Epigenomics最新文献

Chromatin forms specific intranuclear structures through physical interactions between specific genomic regions mediated by DNA-binding proteins and/or RNAs. Recent efforts have revealed that these genome organizations and dynamics are involved in various functions of genomic DNA, such as regulation of gene expression, DNA replication, cell division, and epigenetic memory, which are mechanisms underlying cell differentiation and disease development. The methods to detect physically interacting chromatin regions and reconstruct 3D genomic organization can be roughly categorized into four types: (i) microscopic observation of visualized intranuclear structures, (ii and iii) sequencing-based methods including proximity ligation-dependent/independent methods, and (iv) de novo prediction from genomic sequences and other omics data. Here, we review these techniques to detect physical interactions between genomic regions, highlighting their unique advantages and limitations.

Background: Exposure to smoke from biomass combustion is a significant environmental risk factor for chronic obstructive pulmonary disease (COPD). Through epigenome-wide association studies (EWAS), changes in DNA methylation levels associated with pathological conditions can be identified. We aimed to determine the methylation patterns in genes involved in the development of COPD resulting from exposure to biomass-burning smoke (COPD-BBS).

Materials and methods: EWAS was conducted on induced sputum samples from 45 women with stable COPD (COPD-BBS) exposure and 45 women exposed to BBS but without the disease (BBES). Proteins whose genes showed significant differences in methylation and were soluble in the induced sputum supernatant were quantified.

Results: 205 CpG sites were found differentially hypomethylated, and 420 were hypermethylated. The top 50 show genes associated with lung remodeling (FOXP1 p = 0.002, FMOD p = 0.012, EDN1 p = 0.044), the immune system (ALOX5 p = 0.005, IL19 p = 0.047), mucus production (MUC19 p = 0.04), and xenobiotic metabolism (GSTO2 p = 0.02). Of the proteins evaluated, endothelin-1 was decreased in the reference group compared to patients (p = 0.00054).

Conclusions: Gene methylation changes are linked to lung remodeling, immune response, mucus production, and xenobiotic metabolism. Hypermethylation of the cg08450425 site (EDN1) is significant in women with COPD and associated with low endothelin-1 levels.

Neurodegenerative disorders, like Parkinson's and Huntington's disease, have a profound global impact but currently lack effective treatments. Accumulations of misfolded proteins of α-synuclein and huntingtin are a common pathological hallmark in these diseases, respectiveley. Recently, the role of microglia and innate immune memory in modulating neurodegenerative diseases has been studied in more detail. This review explores the mechanisms of microglial activation in Parkinson's and Huntington's, emphasizing innate immune memory, epigenetic reprogramming, and the influence of external triggers such as lipopolysaccharides (LPS) and high-fat diets (HFD). The review also examines therapeutic strategies targeting microglia to mitigate neurodegeneration, including shifting microglial phenotypes from pro-inflammatory to anti-inflammatory states using epigenetic interventions. To support this review, a structured literature search was conducted using PubMed, Scopus, and Web of Science. Keywords included microglia, innate immune memory, epigenetics, neuroinflammation, and disease-specific terms. Future research should focus on improving animal models, investigating environmental stressors, and developing reliable biomarkers to strengthen translational approaches for neuroinflammatory-driven neurodegenerative diseases.

Background: Bladder cancer remains a prevalent malignancy with limited targeted therapies. Circular RNAs have emerged as critical regulators in cancer biology, though their role in ferroptosis remains largely unexplored.

Research design and methods: The expression of circPPP6R1 was examined in BC tissues and cell lines. Functional assays, including Transwell migration, invasion, colony formation, and multiple ferroptosis-related assays, were conducted in vitro and in vivo. Mechanistic studies involved RNA pull-down, RIP, FISH, and mass spectrometry to identify circPPP6R1-interacting proteins.

