Frontiers in epigenetics and epigenomics最新文献_第5页

Quantification of tumour-infiltrating immune cells through deconvolution of DNA methylation data in Ewing sarcomas. 通过DNA甲基化数据反褶积来量化尤因肉瘤中肿瘤浸润免疫细胞。

Frontiers in epigenetics and epigenomics Pub Date : 2024-09-04 eCollection Date: 2024-01-01 DOI: 10.3389/freae.2024.1427399

Sara Patrizi, Silvia Vallese, Lucia Pedace, Claudia Nardini, Alessandra Stracuzzi, Sabina Barresi, Isabella Giovannoni, Luana Abballe, Celeste Antonacci, Ida Russo, Angela Di Giannatale, Rita Alaggio, Franco Locatelli, Giuseppe Maria Milano, Evelina Miele

{"title":"Quantification of tumour-infiltrating immune cells through deconvolution of DNA methylation data in Ewing sarcomas.","authors":"Sara Patrizi, Silvia Vallese, Lucia Pedace, Claudia Nardini, Alessandra Stracuzzi, Sabina Barresi, Isabella Giovannoni, Luana Abballe, Celeste Antonacci, Ida Russo, Angela Di Giannatale, Rita Alaggio, Franco Locatelli, Giuseppe Maria Milano, Evelina Miele","doi":"10.3389/freae.2024.1427399","DOIUrl":"10.3389/freae.2024.1427399","url":null,"abstract":"Ewing Sarcomas (EWS, OMIM#612219) presents a major challenge in pediatric oncology due to its aggressive nature and poor prognosis, particularly in metastatic cases. Genetic fusions involving the EWSR1 gene and ETS family transcription factors are common in EWS, though other rarer fusions have also been identified. Current standard techniques like immunohistochemistry have failed to fully characterize the immune tumor microenvironment of EWS, hindering insights into tumor development and treatment strategies. Recent efforts apply gene expression datasets to quantify tumor-infiltrating immune cells in EWS. Similar deconvolution techniques can be also applied to DNA methylation (DNAm) arrays, which are much more stable compared to RNA-based methods. This study aims to characterize immune cell infiltration in EWS using DNAm array data. We collected 32 EWS samples from 32 consecutive patients referred to Bambino Gesù Children's Hospital. DNAm analysis was performed by EPIC arrays; data loading, normalization, deconvolution and survival analysis were then performed in R programming environment. We observed a higher content of dendritic cells and longer overall survival in samples with EWSR1::FLI1 translocation compared to samples with rarer fusions. Moreover, T-memory lymphocytes and monocytes emerged as a significant predictor of overall survival. This study underscores the potential of DNAm arrays in providing robust insights into EWS immune profiles, offering a promising avenue for future research. Further investigations with larger cohorts are warranted to validate these findings and explore additional immune cell types influencing EWS outcomes.","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"2 ","pages":"1427399"},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121617","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

Transgenerational epigenetic inheritance: a critical perspective. 跨代表观遗传：一个批判的视角。

Frontiers in epigenetics and epigenomics Pub Date : 2024-08-30 DOI: 10.3389/freae.2024.1434253

Adrian Bird

引用次数: 0

Histone H2A variants play a key role at DNA double-strand breaks during repair pathway choice. 组蛋白H2A变异在DNA双链断裂修复途径选择中起关键作用。

Frontiers in epigenetics and epigenomics Pub Date : 2024-08-22 eCollection Date: 2024-01-01 DOI: 10.3389/freae.2024.1445765

