNA expression during pregnancy and postpartum to understand the changes in their expression levels in GDM patients. Methods: Blood samples from thirty GDM subjects and twenty normoglycemic pregnant women (NGT) were collected between 24 and 28 weeks of their pregnancy, and follow-up samples from the same subjects were collected till 12 weeks postpartum (FGDM and FNGT, respectively). Three candidate miRNAs, hsa-miR-16-5p, hsa-miR-17-5p, and hsa-miR-20a-5p, were quantified from their plasma samples using RT-qPCR. Comparative analysis of these miRNA expression levels was made between different groups. Results: hsa-miR-16-5p, hsa-miR-17-5p, and hsa-miR-20a-5p expression were significantly higher in GDM patients when compared to NGT subjects. Interestingly, hsa-miR-17-5p has shown consistent upregulation in FGDM even after these patients turned normoglycemic. Additionally, hsa-miR-16-5p was found to be higher in FGDM patients compared to FNGT subjects. Conclusions: The present study corroborated the finding of differential expression of hsa-miR-16-5p, hsa-miR-17-5p, and hsa-miR-20a-5p in GDM. It also marked the importance of monitoring the levels of hsa-miR-17-5p and hsa-miR-16-5p during pregnancy and postpartum in GDM patients.

N⁶-methyladenosine (m⁶A) is the most prevalent internal modification in eukaryotic messenger RNA (mRNA) and plays a vital role in post-transcriptional gene regulation. In recent years, m⁶A has emerged as a pivotal epitranscriptomic signal involved in neural development, synaptic remodeling, and the molecular pathophysiology of neuropsychiatric disorders. In this review, we summarize the mechanisms underlying the deposition, removal, and recognition of m⁶A by dedicated methyltransferases, demethylases, and RNA-binding proteins. We further explore how these dynamic modifications influence neuronal differentiation and memory formation. Recent studies have linked aberrant m⁶A regulation to psychiatric conditions such as depression, anxiety, schizophrenia, and bipolar disorder. Additionally, we discuss how pharmacological or genetic modulation of m⁶A pathways may promote adaptive neural plasticity and enhance cognitive and emotional resilience. Despite these promising findings, significant challenges remain in achieving spatial and temporal specificity while minimizing off-target effects in the brain. Therefore, we advocate for more in-depth investigations into m⁶A function within developmentally defined neural circuits to better understand its enduring role in maintaining neural homeostasis.

Background/objectives: The DNA methylome allows environmental signals to be converted into stable and adaptive changes in gene expression. While 5-methylcytosine (5mC) has been extensively studied, alternative epigenetic marks such as N6-methyladenine (6mA) and 5-hydroxymethylcytosine (5hmC) remain poorly understood. Comparative studies of these marks are rare, and their results are often confounded by phylogeny, tissue type, developmental stage, or methodology. Here, we aimed to disentangle the constitutive, somatic- and germline-specific, and/or age-related patterns displayed by 6mA, 5mC, and 5hmC within a single species.

Methods: We generated long-read nanopore sequencing data for somatic tissues of buff-tailed bumblebee (Bombus terrestris) males and their sperm, enabling simultaneous detection of 6mA, 5mC, and 5hmC. We used a stepwise approach to successively identify (i) constitutive patterns conserved between somatic tissues and sperm, (ii) differences between the soma and the germline, and (iii) age-related changes between young and old males.

Results: We found distinct constitutive, somatic and sperm, and age-related specific signatures in the genomic contexts, maintenance fidelity, and biological functions associated with 6mA, 5mC, and 5hmC. Sperm cells consistently displayed lower methylation entropy than did somatic tissues, indicating more stable methylation patterns in the germline. 5mC exhibited the greatest variation across all genomic contexts; 6mA and 5hmC displayed less dramatic differences. The influence of age was subtler but revealed context-dependent remodeling of methylation, particularly for 5hmC.

Conclusions: We observed that 6mA, 5mC, and 5hmC displayed constitutive, somatic- and sperm-specific, and age-related differences that were associated with distinct genomic contexts and biological functions, supporting the complementarity of these methylation marks and their diverging epigenetic roles.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous malignancy, characterized by low tumor cellularity, a dense stromal response, and intricate cellular and molecular interactions within the tumor microenvironment (TME). Although bulk omics technologies have enhanced our understanding of the molecular landscape of PDAC, the specific contributions of non-malignant immune and stromal components to tumor progression and therapeutic response remain poorly understood. Methods: We explored genome-wide DNA methylation and transcriptomic data from the Cancer Genome Atlas Pancreatic Adenocarcinoma cohort (TCGA-PAAD) to profile the immune composition of the TME and uncover gene co-expression networks. Bioinformatic analyses included DNA methylation profiling followed by hierarchical deconvolution, epigenetic age estimation, and a weighted gene co-expression network analysis (WGCNA). Results: The unsupervised clustering of methylation profiles identified two major tumor groups, with Group 2 (n = 98) exhibiting higher tumor purity and a greater frequency of KRAS mutations compared to Group 1 (n = 87) (p < 0.0001). The hierarchical deconvolution of DNA methylation data revealed three distinct TME subtypes, termed hypo-inflamed (immune-deserted), myeloid-enriched, and lymphoid-enriched (notably T-cell predominant). These immune clusters were further supported by co-expression modules identified via WGCNA, which were enriched in immune regulatory and signaling pathways. Conclusions: This integrative epigenomic-transcriptomic analysis offers a robust framework for stratifying PDAC patients based on the tumor immune microenvironment (TIME), providing valuable insights for biomarker discovery and the development of precision immunotherapies.