Results: circPPP6R1 was significantly downregulated in BC and its overexpression inhibited BC cell proliferation, migration, and invasion. Notably, circPPP6R1 enhanced ferroptosis in BC cells. Mechanistically, circPPP6R1 directly bound to UHRF1 and facilitated its ubiquitin-mediated degradation. UHRF1 was found to be highly expressed in BC tissues and correlated with adverse clinicopathological features. Rescue experiments confirmed that the tumor-suppressive effect of circPPP6R1 was mediated through UHRF1-dependent ferroptosis induction.

Conclusions: Our study identifies circPPP6R1 as a novel ferroptosis-promoting circRNA that suppresses BC progression by targeting UHRF1. These findings highlight the circPPP6R1/UHRF1 axis as a potential therapeutic target in bladder cancer.

Adenosine-to-inosine (A-to-I) mRNA editing epigenetically mimics A-to-G mutations. While literatures usually state "inosines are recognized as guanosines," sometimes we also see expressions like "inosines basepair with cytosines." In this article, I stress that the two expressions are not equivalent at all for the following reasons. (1) inosines are recognized as guanosines only when located in mRNAs, not tRNAs; (2) even when being recognized as guanosines, inosines can basepair with cytosine and uracil; (3) when inosine pairs with cytosine, the basepairing efficiency differs from G:C pairing. Therefore, we should be cautious when introducing A-to-I RNA editing. "inosines basepair with cytosines" is an inaccurate or incomplete interpretation and should be corrected as "inosines in mRNAs are recognized as guanosines."

Background: Major depression (MD) is caused by both genetic and environmental factors. Epigenetic mechanisms, particularly DNA methylation (5mC) and hydroxymethylation (5hmC), are thought to mediate gene - environment interactions. However, findings in mouse models remain dispersed.

Objective: This review evaluates the studies on 5mC and 5hmC in mouse models of depression.

Methods: We systematically searched PubMed, Scopus, and Web of Science using terms related to 5mC/5hmC, depression, and mouse, until December 2024. We grouped the articles as candidate, global, cellular, and comprehensive studies and summarized the findings accordingly.

Results: Sixty-eight studies met inclusion criteria. The main findings were environmental models, especially chronic stress paradigms, which were most frequently used to induce depression models. Candidate gene studies focused on Bdnf and Nr3c1, while global and cellular assays revealed both regional and widespread 5mC/5hmC changes. Genome-wide approaches revealed that epigenetic changes are not limited to isolated loci rather affect broad genomic regions involved in neural development and plasticity.

Conclusion: This review provides a comprehensive summary of existing research on epigenetic changes in terms of DNA methylation in mouse models of depression. Broader application of standardized, integrative, and cell-type-specific approaches is needed to fully elucidate the role of epigenetic regulation in the pathology of MD.

Circular RNAs (circRNAs) are a class of covalently closed non-coding RNAs that regulate the progression of multiple cancers. Recent studies have revealed the presence of several post-transcriptional modifications such as N6-methyladenosine (m⁶A), N1-methyladenosine (m¹A), 5-methylcytosine (m⁵C), N4-acetylcytidine (ac⁴C), and N7-methylguanosine (m⁷G) on circRNAs. This review synthesizes the results of articles retrieved through systematic searches of PubMed and Web of science databases, mainly focusing on circRNA modifications in cancers. These modifications affect the biogenesis, metabolism, stability, and function of circRNAs in cancers, highlighting the critical roles of circRNAs modifications in cancers. Moreover, circRNAs crosstalk with epigenetic modifications of mRNA across various cancers, offering new perspectives for cancer therapy. Innovations in detection techniques, such as anti-modifying antibodies and mass spectrometry, have improved the identification and sensitivity of epigenetically modified circRNAs. Emerging technologies including artificial intelligence (AI)-based bioinformatics algorithms will accelerate the development of RNA epigenetic modifications-based precision therapies. Herein, we summarize a range of epigenetically modified circRNAs and their future research directions. We hope to develop clinical protocols that targeting circRNAs modification for the treatment of refractory malignancies.

