Epigenomes最新文献

{"title":"Epigenome-Wide and Methylation Risk Score Analysis of Body Mass Index Among People with HIV.","authors":"Nanzha Abi, Alexandra Young, Pradeep Tiwari, Junyu Chen, Chang Liu, Qin Hui, Kaku So-Armah, Matthew S Freiberg, Amy C Justice, Ke Xu, Marta Gwinn, Vincent C Marconi, Yan V Sun","doi":"10.3390/epigenomes8040046","DOIUrl":"10.3390/epigenomes8040046","url":null,"abstract":"<p><p><b>Background/Objectives:</b> People with HIV (PWH) on antiretroviral therapy (ART) often gain weight, which increases their risk of type 2 diabetes and cardiovascular disease. The role of DNA methylation (DNAm) markers in obesity among PWH is understudied. This research explores the relationship between body mass index (BMI) and epigenetic patterns to better understand and manage obesity-related risks in PWH. <b>Methods:</b> We conducted an epigenome-wide association study (EWAS) on 892 African American male PWH from the Veterans Aging Cohort Study, examining BMI associations with DNAm using linear mixed models, adjusting for covariates, including soluble CD14. We compared our results with BMI-associated DNAm markers from non-HIV individuals and developed a methylation risk score (MRS) for BMI using machine learning and a cross-validation approach. <b>Results:</b> We identified four epigenome-wide significant CpG sites, including one in the <i>RAP1B</i> gene, indicating shared and unique BMI-related epigenetic markers between PWH and non-HIV individuals. The constructed BMI MRS explained approximately 19% of the BMI variance in PWH. <b>Conclusions:</b> DNAm markers and MRS are significantly linked to BMI in PWH, suggesting shared and distinct molecular mechanisms with non-HIV populations. These insights could lead to targeted interventions to reduce cardiometabolic disease risks in PWH under ART.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11675887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900679","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}

{"title":"DNA Imprinting and Differentially Expressed Genes in <i>Longissimus thoracis</i> Muscle of <i>Bos indicus</i> Submitted to Early Weaning Management.","authors":"Gustavo Tinoco, Gustavo Russo, Rogério Curi, Marcelo Vicari, Paloma Melo, Isabella Souza, Juliana Torrecilhas, Philipe Moriel, Welder Baldassini, Luis Chardulo, Otávio Neto, Guilherme Pereira","doi":"10.3390/epigenomes8040045","DOIUrl":"10.3390/epigenomes8040045","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Early weaning management followed by energy supplementation can lead to metabolic alterations in the calf that exert long-term effects on the animal's health and performance. It is believed that the main molecular basis underlying these metabolic adaptations are epigenetic mechanisms that regulate, activate, or silence genes at different stages of development and/or in response to different environmental stimuli. However, little is known about postnatal metabolic programming in <i>Bos indicus</i>. Therefore, this study aimed to compare the DNA methylation profile of Nellore animals submitted to conventional and early weaning and to correlate the findings with genes differentially expressed in the <i>Longissimus thoracis</i> skeletal muscle of <i>Bos indicus</i> cattle. <b>Methods:</b> For this, we used Reduced Representation Bisulfite Sequencing (RRBS) and RNA-Sequencing techniques to prospect differentially methylated genes (DMGs). <b>Results:</b> A total of 481 differentially methylated regions were identified, with 52% (250) being hypermethylated and 48% (231) hypomethylated. Functional enrichment analysis of 53 differentially methylated and differentially expressed genes was performed. The main enriched terms and pathways were associated with 3'-5'-cyclic adenosine monophosphate (<i>cAMP</i>) signaling, which presents the upregulated adenylate cyclase 3 (<i>ADCY3</i>) gene and significatively hypomethylated in the promoter region. Alterations in cAMP signaling are involved in numerous processes, many of them related to lipid metabolism. The relative differential expression of key genes of this pathway demonstrates the relationship between cAMP signaling and de novo lipogenesis. <b>Conclusions</b>: These findings suggest an important role of postnatal metabolic programming through DNA methylation mechanisms in determining fat deposition in beef.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11675247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900675","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}

