Epigenomes最新文献_第10页

Dynamics and Malleability of Plant DNA Methylation During Abiotic Stresses. 非生物胁迫下植物DNA甲基化的动态和延展性。

IF 3.5

Epigenomes Pub Date : 2025-08-29 DOI: 10.3390/epigenomes9030031

Niraj Lodhi, Rakesh Srivastava

{"title":"Dynamics and Malleability of Plant DNA Methylation During Abiotic Stresses.","authors":"Niraj Lodhi, Rakesh Srivastava","doi":"10.3390/epigenomes9030031","DOIUrl":"10.3390/epigenomes9030031","url":null,"abstract":"Epigenetic regulation, particularly DNA methylation, plays a crucial role in plant adaptation to environmental stresses by modulating gene expression without altering the underlying DNA sequence. In response to major abiotic stresses such as salinity, drought, heat, cold, and heavy metal toxicity, plants undergo dynamic changes in DNA methylation patterns. These modifications are orchestrated by DNA methyltransferases and demethylases with variations depending on plant species, genetic background, and ontogenic phase. DNA methylation affects the expression of key genes involved in cellular, physiological, and metabolic processes essential for stress tolerance. Furthermore, it contributes to the establishment of stress memory, which can be transmitted across generations, thereby enhancing long-term plant resilience. The interaction of DNA methylation with other epigenetic mechanisms, including histone modifications, small RNAs, and chromatin remodeling, adds layers of regulatory complexity. Recent discoveries concerning N6-methyladenine have opened new avenues for understanding the epigenetic landscape in plant responses to abiotic stress. Overall, this review addresses the central role of DNA methylation in regulating plant stress responses and emphasizes its potential for application in crop improvement through epigenetic and advanced biotechnological approaches.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenetic Mechanisms in Neurofibromatosis Types 1 and 2. 1型和2型神经纤维瘤病的表观遗传机制。

IF 3.5

Epigenomes Pub Date : 2025-08-14 DOI: 10.3390/epigenomes9030030

Christina Stylianides, Gavriel Hadjigavriel, Paschalis Theotokis, Efstratios Vakirlis, Soultana Meditskou, Maria Eleni Manthou, Iasonas Dermitzakis

{"title":"Epigenetic Mechanisms in Neurofibromatosis Types 1 and 2.","authors":"Christina Stylianides, Gavriel Hadjigavriel, Paschalis Theotokis, Efstratios Vakirlis, Soultana Meditskou, Maria Eleni Manthou, Iasonas Dermitzakis","doi":"10.3390/epigenomes9030030","DOIUrl":"10.3390/epigenomes9030030","url":null,"abstract":"Neurocutaneous syndromes, known as phakomatoses, encompass a diverse group of congenital conditions affecting the nervous system and skin, with neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) among the most clinically significant. Both disorders are inherited in an autosomal dominant manner. NF1 presents with café-au-lait macules; cutaneous, subcutaneous, and plexiform neurofibromas; skeletal abnormalities; learning disabilities; and optic pathway gliomas, while NF2 is characterised by bilateral vestibular schwannomas, multiple meningiomas, ependymomas, and peripheral nerve schwannomas. Although germline mutations in the NF1 and NF2 tumour suppressor genes are well established, they do not fully explain the broad clinical variability observed, even among individuals carrying identical mutations. As increasingly recognised in other genetic diseases, epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodelling, and non-coding RNA (ncRNA) regulation, play a critical role in modulating gene expression and influencing disease severity. Despite important findings, the research remains fragmented, and a unified model is lacking. This review organises the current knowledge, emphasising how epigenetic alterations impact disease behaviour and outlining their potential as prognostic biomarkers and therapeutic targets. A deeper understanding of these mechanisms could lead to improved personalised management and the development of targeted epigenetic therapies for individuals with NF1 and NF2.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of Ionizing Radiation in Shaping the Complex Multi-Layered Epigenome. 电离辐射在形成复杂的多层表观基因组中的作用。

