Frontiers in epigenetics and epigenomics最新文献

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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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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
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
{"title":"SWI/SNF chromatin remodelers in prostate cancer progression","authors":"Sandra C Ordonez-Rubiano, Brayden P Strohmier, Surbhi Sood, Emily C. Dykhuizen","doi":"10.3389/freae.2023.1337345","DOIUrl":"https://doi.org/10.3389/freae.2023.1337345","url":null,"abstract":"Prostate cancer (PCa) is the most commonly diagnosed cancer and the second most common cause of cancer-related deaths in men in the US. The majority of PCa cases arise in the luminal cells of the prostate and develop into adenocarcinoma. Primary PCas are heterogeneous and have alterations in a variety of tumor suppressors and oncogenes; however, the vast majority are dependent on gene expression regulation by androgen receptor (AR), making it the focus for most targeted therapy development. As the incidence of PCa cases resistant to AR-targeted therapies rises, there is renewed attention on how additional genetic and epigenetic alterations contribute to PCa progression and resistance. In this review we summarize the efforts made over the past 20 years to dissect the function of the SWI/SNF chromatin remodelers in PCa. We mainly focus on how SWI/SNF complexes regulate different aspects of AR signaling, facilitate other key drivers in PCa, promote the advancement of the disease, and regulate the tumor microenvironment.","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139386191","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
Subcellular one carbon metabolism in cancer, aging and epigenetics. 癌症、衰老和表观遗传学中的亚细胞一碳代谢。
Frontiers in epigenetics and epigenomics Pub Date : 2024-01-01 Epub Date: 2024-07-31 DOI: 10.3389/freae.2024.1451971
Tiziano Bernasocchi, Raul Mostoslavsky
{"title":"Subcellular one carbon metabolism in cancer, aging and epigenetics.","authors":"Tiziano Bernasocchi, Raul Mostoslavsky","doi":"10.3389/freae.2024.1451971","DOIUrl":"10.3389/freae.2024.1451971","url":null,"abstract":"<p><p>The crosstalk between metabolism and epigenetics is an emerging field that is gaining importance in different areas such as cancer and aging, where changes in metabolism significantly impacts the cellular epigenome, in turn dictating changes in chromatin as an adaptive mechanism to bring back metabolic homeostasis. A key metabolic pathway influencing an organism's epigenetic state is one-carbon metabolism (OCM), which includes the folate and methionine cycles. Together, these cycles generate S-adenosylmethionine (SAM), the universal methyl donor essential for DNA and histone methylation. SAM serves as the sole methyl group donor for DNA and histone methyltransferases, making it a crucial metabolite for chromatin modifications. In this review, we will discuss how SAM and its byproduct, S-adenosylhomocysteine (SAH), along with the enzymes and cofactors involved in OCM, may function in the different cellular compartments, particularly in the nucleus, to directly regulate the epigenome in aging and cancer.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142285","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
Beyond genetics: can micro and nanoplastics induce epigenetic and gene-expression modifications? 超越遗传学:微塑料和纳米塑料能诱导表观遗传和基因表达修饰吗?
Frontiers in epigenetics and epigenomics Pub Date : 2023-08-21 DOI: 10.3389/freae.2023.1241583
A. Poma, P. Morciano, Massimo Aloisi
{"title":"Beyond genetics: can micro and nanoplastics induce epigenetic and gene-expression modifications?","authors":"A. Poma, P. Morciano, Massimo Aloisi","doi":"10.3389/freae.2023.1241583","DOIUrl":"https://doi.org/10.3389/freae.2023.1241583","url":null,"abstract":"Plastic pollution is becoming a worldwide crisis. It can be found in all environmental matrices, from the seas to the oceans, from dry land to the air we breathe. Because of the various types of plastic polymers and waste degradation methods, the types of plastic particles we are exposed to are quite diverse. Plants and animals are continuously exposed to them, and as the top of the food chain, humans are as well. There are numerous studies that confirm the toxicity of these contaminants, yet there is still a significant vacuum in their epigenetics effects and gene expression modifications. Here we collect studies published to date on the epigenetics effects and gene expression modulation induced by micro and nanoplastics. Although published data are still scarce, it is becoming evident that micro- and nanoplastics, whether acutely or chronically administered, do indeed cause such changes in various model organisms. A future challenge is represented by continuing and deepening these studies to better define the molecular mechanisms underlying the observed toxic effects and above all to translate these results to humans to understand their impact on health.","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125878046","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
Generation of site-specific ubiquitinated histones through chemical ligation to probe the specificities of histone deubiquitinases 通过化学连接产生位点特异性泛素化组蛋白,探索组蛋白去泛素化酶的特异性
Frontiers in epigenetics and epigenomics Pub Date : 2023-07-31 DOI: 10.3389/freae.2023.1238154
N. Alafaleq, Yun-Seok Choi, B. Atanassov, R. E. Cohen, T. Yao
