Approximately 10% US infants are born small for gestational age (SGA), a condition linked to increased morbidity and mortality. Infants born to Black women are twice as likely to be SGA compared with those born to White women. Although maternal factors, including epigenetic modifications, likely contribute to SGA, the underlying biological mechanisms remain poorly understood. We evaluated whether epigenetic modifications in early pregnancy were associated with SGA among pregnant Black women. We analyzed data from 931 pregnant non-Hispanic Black women (6-13 weeks of gestation) enrolled in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) cohort across eight academic medical centers. We conducted an epigenome-wide association study using the Infinium MethylationEPIC assay on blood samples from women who delivered SGA infants (n = 133) and appropriate for gestational age infants (n = 798). We adjusted for maternal age, prenatal smoking, education, body mass index, and infant sex, and corrected with multiple testing. We identified 14 differentially methylated 5'-C-phosphate-G-3' (CpG) sites mapping to genes involved in placental development, vascular remodeling, and fetal growth regulation. Functional enrichment analysis highlighted the pathways involved in early embryonic development and placental function, implicating early-pregnancy maternal epigenetic alterations in SGA delivery among Black women and supporting DNA methylation profiling as a potential SGA biomarker.
Tumor-specific DNA methylation carried by circulating tumor DNA (ctDNA) is a promising marker for early cancer screening. This study endeavors to create, verify, and deploy a liquid biopsy method based on ctDNA methylation for the early identification of lung cancer (LC). Firstly, we established an LC-specific methylation profile by analyzing the differential expression of DNA methylation between 69 pairs of cancerous and paracancerous healthy tissues. A total of 2,680 differentially methylated positions (DMPs) between lung cancer tissues and paracancerous healthy tissues were identified. Enrichment analysis unveiled associations of these DMPs with various biological processes. The heatmap representation of LC-specific DMPs underscores distinct methylation patterns observed between lung cancer and paracancerous tissues. Subsequently, 127 plasma samples from stage I lung cancer patients and unaffected individuals were split into training and test groups to establish a model incorporating 22 of these LC-specific DMPs. This model yielded an 88.57% sensitivity and 78.43% specificity in the training data, with an area under the curve (AUC) of 0.8913. The corresponding performance in the test set was 60% sensitive and 76.92% specific, with an AUC of 0.7025. These outcomes indicate the promise of ctDNA methylation markers in enhancing the potential for early lung cancer detection.
N6-methyladenosine (m6A) is the predominant internal modification occurring within RNA molecules, but its role in porcine adipogenesis remains poorly understood. A high-quality transcriptome-wide m6A methylation map was therefore generated, and the m6A regulator expression pattern profiled during the differentiation of stromal vascular fraction cells into white adipocytes. It was found that the demethylases FTO and ALKBH5 were highly expressed in mature adipocytes, accompanied by widespread m6A hypo-methylation. The hypo-methylated gene set was enriched with regulators of metabolism and transcription, and their downregulation suggests that demethylation contributes to transcriptional repression during terminal differentiation. Notably, many hypo-methylated and downregulated genes overlapped with cancer-related pathways, including therapeutic targets such as ABL1, BRCA2, MET, and PML. MeRIP-qPCR and RT-qPCR validation confirmed these trends. Together, the present findings demonstrate that m6A demethylation reshapes gene expression to regulate porcine adipocyte differentiation and provides insights into the potential crosstalk between lipid metabolism and oncogenic signaling.
Eucommia ulmoides could produce high-quality trans-polyisoprene (TPI), providing a new and alternative industrial material for natural rubber. However, the molecular mechanisms underlying TPI biosynthesis remain poorly understood. In this study, triploid E. ulmoides plants were generated through polyploid breeding and shower higher TPI content compared to diploid and tetraploid plants. Using real-time PCR analysis, it was found that the expression of two imitation switch (ISWI)-family chromatin remodelers, EuCHR11 and EuCHR17, were downregulated in high-TPI-yielding triploid plants during the period of TPI biosynthesis, whereas the expression of the key rubber biosynthesis gene EuSRPPB was significantly upregulated under the same conditions. In Arabidopsis thaliana, it was demonstrated that the orthologs AtCHR11 and AtCHR17 directly bind to the genomic loci of AtSRPP1, AtSRPP2, and AtSRPP3 and repress their expression. Similarly, EuCHR11 also directly binds to the promoter of EuSRPPB in E. ulmoides. These results together indicate that EuCHR11 and EuCHR17 negatively regulate TPI biosynthesis by repressing EuSRPPB expression. The findings in this study uncover a previously uncharacterized epigenetic regulatory pathway mediated by chromatin remodeling factors that modulates rubber biosynthesis and enhances the understanding of the molecular mechanisms behind rubber production.