Emile Clerf, Maxime Galloy, Amélie Fradet-Turcotte, Jacques Côté

{"title":"Histone H2A variants play a key role at DNA double-strand breaks during repair pathway choice.","authors":"Emile Clerf, Maxime Galloy, Amélie Fradet-Turcotte, Jacques Côté","doi":"10.3389/freae.2024.1445765","DOIUrl":"10.3389/freae.2024.1445765","url":null,"abstract":"Histone post-translational modifications and variants play crucial roles in the adaptability of chromatin structure, facilitating rapid responses necessary for biological processes such as transcription, replication, and DNA damage signaling. Notably, DNA double-strand break (DSB) signaling heavily relies on these histone modifications, with signal amplification and the recruitment of specific DNA repair factors being dictated by them. Among the histones, H2A and its variants are central to this response, with phosphorylation of the variant H2A.X being the initial and most characteristic histone mark deposit upon DNA damage detection. Additional post-translational modifications of H2A and its variants contribute to the selective recruitment of DNA repair factors and influence the choice of DNA repair pathways. This review provides a summary of current knowledge regarding the roles of histone H2A post-translational modifications and variants in DSB signaling and repair, with a particular emphasis on modifications and variants that impact the choice of repair pathways. Additionally, the involvement of histone chaperones, chromatin modifiers, and remodelers in these processes is discussed.","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"2 ","pages":"1445765"},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121577","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

Transcription factor network dynamics during the commitment to oncogene-induced senescence 转录因子网络在癌基因诱导的衰老过程中的动态变化

Frontiers in epigenetics and epigenomics Pub Date : 2024-07-15 DOI: 10.3389/freae.2024.1423454

Themistoklis Vasilopoulos, R. Martínez-Zamudio

{"title":"Transcription factor network dynamics during the commitment to oncogene-induced senescence","authors":"Themistoklis Vasilopoulos, R. Martínez-Zamudio","doi":"10.3389/freae.2024.1423454","DOIUrl":"https://doi.org/10.3389/freae.2024.1423454","url":null,"abstract":"Aberrant oncogenic signaling causes cells to transition into oncogene-induced senescence (OIS) to limit uncontrolled proliferation. Despite being a potent tumor suppressor mechanism, OIS is an unstable cell state susceptible to reprogramming that can promote tumorigenesis. Therefore, elucidating the underlying gene regulatory mechanisms that commit cells to OIS is critical to identifying actionable targets to modulate the senescence state. We previously showed that timely execution of the OIS program is governed by hierarchical transcription factor (TF) networks. However, the gene regulatory mechanisms that prime cells to commit to the OIS fate early upon oncogene hyperactivation are currently not known. Here, we leveraged our time-resolved multi-omic profiling approach to generate TF networks during the first 24 h of oncogenic HRASG12V activation. Using this approach, we demonstrate that the commitment to OIS requires the rearrangement of the TF network on a pre-established epigenomic landscape, priming the cells for the substantial chromatin remodeling that underpins the transition to OIS. Our results provide a detailed map of the chromatin landscape before cells transition to OIS thus offering a platform for manipulation of senescence outcomes of potentially therapeutic value.","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"15 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141648232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PIF transcription factors-versatile plant epigenome landscapers PIF 转录因子--多才多艺的植物表观基因组景观设计师

Frontiers in epigenetics and epigenomics Pub Date : 2024-05-16 DOI: 10.3389/freae.2024.1404958

Moonia Ammari, Kashif Maseh, Mark Zander

{"title":"PIF transcription factors-versatile plant epigenome landscapers","authors":"Moonia Ammari, Kashif Maseh, Mark Zander","doi":"10.3389/freae.2024.1404958","DOIUrl":"https://doi.org/10.3389/freae.2024.1404958","url":null,"abstract":"Plants are exquisitely responsive to their local light and temperature environment utilizing these environmental cues to modulate their developmental pathways and adjust growth patterns. This responsiveness is primarily achieved by the intricate interplay between the photoreceptor phyB (phytochrome B) and PIF (PHYTOCHROME INTERACTING FACTORs) transcription factors (TFs), forming a pivotal signaling nexus. phyB and PIFs co-associate in photobodies (PBs) and depending on environmental conditions, PIFs can dissociate from PBs to orchestrate gene expression. Until recently, the mechanisms governing epigenome modifications subsequent to PIF binding to target genes remained elusive. This mini review sheds light on the emerging role of PIFs in mediating epigenome reprogramming by recruiting chromatin regulators (CRs). The formation of numerous different PIF-CR complexes enables precise temporal and spatial control over the gene regulatory networks (GRNs) governing plant-environment interactions. We refer to PIFs as epigenome landscapers, as while they do not directly reprogram the epigenome, they act as critical sequence-specific recruitment platforms for CRs. Intriguingly, in the absence of PIFs, the efficacy of epigenome reprogramming is largely compromised in light and temperature-controlled processes. We have thoroughly examined the composition and function of known PIF-CR complexes and will explore also unanswered questions regarding the precise of locations PIF-mediated epigenome reprogramming within genes, nuclei, and plants.","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"32 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140967516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhanced glucose metabolism in Tet-deficient mouse embryonic stem cells Tet缺陷小鼠胚胎干细胞的葡萄糖代谢增强

