Epigenomes最新文献

Circular RNAs (circRNAs) are small, non-coding RNAs in which the 5' and 3' ends are linked covalently by back-splicing of exons from a single pre-mRNA. More and more scientific evidence is gathered for their wide distribution in the animal world, playing the role of regulators for biological processes, being cell- and tissue-specific. They can influence cellular physiology by various molecular mechanisms, finally modulating gene expression. CircRNAs are believed nowadays to be expressed in both receptive and cancerous endometrium. Due to their abundant expression in the endometrial tissue and their small size and stability, they have been considered potential diagnostic markers and treatment targets for endometrial-related diseases. The regulation of proliferation and differentiation is essential for the formation of receptive endometrium and for endometrial cancer emergence and progression. The receptive endometrium can be regarded as the most highly differentiated state of the endometrium. In contrast, the cancerous endometrium is characterized by a high level of proliferation and the lowest degree of differentiation. These endometria could be conditionally considered opposites. We are investigating the circRNA-miRNA-mRNA regulatory networks that can promote or suppress the proliferation and differentiation of endometrial cells by activating specific signaling pathways in both receptive and cancerous endometria. It could be worth knowing whether there are universal endometrial switches responsible for proliferation and differentiation processes that can alter the balance between them. We are interested in their clinical application as biomarkers and therapeutic targets for both endometrial receptivity issues and EC cases, particularly in diagnosis, progression assessment, and outcome prediction.

Rice (Oryza sativa L.) is a staple food for over half the global population and a model organism for monocot plant research. However, it is susceptible to salinity, with most cultivated varieties showing reduced growth at salt levels above 3 dS/m. Despite numerous efforts to improve its salt tolerance, little progress has been made. A promising area of research lies in the study of epigenetic regulation, which encompasses DNA methylation, histone modifications, and chromatin remodelling. These processes play a crucial role in mediating how plants respond to salt stress by modulating gene expression. This often results in heritable changes that can be used as molecular markers. Studies in rice and other cereals have demonstrated a clear association between histone alterations, shifts in DNA methylation patterns, and the expression of salt-responsive genes. Furthermore, epigenetic mechanisms contribute to the development of stress memory, enabling plants to respond more effectively to recurring stressful conditions. Understanding these regulatory pathways offers new opportunities for breeding or engineering salt-tolerant rice varieties, potentially leading to improved crop resilience and productivity under saline conditions.

Background: Trait convergence or parallelism is widely seen across the animal and plant kingdoms. For example, the evolution of eyes in cephalopods and vertebrate lineages, wings in bats and insects, or shark and dolphin body shapes are examples of convergent evolution. Such traits develop as a function of environmental pressures or opportunities that lead to similar outcomes despite the independent origins of underlying tissues, cells, and gene transcriptional patterns. Our current understanding of the molecular processes underlying these phenomena is gene-centric and focuses on how convergence involves the recruitment of novel genes, the recombination of gene products, and the duplication and divergence of genetic substrates.

Scope: Despite the independent origins of a given trait, these model organisms still possess some form of epigenetic processes conserved in eukaryotes that mediate gene-by-environment interactions. These traits evolve under similar environmental pressures, so attention should be given to plastic molecular processes that shape gene function along these evolutionary paths. Key Mechanisms: Here, we propose that epigenetic processes such as histone-modifying machinery are essential in mediating the dialog between environment and gene function, leading to trait convergence across disparate lineages. We propose that epigenetic modifications not only mediate gene-by-environment interactions but also bias the distribution of de novo mutations and recombination, thereby channeling evolutionary trajectories toward convergence. An inclusive view of the epigenetic landscape may provide a parsimonious understanding of trait evolution.

Background/Objectives: Histone acetylation regulates gene expression and plays a key role in cancer pathophysiology. Nanotherapeutics are known to modulate histone acetylation and influence cancer progression. This systematic scoping review examines the effects of nanotherapeutics on histone acetylation enrichment across multiple cancers. Methods: A systematic search of Embase, PubMed/MEDLINE, Scopus, and Web of Science was conducted in accordance with the PRISMA 2020 statement. A total of 13 studies were included. Data were analyzed and visualized in R, and risk of bias was assessed with ToxRTool (OSF Registration: 10.17605/OSF.IO/E643S). Results: Nanotherapeutics were most commonly evaluated against breast (21.4%), prostate (21.4%), pancreatic (14.3%), and bladder (14.3%) cancers. Primary nanomaterials used in the synthesis of nanotherapeutics included poly(lactic-co-glycolic acid) (25.0%), gold (21.4%) and arsenic oxide (21.4%) nanoparticles. Studied histone acetylation marks included H3K9ac, H3K14ac, H3K27ac and H4K16ac. Treatment with nanotherapeutics increased histone H3 and H4 acetylation enrichment, particularly H3K14ac in colorectal and prostate cancers and H4K16ac in ovarian cancer. Conversely, gold-based nanotherapeutics decreased H3K9ac and H3K14ac enrichment in breast cancer. The optimal concentration for most nanotherapeutics was ≤25 µM, with PpIX-FFYSV showing the strongest anticancer effect (viability <25%). Across four preclinical studies (n = 58), treatment with the nanotherapeutics reduced tumor size to less than 50% of control in 64% of animals (95% CI: 21-92%, I² = 63.8%). Altered histone acetylation was associated with differential expression of CDKN1A, HSPA1, SREBF2 and TGFB. Conclusions: The evidence demonstrates that nanotherapeutics can alter histone acetylation patterns by modulating EP300/CBP, GCN5 and HDAC, preventing cancer progression and invasion.

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.