IF 3.5

Epigenomes Pub Date : 2025-08-08 DOI: 10.3390/epigenomes9030029

Claudia E Rübe, Mutaz A Abd Al-Razaq, Carola Meier, Markus Hecht, Christian Rübe

{"title":"Role of Ionizing Radiation in Shaping the Complex Multi-Layered Epigenome.","authors":"Claudia E Rübe, Mutaz A Abd Al-Razaq, Carola Meier, Markus Hecht, Christian Rübe","doi":"10.3390/epigenomes9030029","DOIUrl":"10.3390/epigenomes9030029","url":null,"abstract":"The impact of ionizing radiation (IR) with induction of various DNA damage is based not only on genetic but also on epigenetic effects. Epigenetic modifications determine the chromatin structure and DNA accessibility, thereby regulating cellular functions through the expression of individual genes or entire groups of genes. However, the influence of DNA repair processes on the restoration of local chromatin structures and global nuclear architectures is still insufficiently understood. In multicellular organisms, epigenetic mechanisms control diverse cellular functions of specific cell types through precise temporal and spatial regulation of gene expression and silencing. How altered epigenetic mechanisms regulate the pathophysiological function of cells, tissues, and ultimately entire organs following IR exposure remains to be investigated in detail. Radiation-induced epigenetic processes are particularly critical for immature cell populations such as tissue-specific stem and progenitor cells during development and differentiation of organ tissues. Genome-wide patterns of DNA and histone modifications are established cell types-specifically during the development and differentiation of organ tissues but can also be fundamentally altered in adult organism by stress responses, such as radiation-induced DNA damage. Following IR exposure, epigenetic factors are not always fully restored to their original state, resulting in epigenetic dysfunction that causes cells to lose their original identity and function. Moreover, severe radiation-induced DNA damage can induce premature senescence of cells in complex tissues, which ultimately leads to signs of aging and age-related diseases such as cancer. In this work, we provide an overview of the most important epigenetic changes following IR exposure and their pathophysiological significance for the development of acute and chronic radiation reactions.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DNA Methylation Status of Regulatory Regions of Apoptosis-Associated Genes in Dystropy «Huntington's Disease-Non-Small Cell Lung Cancer». 营养不良«亨廷顿病-非小细胞肺癌»中凋亡相关基因调控区域的DNA甲基化状态。

IF 3.5

Epigenomes Pub Date : 2025-08-07 DOI: 10.3390/epigenomes9030028

Nadezhda P Babushkina, Elena Yu Bragina, Densema E Gomboeva, Iuliia A Koroleva, Sergey N Illarioshkin, Sergey A Klyushnikov, Nataliya Yu Abramycheva, Maria A Nikitina, Valentina M Alifirova, Nikolai V Litviakov, Marina K Ibragimova, Matvey M Tsyganov, Irina A Tsydenova, Aleksei A Zarubin, Irina A Goncharova, Maria V Golubenko, Ramil R Salakhov, Aleksei A Sleptcov, Aksana N Kucher, Maria S Nazarenko, Valery P Puzyrev