{"title":"Age-Dependent DNA Methylation Variability on the X-Chromosome in Male and Female Twins.","authors":"Qihua Tan, Hikmat Alo, Marianne Nygaard, Mette Sørensen, Alisa Saleh, Jonas Mengel-From, Kaare Christensen","doi":"10.3390/epigenomes8040043","DOIUrl":"10.3390/epigenomes8040043","url":null,"abstract":"<p><p>We aimed to explore the age-dependent epigenetic variability on the X-chromosome with consideration of X-chromosome inactivation by applying a sex-stratified regression analysis to DNA methylation array data on X-linked CpGs in aging identical twins. We found 13 X-linked CpGs showing age-related significant increase in variability in males (FDR < 0.05) but none in females. In females, we found a significantly higher proportion of CpGs showing increased variability with age among nominally significant (<i>p</i> < 0.05) CpGs under inactivation, but not among CpGs escaping inactivation. Survival analysis showed a slight trend of correlation by directional change in the variable CpGs with mortality in males. Compared with females, the male X-chromosome can be more vulnerable to epigenetic instability during aging.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711811","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}

{"title":"Histone Modification Pathways Suppressing Cryptic Transcription.","authors":"Hong-Yeoul Ryu","doi":"10.3390/epigenomes8040042","DOIUrl":"10.3390/epigenomes8040042","url":null,"abstract":"<p><p>Cryptic transcription refers to the unintended expression of non-canonical sites within the genome, producing aberrant RNA and proteins that may disrupt cellular functions. In this opinion piece, I will explore the role of histone modifications in modulating cryptic transcription and its implications for gene expression and cellular integrity, particularly with a focus on H3K36 and H3K4 methylation marks. H3K36 tri-methylation plays a crucial role in maintaining chromatin integrity by facilitating the recruitment of the Rpd3S histone deacetylase (HDAC) complex, which helps restore closed chromatin states following transcription and prevents cryptic initiation within gene bodies. In parallel, crosstalk between H3K4 di-methylation and histone ubiquitylation and sumoylation is critical for recruiting the Set3 HDAC complex, which maintains low histone acetylation levels in gene bodies and further suppresses cryptic transcription. Therefore, by elucidating these regulatory mechanisms, this opinion highlights the intricate interplay of histone modifications in preserving transcriptional fidelity and suggests potential pathways for future research to develop novel therapies for age-related disorders and other diseases associated with dysregulated gene expression.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711784","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}

{"title":"Epigenetic Landscape of DNA Methylation in Pancreatic Ductal Adenocarcinoma.","authors":"Peiyi Liu, Juliette Jacques, Chang-Il Hwang","doi":"10.3390/epigenomes8040041","DOIUrl":"10.3390/epigenomes8040041","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, characterized by its aggressive progression and dismal prognosis. Advances in epigenetic profiling, specifically DNA methylation analysis, have significantly deepened our understanding of PDAC pathogenesis. This review synthesizes findings from recent genome-wide DNA methylation studies, which have delineated a complex DNA methylation landscape differentiating between normal and cancerous pancreatic tissues, as well as across various stages and molecular subtypes of PDAC. These studies identified specific differentially methylated regions (DMRs) that not only enhance our grasp of the epigenetic drivers of PDAC but also offer potential biomarkers for early diagnosis and prognosis, enabling the customization of therapeutic approaches. The review further explores how DNA methylation profiling could facilitate the development of subtype-tailored therapies, potentially improving treatment outcomes based on precise molecular characterizations. Overall, leveraging DNA methylation alterations as functional biomarkers holds promise for advancing our understanding of disease progression and refining PDAC management strategies, which could lead to improved patient outcomes and a deeper comprehension of the disease's underlying biological mechanisms.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711768","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}