Circular ribonucleicacids (circRNAs), marked by their covalently closed-loop structures, serve as crucial regulators in tumor development and progression. This study aimed to explore how circ86591, one of the isoforms of circular ANRIL, affects the progression of colorectal cancer (CRC). Real-time quantitative polymerase chain reaction (qRT-PCR) was utilized to examine circ86591 expression in cells. RNA pull-down, mass spectrometry, RNA immunoprecipitation, and western blotting (WB) were applied to elucidate molecular mechanisms underlying circ86591 and its binding proteins. RNA-sequencing, along with gain-and loss-of function assays, was conducted to uncover the tumor-suppressive effect and the relevant signaling pathways of circ86591. Circ86591 is lowly expressed in CRC cells overexpressing oncogenic linANRIL. Mechanistically, circ86591 directly interacts with ErbB3-binding protein (EBP1) and acetyl coenzyme A carboxylase (ACC1) proteins to modulate cell cycle and lipid metabolism. The knockdown of circ86591 by antisense oligonucleotide (ASO) increases the drug resistance of CRC cells to 5-FU, gemcitabine, or doxorubicin. Overexpression of circ86591 suppresses CRC growth both in vitro and in vivo via upregulation of P53 and negative feedback of the protein kinase B (AKT) pathway. Combining circ86591 adenovirus (ADV) with the anti-lipid metabolism drug CMS121 yields synergistic anti-tumor effects. In conclusion, the circ86591 inhibits CRC progression and holds potential as a therapeutic target for those tumors with active lipid metabolism.
Cultivated strawberry (Fragaria & times; ananassa) is an economically important fruit crop with a complex octoploid genome, which has historically limited genomic and epigenomic analyses. Recent advances in long-read sequencing technologies have enabled the assembly of high-quality telomere-totelomere reference genomes, opening new opportunities for studying epigenetic regulation in this polyploid species. DNA methylation, a heritable epigenetic modification, regulates gene expression and maintains genome stability. In plants, DNA methylation plays crucial roles in seed development, fruit ripening, stress responses, and genome evolution. In this study, whole-genome DNA methylation profiles were generated for two genetically distinct octoploid strawberry cultivars, 'Florida Brilliance', and 'Seolhyang'. Genome-wide analyses showed that while overall methylation patterns were largely conserved, 'Seolhyang' had reduced CHG methylation, especially in transposable elements and certain genes. Genes were grouped into three categories based on genebody methylation: CG genebody methylated, transposon-like methylated, and unmethylated. Notably, the frequency of transposon-like methylated genes was positively correlated with local transposable element density. These categories exhibited distinct expression patterns and varied across subgenomes. Subgenome-level analyses revealed that subgenome A across all seven chromosome sets had the lowest DNA methylation levels and the fewest transposable elements, which may contribute to its dominant gene expression among the subgenomes. Additionally, genes overlapping with transposable elements in subgenome A showed higher expression, indicating that reduced local methylation may promote transcription. This study presents a comprehensive DNA methylation analysis of two genetically and geographically distinct strawberry cultivars and provides new insights into the role of epigenetic regulation in polyploid crops.
DNA methylation and histone modifications are two fundamental epigenetic markers that play pivotal roles in regulating gene expression and maintaining genomic stability in both plant and animal kingdoms. These conserved epigenetic mechanisms are critical in mediating responses to various biotic and abiotic stresses, while simultaneously orchestrating developmental processes and other essential biological functions. This review explores the conserved and divergent regulatory mechanisms of DNA methylation and histone modifications in plants and animals, their synergistic roles in reproductive development, growth regulation, and stress adaptation, as well as the dynamic crosstalk between these epigenetic modifications. This review highlights emerging evidence of the cooperative integration of these epigenetic mechanisms within gene regulatory networks, offering new insights into how they shape phenotypic plasticity. By synthesizing current knowledge across model systems, this review advances the mechanistic understanding of the regulation while providing a conceptual framework for future research in epigenetic breeding, stress resilience engineering, and evolutionary developmental biology. These perspectives pave the way for epigenetics-driven strategies to enhance agricultural productivity and biomedical applications.