{"title":"DNA Methylation Status of Regulatory Regions of Apoptosis-Associated Genes in Dystropy «Huntington's Disease-Non-Small Cell Lung Cancer».","authors":"Nadezhda P Babushkina, Elena Yu Bragina, Densema E Gomboeva, Iuliia A Koroleva, Sergey N Illarioshkin, Sergey A Klyushnikov, Nataliya Yu Abramycheva, Maria A Nikitina, Valentina M Alifirova, Nikolai V Litviakov, Marina K Ibragimova, Matvey M Tsyganov, Irina A Tsydenova, Aleksei A Zarubin, Irina A Goncharova, Maria V Golubenko, Ramil R Salakhov, Aleksei A Sleptcov, Aksana N Kucher, Maria S Nazarenko, Valery P Puzyrev","doi":"10.3390/epigenomes9030028","DOIUrl":"10.3390/epigenomes9030028","url":null,"abstract":"Background. Studies of comorbid (syntropic) and inversely comorbid (rarely occurring together, i.e., dystropic) diseases have focused on the search for molecular causes of this phenomenon. Materials. We investigated DNA methylation levels in regulatory regions of 23 apoptosis-associated genes as candidate loci associated with the \"cancer-neurodegeneration\" dystropy in patients with Huntington's disease (HD) and patients with non-small cell lung cancer (LC). Results. Statistically significant differences in methylation levels between the HD and LC groups were found for 41 CpG sites in 16 genes. The results show that five genes (SETDB1, TWIST1, HDAC1, SP1, and GRIA2) are probably involved in the phenomenon of inverse comorbidity of these diseases. For these genes, the methylation levels of the studied CpG sites were altered in opposite directions in the two groups of patients, compared to the control group. Conclusions. For the SP1 gene, the above hypothesis is supported by our analysis of open-access data on gene expression in patients with the aforementioned diagnoses and fits a probable mechanism of the \"HD-LC\" dystropy.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12371915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting the Kynureninase-HDAC6-Complement Axis as a Novel Therapeutic Strategy in Glioblastoma. 靶向犬尿酸酶- hdac6 -补体轴治疗胶质母细胞瘤的新策略

IF 3.5

Epigenomes Pub Date : 2025-07-28 DOI: 10.3390/epigenomes9030027

Arif Ul Hasan, Sachiko Sato, Mami Obara, Yukiko Kondo, Eiichi Taira

{"title":"Targeting the Kynureninase-HDAC6-Complement Axis as a Novel Therapeutic Strategy in Glioblastoma.","authors":"Arif Ul Hasan, Sachiko Sato, Mami Obara, Yukiko Kondo, Eiichi Taira","doi":"10.3390/epigenomes9030027","DOIUrl":"10.3390/epigenomes9030027","url":null,"abstract":"Background/Objectives: Glioblastoma (GBM) is an aggressive brain tumor known for its profound heterogeneity and treatment resistance. Dysregulated complement signaling and epigenetic alterations have been implicated in GBM progression. This study identifies kynureninase (KYNU), a key enzyme in the kynurenine pathway, as a novel regulator of complement components and investigates its interaction with histone deacetylase 6 (HDAC6) in the context of therapeutic targeting. Methods: KYNU expression, and its association with complement signaling in GBM, were analyzed using publicly available datasets (TCGA, GTEx, HPA). Pathway enrichment was performed via LinkedOmics. In vitro studies in GBM cell lines (U87, U251, T98G) assessed the effects of KYNU silencing and treatment with an HDAC6 inhibitor (tubastatin) and a BET inhibitor (apabetalone) on gene expression and cell viability. Results: Bioinformatic analyses revealed significant overexpression of KYNU in GBM tissues compared to normal brain tissue. KYNU expression was positively associated with genes involved in complement and coagulation cascades. In vitro experiments demonstrated that KYNU silencing reduced the expression of C3, C3AR1, and C5AR1 and suppressed GBM cell viability. Treatment with tubastatin, while reducing viability, paradoxically upregulated complement genes, suggesting potential limitations in therapeutic efficacy. However, this effect was mitigated by KYNU knockdown. Combined treatment with apabetalone and tubastatin effectively suppressed KYNU expression and enhanced cytotoxicity, particularly in cells with high complement expression. Conclusions: Our findings establish the KYNU-HDAC6-complement axis as a critical regulatory pathway in GBM. Targeting KYNU-mediated complement activation through combined epigenetic approaches-such as HDAC6 and BET inhibition-represents a promising strategy to overcome complement-driven resistance in GBM therapy.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenomic Interactions Between Chronic Pain and Recurrent Pressure Injuries After Spinal Cord Injury. 脊髓损伤后慢性疼痛和复发性压力损伤之间的表观基因组相互作用。