{"title":"Transcription Factors Are Involved in Wizened Bud Occurrence During the Growing Season in the <i>Pyrus pyrifolia</i> Cultivar 'Sucui 1'.","authors":"Hui Li, Jialiang Kan, Chunxiao Liu, Qingsong Yang, Jing Lin, Xiaogang Li","doi":"10.3390/epigenomes8040040","DOIUrl":"10.3390/epigenomes8040040","url":null,"abstract":"<p><strong>Background: </strong>Flowers are important plant organs, and their development is correlated with yield in woody fruit trees. For <i>Pyrus pyrifolia</i> cultivar 'Sucui 1', the research on how DNA methylation accurately regulates the expression of TFs and affects the specific regulatory mechanism of flower bud wizening will help reduce wizened buds.</p><p><strong>Methods: </strong>Here, the DNA methylomes and transcriptomes of two types of flower buds from the <i>Pyrus pyrifolia</i> cultivar 'Sucui 1' were compared.</p><p><strong>Results: </strong>320 differentially expressed transcription factors (TFs), in 43 families, were obtained from the wizened bud transcriptome versus the normal bud transcriptome. Most were members of the AP2/ERF, bHLH, C2H2, CO-like, MADS, MYB, and WRKY families, which are involved in flower development. As a whole, the methylation level of TFs in the 'Sucui 1' genome increased once flower bud wizening occurred. A cytosine methylation analysis revealed that the methylation levels of the same gene regions in TFs from two kinds of buds were similar. However, differentially methylated regions were found in gene promoter sequences. The combined whole-genome bisulfite sequencing and RNA-Seq analyses revealed 162 TF genes (including 164 differentially methylated regions) with both differential expression and methylation differences between the two flower bud types. Among them, 126 were classified as ^mCHH-type methylation genes. Furthermore, the transcriptional down regulation of <i>PpbHLH40</i>, <i>PpERF4</i>, <i>PpERF061</i>, <i>PpLHW</i>, <i>PpMADS6</i>, <i>PpZF-HD11</i>, and <i>PpZFP90</i> was accompanied by increased DNA methylation. However, <i>PpbHLH130</i>, <i>PpERF011</i>, and <i>PpMYB308</i> displayed the opposite trend. The expression changes for these TFs were negatively correlated with their methylation states.</p><p><strong>Conclusions: </strong>Overall, our results offer initial experimental evidence of a correlation between DNA methylation and TF transcription in <i>P. pyrifolia</i> in response to bud wizening. This enriched our understanding of epigenetic modulations in woody trees during flower development.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711793","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}

{"title":"Associations between Circulating Biomarkers of One-Carbon Metabolism and Mitochondrial D-Loop Region Methylation Levels.","authors":"Andrea Stoccoro, Martina Lari, Lucia Migliore, Fabio Coppedè","doi":"10.3390/epigenomes8040038","DOIUrl":"https://doi.org/10.3390/epigenomes8040038","url":null,"abstract":"<p><strong>Background/objectives: </strong>One-carbon metabolism is a critical pathway for epigenetic mechanisms. Circulating biomarkers of one-carbon metabolism have been associated with changes in nuclear DNA methylation levels in individuals affected by age-related diseases. More and more studies are showing that even mitochondrial DNA (mtDNA) could be methylated. In particular, methylation of the mitochondrial displacement (D-loop) region modulates the gene expression and replication of mtDNA and, when altered, can contribute to the development of human illnesses. However, no study until now has demonstrated an association between circulating biomarkers of one-carbon metabolism and D-loop methylation levels.</p><p><strong>Methods: </strong>In the study presented herein, we searched for associations between circulating one-carbon metabolism biomarkers, including folate, homocysteine, and vitamin B12, and the methylation levels of the D-loop region in DNA obtained from the peripheral blood of 94 elderly voluntary subjects.</p><p><strong>Results: </strong>We observed a positive correlation between D-loop methylation and vitamin B12 (r = 0.21; <i>p</i> = 0.03), while no significant correlation was observed with folate (r = 0.02; <i>p</i> = 0.80) or homocysteine levels (r = 0.02; <i>p</i> = 0.82). Moreover, D-loop methylation was increased in individuals with high vitamin B12 levels compared to those with normal vitamin B12 levels (<i>p</i> = 0.04).</p><p><strong>Conclusions: </strong>This is the first study suggesting an association between vitamin B12 circulating levels and mtDNA methylation in human subjects. Given the potential implications of altered one-carbon metabolism and mitochondrial epigenetics in human diseases, a deeper understanding of their interaction could inspire novel interventions with beneficial effects for human health.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513536","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}