{"title":"Generation of site-specific ubiquitinated histones through chemical ligation to probe the specificities of histone deubiquitinases","authors":"N. Alafaleq, Yun-Seok Choi, B. Atanassov, R. E. Cohen, T. Yao","doi":"10.3389/freae.2023.1238154","DOIUrl":"https://doi.org/10.3389/freae.2023.1238154","url":null,"abstract":"The attachment of mono-ubiquitin to histones as a post-translational modification plays important roles in regulating chromatin structure and function. Like other epigenetic modifications, the site of ubiquitin attachment is critically important in determining its functional outcome. Depending on the type of histone and the specific lysine residue that is modified, ubiquitination acts in diverse pathways including DNA damage repair, transcription elongation, and transcription repression. Specific reader, writer and eraser activities have evolved to distinguish nucleosomes by ubiquitination of different sites. To facilitate biochemical studies of ubiquitinated nucleosomes, we have developed an efficient strategy to chemically ligate intact ubiquitin and histone proteins at specific sites to generate near-native ubiquitin-histone conjugates. Because these chemically-ligated ubiquitin conjugates are hydrolysable, they enabled us to characterize in vitro the specificities of several histone deubiquitinases. To gain insight into the mechanisms that contribute to the specificities of these deubiquitinases, we used a free Ub sensor-based real-time assay to determine their Michaelis-Menten kinetics. Our results confirmed previously reported specificities of BAP1 and USP22, but also revealed specificities of other histone deubiquitinases that have been less well defined in the literature.","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130113574","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
Triggers and mediators of epigenetic remodeling in plants 植物表观遗传重塑的触发因子和介质
Frontiers in epigenetics and epigenomics Pub Date : 2023-05-23 DOI: 10.3389/freae.2023.1188733
L. Comai
{"title":"Triggers and mediators of epigenetic remodeling in plants","authors":"L. Comai","doi":"10.3389/freae.2023.1188733","DOIUrl":"https://doi.org/10.3389/freae.2023.1188733","url":null,"abstract":"Plant epigenetic studies have revealed that developmental or environmental events can trigger both local and global epigenetic remodeling. In multiple cases, transposable elements (TE) respond to the trigger and act as mediators. Epigenetic remodeling results in mitotically and even meiotically persistent states that impact phenotype and could contribute to its plasticity. The challenge is to understand the mechanisms that trigger and mediate remodeling, their evolutionary role, and their potential in breeding.","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134273785","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
Grand challenge in chromatin epigenomics: everything, everywhere, all at once 染色质表观基因组学面临的巨大挑战:所有的东西,所有的地方,同时发生
Frontiers in epigenetics and epigenomics Pub Date : 2023-05-05 DOI: 10.3389/freae.2023.1195690
Sharon Y. R. Dent
{"title":"Grand challenge in chromatin epigenomics: everything, everywhere, all at once","authors":"Sharon Y. R. Dent","doi":"10.3389/freae.2023.1195690","DOIUrl":"https://doi.org/10.3389/freae.2023.1195690","url":null,"abstract":"Our understanding of the regulation and functions of histone modifications has come a long way since they were first reported in the mid-1960s. So too has our understanding of the importance of DNA methylation, histone variants, nucleosome locations and arrangements, and progressively higher order structures that impact when and where DNA-templated processes take place. Recent advances have even allowed the first ever complete sequencing and epigenomic profiles of individual chromosomes from telomere to telomere, including highly repetitive regions that were previously refractory to analysis. The regulatory power of chromatin organization for gene transcription, DNA replication, recombination and repair is undisputable. Still, an ongoing challenge is to understand the full spectrum of changes (everything) that impact processes in cells and tissues (everywhere) and how each change impacts others (all at once).","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130703430","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
The epigenetic landscape: An evolving concept 表观遗传景观:一个进化的概念
Frontiers in epigenetics and epigenomics Pub Date : 2023-03-20 DOI: 10.3389/freae.2023.1176449
S. Henikoff
{"title":"The epigenetic landscape: An evolving concept","authors":"S. Henikoff","doi":"10.3389/freae.2023.1176449","DOIUrl":"https://doi.org/10.3389/freae.2023.1176449","url":null,"abstract":"The epigenetic landscape was a visual metaphor introduced in the mid-twentieth century to illustrate the genetic control of embryonic differentiation. Although the popular understanding of epigenetics has since expanded to include gene and chromosomal mechanisms in all contexts, the landscape metaphor provides a unifying concept centered around processes that establish and maintain cellular memory. However, over the decades the term epigenetics has been also used to describe some non-genetic processes that bear little or no resemblance to the traditional concept of an epigenetic landscape. By establishing Frontiers in Epigenetics and Epigenomics, we aim to provide authors and readers a forum and an outlet for research that is centered around the original concept of an epigenetic landscape. Thanks in large part to exciting advances in epigenomic technologies, we expect that a deeper understanding of cellular memory will translate into new strategies for medicine, agriculture, and environmental health.","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132578774","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
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