IF 4.1

Epigenomes Pub Date : 2025-07-23 DOI: 10.3390/epigenomes9030026

Letitia Y Graves, Melissa R Alcorn, E Ricky Chan, Katelyn Schwartz, M Kristi Henzel, Marinella Galea, Anna M Toth, Christine M Olney, Kath M Bogie

{"title":"Epigenomic Interactions Between Chronic Pain and Recurrent Pressure Injuries After Spinal Cord Injury.","authors":"Letitia Y Graves, Melissa R Alcorn, E Ricky Chan, Katelyn Schwartz, M Kristi Henzel, Marinella Galea, Anna M Toth, Christine M Olney, Kath M Bogie","doi":"10.3390/epigenomes9030026","DOIUrl":"10.3390/epigenomes9030026","url":null,"abstract":"Background/objectives: This study investigated variations in DNA methylation patterns associated with chronic pain and propensity for recurrent pressure injuries (PrI) in persons with spinal cord injury (SCI).Methods: Whole blood was collected from 81 individuals with SCI. DNA methylation was quantified using Illumina genome-wide arrays (EPIC and EPICv2). Comprehensive clinical profiles collected included secondary health complications, in particular current PrI and chronic pain. Relationships between recurrent PrI and chronic pain and whether the co-occurrence of both traits was mediated by changes in DNA methylation were investigated using R packages limma, DMRcate and mCSEA.Results: Three differentially methylated positions (DMPs) (cg09867095, cg26559694, cg24890286) and one region in the micro-imprinted locus for BLCAP/NNAT are associated with chronic pain in persons with SCI. The study cohort was stratified by PrI status to identify any sites associated with chronic pain and while the same three sites and region were replicated in the group with no recurrent PrI, two novel, hypermethylated (cg21756558, cg26217441) sites and one region in the protein-coding gene FDFT1 were identified in the group with recurrent PrI. Gene enrichment and genes associated with specific promoters using MetaScape identified several shared disorders and ontology terms between independent phenotypes of pain and recurrent PrI and interactive sub-groups.Conclusions: DMR analysis using mCSEA identified several shared genes, promoter-associated regions and CGI associated with overall pain and PrI history, as well as sub-groups based on recurrent PrI history. These findings suggest that a much larger gene regulatory network is associated with each phenotype. These findings require further validation.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring Epigenetic Ageing Using Direct Methylome Sequencing. 使用直接甲基组测序探索表观遗传衰老。

IF 3.5

Epigenomes Pub Date : 2025-07-14 DOI: 10.3390/epigenomes9030025

Elena-Cristina Găitănaru, Roua Gabriela Popescu, Andreea-Angelica Stroe, Sergiu Emil Georgescu, George Cătălin Marinescu

引用次数: 0

Trends in DNA Methylation over Time Between Parous and Nulliparous Young Women. 生育和未生育年轻女性DNA甲基化随时间的变化趋势。

IF 3.5

Epigenomes Pub Date : 2025-07-10 DOI: 10.3390/epigenomes9030024

Su Chen, John W Holloway, Wilfried Karmaus, Hongmei Zhang, S Hasan Arshad, Susan Ewart