Aims: To determine if epigenomic and mRNA associations with donor age are present in basal keratinocytes in vitro.

Methods: Whole-genome methylation (EPIC array), RNAseq analysis, and in vitro cell growth assessments were performed on cultured keratinocytes (n = 9, 22-68 years), enriched for cells expressing the stem cell protein markers ITGB1 and EpCAM.

Results: Donor age associated with 1,244 differentially methylated positions (DMPs) (p < 0.01, >20% delta beta) and correlated with estimated ages from the Skin and Blood epigenetic clock (r = 0.83, p = 0.0018). The DMPs correlated with those in an in vivo epidermal dataset (r = 0.71, p < 0.0001). Donor age associated (p < 0.05) with 523 differentially expressed genes (DEGs), but the DEGs only weakly correlated with their changes in an in vivo epidermal dataset (r = 0.24, p < 0.0001). The "cell growth and proliferation" ontology term was significantly enriched in the methylation and expression datasets despite only 13 overlapping annotated genes. Decreased keratinocyte proliferation, increased differentiation and a reduced re-epithelialization ability were observed for an older versus a younger cell strain.

Conclusion: Basal keratinocytes maintain in vivo age-associated epigenomic changes in vitro making them a good model for studying the impact of age-associated epigenomic changes on cellular function and behavior in vitro.

Leukemia is a heterogeneous group of hematological malignancies characterized by uncontrolled proliferation and impaired differentiation of hematopoietic stem and progenitor cells. Epigenetic dysregulation is one of the critical drivers of leukemogenesis, often involving aberrant activity of chromatin-interacting proteins, such as readers, writers, and erasers. Tudor domain-containing proteins, such as SGF29, JMJD2A, 53BP1, Spindlin1, and UHRF1, play pivotal roles in leukemia progression by controlling key processes such as DNA damage response, transcriptional regulation, and RNA metabolism. Several recent efforts have aimed at pharmacologic targeting of the Tudor domain, opening a novel avenue for targeting epigenetic dysregulation. The review explores the structural characteristics of various Tudor domains, their binding preferences for specific histone modifications, and the consequences of these interactions for leukemia. By providing a comprehensive overview of current research, this review underscores the therapeutic potential of Tudor domain-targeting strategies in leukemia and emphasizes the need for further development of epigenetics-based treatment strategies to address resistance and relapse in these malignancies.

Objectives: To validate the potential of the serotonin receptor encoded by 5-hydroxytryptamine receptor 2A (HTR2A) cg15692052 DNA methylation as a diagnostic biomarker for rheumatoid arthritis (RA) and its subtypes.

Methods: MethylTarget^TM targeted region methylation sequencing technology was employed to analyze the DNA methylation levels of HTR2A cg15692052 in RA, health control, ankylosing spondylitis, psoriatic arthritis, gout, systemic lupus erythematosus, dermatomyositis, and primary Sjögren's syndrome patients within the region of chr13:46898190~chr13:46897976. Machine learning algorithms were used to analyze data.

Results: Compared to the HC group, RA patients and four serological subtypes of RA (RF-negative RA, RF/CCP double-positive, RF/CCP double-negative, and CCP-negative RA) exhibited significantly higher levels of HTR2A cg15692052 methylation (p < 0.05). Methylation levels in RA patients and its four serological subtypes were significantly positively correlated with erythrocyte sedimentation rate or C-reactive protein (p < 0.05). HTR2A cg15692052 methylation levels combined with different clinical features can significantly distinguish RA patients with AUCs ranging from 0.672 to 0.757, RF/CCP double-negative patients with AUCs from 0.825 to 0.966, RF/CCP double-positive RA patients with AUCs from 0.714 to 0.846, and RF-negative RA patients with AUCs from 0.928 to 0.932.

Conclusions: The HTR2A cg15692052 DNA methylation level can serve as a diagnostic biomarker for RA and its subtypes.