Frontiers in epigenetics and epigenomics Pub Date : 2024-05-07 DOI: 10.3389/freae.2024.1245823

Yuhan Yang, Maryn Cavalier, Ashley Suris, Kevin Chen, Claire An, Jingyuan Fan, Logan Rivera, Shaohai Fang, Lei Guo, Yubin Zhou, Yun Huang

{"title":"Enhanced glucose metabolism in Tet-deficient mouse embryonic stem cells","authors":"Yuhan Yang, Maryn Cavalier, Ashley Suris, Kevin Chen, Claire An, Jingyuan Fan, Logan Rivera, Shaohai Fang, Lei Guo, Yubin Zhou, Yun Huang","doi":"10.3389/freae.2024.1245823","DOIUrl":"https://doi.org/10.3389/freae.2024.1245823","url":null,"abstract":"Interactions between epigenetics and metabolites play critical roles in regulating the pluripotency and differentiation of embryonic stem cells. Proper glucose metabolism and DNA methylation are essential for orchestrating accurate lineage specification and the normal functions of embryonic stem cells. However, the impact of Ten-eleven Translocation (TET)-mediated DNA methylation modifications on the metabolism of mouse embryonic stem cells (mESCs) remains less well defined. In this study, we investigated the consequences of Tet triple knockout (Tet-TKO) in mESCs and observed notable alterations in glucose metabolism. These changes were marked by enhanced glucose uptake and glycolysis, likely owing to the upregulation of genes critical for glucose metabolism. Furthermore, Tet-TKO mESCs exhibited defects in glucose-dependent differentiation, suggesting that cells with epigenetic defects might display metabolic vulnerability when exposed to external nutritional cues. Collectively, our findings establish the pivotal role of the TET family of dioxygenases in maintaining proper glucose metabolism and safeguarding stem cell lineage specification, thus enhancing our understanding of the intricate interplay between epigenetic modifications and cellular metabolism in stem cells.","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"30 48","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141004572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Micronutrient regulation of the DNA methylome. 微量营养素对DNA甲基化组的调节。

Frontiers in epigenetics and epigenomics Pub Date : 2024-04-26 eCollection Date: 2024-01-01 DOI: 10.3389/freae.2024.1409355

Tiffany Leesang, Peter Lyon, Joey Pinzone, Luisa Cimmino

{"title":"Micronutrient regulation of the DNA methylome.","authors":"Tiffany Leesang, Peter Lyon, Joey Pinzone, Luisa Cimmino","doi":"10.3389/freae.2024.1409355","DOIUrl":"10.3389/freae.2024.1409355","url":null,"abstract":"The formation, inheritance, and removal of DNA methylation in the genome of mammalian cells is directly regulated by two families of enzymes-DNA methyltransferases (DNMTs) and Ten-Eleven Translocation proteins (TETs). DNMTs generate and maintain the inheritance of 5-methylcytosine (5mC), which is the substrate targeted by the TET enzymes for conversion to 5-hydroxymethylcytosine (5hmC) and its downstream oxidized derivatives. The activity of DNMT and TET is dependent on the availability of micronutrients and metabolite co-factors, including essential vitamins, amino acids, and trace metals, highlighting how DNA methylation levels can be directly enhanced, suppressed, or remodeled via metabolic and nutritional perturbations. Dynamic changes in DNA methylation are required during embryonic development, lineage specification, and maintenance of somatic cell function that can be fine-tuned based on the influence of essential micronutrients. As we age, DNA methylation and hydroxymethylation levels drift in patterning, leading to epigenetic dysregulation and genomic instability that underlies the formation and progression of multiple diseases including cancer. Understanding how DNA methylation can be regulated by micronutrients will have important implications for the maintenance of normal tissue function upon aging, and in the prevention and treatment of diseases for improved health and lifespan.","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"2 ","pages":"1409355"},"PeriodicalIF":0.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121624","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