N6-methyladenosine (m6A) modification of messenger RNA is crucial for phase separation, regulating diverse developmental and signaling processes in plants. However, the mechanistic and cellular role of plant m6A modification in phase separation is little understood and is just beginning to be explored. Several recent studies have shed new light on m6A readers' function in phase separation during the response to abscisic acid (ABA) and flowering in Arabidopsis and rice. Identification of m6A readers and the interacting proteins undergoing phase separation, and characterization of the structural features of m6A readers that are crucial for phase separation will deepen insights into the significance of RNA modifications in response to developmental stress and phytohormonal signals in plants.
Osteoarthritis (OA), characterized by the whole joint degeneration, is one of the most common joint diseases worldwide, and more than 37% people at 60 years of age or older will develop OA. So far, the exact mechanism of OA pathogenesis remains unclear, and the search for an effective disease-modifying approach for OA has been unsuccessful. Epigenetic alterations refer to heritable changes in chromatin organization and biochemical composition that do not involve changes to the DNA sequence itself. Recently, the roles of epigenetic modifications in ageing-related diseases have been widely studied, and numerous OA-involved epigenetic targets have been identified. The disruption of epigenetic information is regarded as a reversible cause of OA. In this review, the most recent studies on pathological processes and epigenetic changes relevant to OA, encompassing different subtypes (knee/hip/spinal, and temporomandibular joint-OA), various epigenetic modulations (DNA methylation, histone modification, non-coding RNAs, and RNA methylation), and therapeutic signaling pathways have been integrated. The current therapies targeting epigenetic machinery, future directions for epigenetic illustrations in OA, and potential epigenetic interventions and epigenetic disease modifying-OA drugs are also further described.
In this research, we examined the regulatory mechanism of small ubiquitin-related modifiers (SUMOs) in the context of acute kidney injury (AKI) induced by renal ischemia-reperfusion injury (IRI). We systematically evaluated the biological function of SUMOylation in the pathological process of IRI by establishing a SUMO1 knockout (SUMO1-/-) mouse model. One-week-old male and female SUMO1-/- mice, along with their wild-type (WT) littermate controls, were employed to establish a 20-min renal ischemia model through unilateral renal artery clamping. Renal tissue specimens were harvested at 48-h postreperfusion, and multidimensional analyses were performed by histopathological assessment, molecular biology testing, and primary cell validation. Compared to the WTcontrols, kidneys of SUMO1-/- mice exhibited more pronounced AKI pathological features post-IRI, including typical injury phenotypes such as increased vacuolization of renal tubular epithelial cells. At the level of molecular mechanisms, the absence of SUMO1 markedly increased the expression of tumor necrosis factor-alpha (TNF-alpha). Notably, the SUMO1-/-group showed increased renal ferritin deposition and increased severity of apoptosis compared with the WT group, suggesting that the lack of SUMOylation exacerbates the process of IRI-induced ferroptosis and programmed cell death. These systematic findings confirm that SUMOylation has an important cytoprotective function during renal IRI, and its mechanism of action may involve multiple pathways such as regulating inflammatory response, maintaining iron metabolic homeostasis, and inhibiting apoptosis.
N6-methyladenosine (m6A) is the predominant internal mRNA modification with dynamic and reversible regulation on almost all aspects of mRNA metabolism, including mRNA stability, splicing, and translation. Three m6A-related proteins 'writers, readers, and erasers' collaborate to regulate the entire process of m6A modification within the organism. The MeRIP-seq technology has expedited research on m6A modifications in plants. Although the distribution of m6A sites varies across plant species, they are predominantly enriched near the stop codon and within the 3' untranslated region (3'UTR) of mRNAs. Beyond its essential roles in plant growth and development, m6A also critically regulates plant responses to biotic and abiotic stresses. This review not only systematically reviews the writers, readers, and erasers associated with m6A modification, but also comprehensively summarizes recent advancements in elucidating the significance of m6A in plant organ development, floral transition, and fruit ripening. Furthermore, we discuss how m6A influences plant-virus relationships and environmental signals. In summary, analyzing m6A modification is expected to show promise in creating crop varieties with enhanced yield, quality, and stress tolerance.