{"title":"PHF8/KDM7B: A Versatile Histone Demethylase and Epigenetic Modifier in Nervous System Disease and Cancers.","authors":"Tingyu Fan, Jianlian Xie, Guo Huang, Lili Li, Xi Zeng, Qian Tao","doi":"10.3390/epigenomes8030036","DOIUrl":"10.3390/epigenomes8030036","url":null,"abstract":"<p><p>Many human diseases, such as malignant tumors and neurological diseases, have a complex pathophysiological etiology, often accompanied by aberrant epigenetic changes including various histone modifications. Plant homologous domain finger protein 8 (PHF8), also known as lysine-specific demethylase 7B (KDM7B), is a critical histone lysine demethylase (KDM) playing an important role in epigenetic modification. Characterized by the zinc finger plant homology domain (PHD) and the Jumonji C (JmjC) domain, PHF8 preferentially binds to H3K4me3 and erases repressive methyl marks, including H3K9me1/2, H3K27me1, and H4K20me1. PHF8 is indispensable for developmental processes and the loss of PHF8 enzyme activity is linked to neurodevelopmental disorders. Moreover, increasing evidence shows that PHF8 is highly expressed in multiple tumors as an oncogenic factor. These findings indicate that studying the role of PHF8 will facilitate the development of novel therapeutic agents by the manipulation of PHF8 demethylation activity. Herein, we summarize the current knowledge of PHF8 about its structure and demethylation activity and its involvement in development and human diseases, with an emphasis on nervous system disorders and cancer. This review will update our understanding of PHF8 and promote the clinical transformation of its predictive and therapeutic value.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142301725","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}

{"title":"Decoding the Epigenetics of Infertility: Mechanisms, Environmental Influences, and Therapeutic Strategies.","authors":"Lara Saftić Martinović, Tea Mladenić, Dora Lovrić, Saša Ostojić, Sanja Dević Pavlić","doi":"10.3390/epigenomes8030034","DOIUrl":"10.3390/epigenomes8030034","url":null,"abstract":"<p><p>Infertility is a complex condition caused by a combination of genetic, environmental, and lifestyle factors. Recent advances in epigenetics have highlighted the importance of epigenetic changes in fertility regulation. This review aims to provide a comprehensive overview of the epigenetic mechanisms involved in infertility, with a focus on DNA methylation, histone modification, and non-coding RNAs. We investigate the specific epigenetic events that occur during gametogenesis, with a focus on spermatogenesis and oogenesis as distinct processes. Furthermore, we investigate how environmental factors such as diet, stress, and toxin exposure can influence these epigenetic changes, potentially leading to infertility. The second part of the review explores epigenetic changes as therapeutic targets for infertility. Emerging therapies that modulate epigenetic marks present promising opportunities for fertility restoration, particularly in spermatogenesis. By summarizing current research findings, this review emphasizes the importance of understanding epigenetic contributions to infertility. Our discussion aims to lay the groundwork for future research directions and clinical applications in reproductive health.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142301724","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}

{"title":"α-Crystalline Domains and Intrinsically Disordered Regions Can Work in Parallel to Induce Accumulation of MBD6 at Chromocenters in <i>Arabidopsis thaliana</i>.","authors":"Brandon A Boone, Cristy P Mendoza, Noah J Behrendt, Steven E Jacobsen","doi":"10.3390/epigenomes8030033","DOIUrl":"10.3390/epigenomes8030033","url":null,"abstract":"<p><p>Proteins are localized and concentrated at cellular and genomic locations for specific and efficient functions. Efforts to understand protein accumulation in eukaryotic organisms have primarily focused on multivalent interactions between intrinsically disordered regions (IDRs) as mediators of protein condensation. We previously showed that α-crystalline domain (ACD) proteins 15 (ACD15) and 21 (ACD21) were required for multimerization and the accumulation of gene-silencing methyl-CpG-binding domain protein 6 (MBD6) at chromocenters in <i>Arabidopsis thaliana</i>. Here, we demonstrate that ACDs and IDRs can act as parallel mechanisms, facilitating higher-order MBD6 assemblies. Using human IDRs known to be important for protein accumulation, we replicated and enhanced the accumulation of MBD6 at chromocenters. In addition, IDRs fused to MBD6 could substitute for ACD function and partially reconstitute the MBD6 gene-silencing function. However, the accumulation of MBD6 by IDRs still required ACD15 and ACD21 for full effect. These results establish that ACD-mediated protein accumulation is a mechanism that can function similarly to and together with IDR-mediated mechanisms.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142301727","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}