SWI/SNF chromatin remodelers in prostate cancer progression 前列腺癌进展过程中的 SWI/SNF 染色质重塑因子

Frontiers in epigenetics and epigenomics Pub Date : 2024-01-04 DOI: 10.3389/freae.2023.1337345

Sandra C Ordonez-Rubiano, Brayden P Strohmier, Surbhi Sood, Emily C. Dykhuizen

引用次数: 0

MicroRNAs provide negative feedback and stability in gene regulatory network models of cell-state transitions. microrna在细胞状态转变的基因调控网络模型中提供负反馈和稳定性。

Frontiers in epigenetics and epigenomics Pub Date : 2024-01-01 Epub Date: 2024-10-01 DOI: 10.3389/freae.2024.1473789

Milad Razavi-Mohseni, Michael A Beer

{"title":"MicroRNAs provide negative feedback and stability in gene regulatory network models of cell-state transitions.","authors":"Milad Razavi-Mohseni, Michael A Beer","doi":"10.3389/freae.2024.1473789","DOIUrl":"10.3389/freae.2024.1473789","url":null,"abstract":"The development of multicellular organisms occurs through a series of cell state transitions controlled by gene regulatory networks. Central to these networks are transcription factors (TFs) which bind enhancers and activate the expression of other genes, some of which are also TFs. Gene regulatory networks (GRN) connect TFs and enhancers in a nonlinear circuit capable of producing complex behavior such as bifurcations between stable cell states. Our dynamic network modelling of the Embryonic Stem Cell (ESC) to Definitive Endoderm (DE) transition requires an as yet unknown negative feedback mechanism for stability. Here, we show that cell state specific microRNAs (miRNAs) can provide this negative feedback by inactivating other cell lineage determining TFs (ESC or DE) during the transition. Our model provides a mechanism to maintain stable cell states without requiring a large set of cell-type-specific repressive TFs, of which there are fewer known examples than activators. In support of this model, we use computational models and analyze gene and miRNA expression and chromatin accessibility data from human cell lines to detect enhancers activating the miRNAs consistent with our network model. Our analysis highlights the interplay between TFs and miRNAs during ESC to DE transition and proposes a novel model for gene regulation.","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13004118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147501455","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

HDAC3 regulates the diurnal rhythms of claudin expression and intestinal permeability. HDAC3调节claudin表达和肠通透性的昼夜节律。

Frontiers in epigenetics and epigenomics Pub Date : 2024-01-01 Epub Date: 2024-11-27 DOI: 10.3389/freae.2024.1496999

Hunter Christopher, Jianglin Zhang, Sarah Olanrewaju Oladejo, Samskrathi Aravinda Sharma, Zheng Kuang

{"title":"HDAC3 regulates the diurnal rhythms of claudin expression and intestinal permeability.","authors":"Hunter Christopher, Jianglin Zhang, Sarah Olanrewaju Oladejo, Samskrathi Aravinda Sharma, Zheng Kuang","doi":"10.3389/freae.2024.1496999","DOIUrl":"10.3389/freae.2024.1496999","url":null,"abstract":"Circadian rhythms play an essential role in the regulation of intestinal absorption and barrier function. Tight junctions, including claudins, are fundamental components of the intestinal epithelial barrier. However, the regulatory mechanisms governing their diurnal expression remain poorly understood. Furthermore, the impact of circadian rhythms on intestinal permeability through claudin modulation has yet to be fully explored. Here we investigated the expression and the diurnal rhythms of claudin transcripts in the intestinal epithelium. We identified histone deacetylase 3 (HDAC3) as an epigenetic regulator that represses claudin expression and drives the diurnal rhythms via histone deacetylation. Loss of HDAC3 leads to increased intestinal permeability and dampened its diurnal rhythm. We further revealed that HDAC3 affects the basolateral localization of claudin-3. Together, our findings give insights into epigenetic modification in regulating tight junction and its diurnal rhythms, providing targets for therapeutic mediations in gastrointestinal disorders.","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786353","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