{"title":"Trends in DNA Methylation over Time Between Parous and Nulliparous Young Women.","authors":"Su Chen, John W Holloway, Wilfried Karmaus, Hongmei Zhang, S Hasan Arshad, Susan Ewart","doi":"10.3390/epigenomes9030024","DOIUrl":"10.3390/epigenomes9030024","url":null,"abstract":"Background/objectives: The experience of pregnancy and parturition has been associated with long-term health effects in mothers, imparting protective effects against some diseases while the risk of other diseases is increased. The mechanisms that drive these altered disease risks are unknown. This study examined DNA methylation (DNAm) changes from pre-pregnancy to several years after giving birth in parous women compared to nulliparous controls over the same time interval.Methods: Using 180 parous-associated CpGs, three analyses were carried out to test DNAm changes from pre-pregnancy at age 18 years to gestation; from gestation to post-pregnancy at age 26 years in parous women; and from 18 to 26 years in nulliparous women using linear mixed models with repeated measures.Results: The directions of DNAm changes were the same between the parous and nulliparous groups. Most CpG dinucleotides (67%, 121 of 180) had a decreasing trend while a small number (7%, 13 of 180) had an increasing trend. Of the CpGs showing increasing or decreasing DNAm, approximately half had DNAm change to a smaller extent in parous women and the other half changed more in parous women than nulliparous controls. 9% (17 of 180) changed significantly in nulliparous women only, leading to a significant difference in DNAm levels in parous women at the post-pregnancy 26 years time point.Conclusions: Pregnancy and parturition may accelerate methylation changes in some CpGs, but slow down or halt methylation changes over time in other CpGs.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Fundamental Role of Nutrients for Metabolic Balance and Epigenome Integrity Maintenance. 营养物质在代谢平衡和维持表观基因组完整性中的基本作用。

IF 3.5

Epigenomes Pub Date : 2025-07-09 DOI: 10.3390/epigenomes9030023

Ana Paula de Souza, Vitor Marinho, Marcelo Rocha Marques

{"title":"The Fundamental Role of Nutrients for Metabolic Balance and Epigenome Integrity Maintenance.","authors":"Ana Paula de Souza, Vitor Marinho, Marcelo Rocha Marques","doi":"10.3390/epigenomes9030023","DOIUrl":"10.3390/epigenomes9030023","url":null,"abstract":"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.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Methylation of the Glucocorticoid Receptor Gene in Children with Somatic Symptom Disorder: A Case-Control Study. 躯体症状障碍儿童糖皮质激素受体基因甲基化：一项病例对照研究

IF 2.5

Epigenomes Pub Date : 2025-06-13 DOI: 10.3390/epigenomes9020022

Kyoko Hatta, Masato Kantake, Kyoko Tanaka, Hirofumi Nakaoka, Toshiaki Shimizu, Hiromichi Shoji

{"title":"Methylation of the Glucocorticoid Receptor Gene in Children with Somatic Symptom Disorder: A Case-Control Study.","authors":"Kyoko Hatta, Masato Kantake, Kyoko Tanaka, Hirofumi Nakaoka, Toshiaki Shimizu, Hiromichi Shoji","doi":"10.3390/epigenomes9020022","DOIUrl":"10.3390/epigenomes9020022","url":null,"abstract":"Background: Somatic symptom disorder (SSD) in children may be influenced by stress reactivity and psychosocial factors. The glucocorticoid receptor (GR), encoded by NR3C1, is a key mediator of stress responses. However, the relationship between NR3C1 methylation and SSD remains unclear. Methods: We analyzed NR3C1 exon 1F methylation in cell-free DNA from saliva in 34 children with SSD and 29 age- and sex-matched controls using bisulfite amplicon sequencing. Psychological assessments included the Beck Depression Inventory-II (BDI-II) and KINDL questionnaires to evaluate associations with methylation patterns. Results: Methylation levels showed age-related differences. In children under 13, CpG sites displayed mixed methylation, and specific sites correlated with KINDL and BDI-II scores. KINDL physical and total well-being scores negatively correlated with CpG30 and positively with CpG35; BDI-II scores negatively correlated with CpG32 and CpG35. In children aged 13 or older, CpG sites showed uniformly high methylation with no correlation to psychological measures. The SSD group showed significantly higher average methylation across the exon 1F region than controls in the older age group. These children also had more cases of orthostatic dysregulation and longer illness duration. Conclusions: This study suggests age-dependent epigenetic regulation of NR3C1 in SSD. While younger children showed CpG-specific correlations with psychological symptoms, older children demonstrated uniformly high methylation and potentially reduced gene expression, potentially reflecting cumulative stress, autonomic dysfunction, and internalizing disorders such as anxiety and depression.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12192148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0