{"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":"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/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}
{"title":"<i>A hypothetical model</i>: Chromatin remodelers couple with acetyltransferases to trigger the elongation of RNA polymerase II (pol II).","authors":"Gongyi Zhang","doi":"10.3389/freae.2024.1439973","DOIUrl":"10.3389/freae.2024.1439973","url":null,"abstract":"<p><p>Transcription is one of the central dogmas of life. Most genes in eukaryotes are transcribed by RNA polymerase II (Pol II). For Pol II to transcribe along the gene body, it must overcome nucleosomes, which are barriers for Pol II. It is still a mystery how Pol II ejects nucleosomes during transcription elongation. I hypothesize that a group of chromatin remodelers (SWI/SNF, RSC, SWR1, INO80) carry a group of histone acetyltransferases (NuA4, Spt-Ada-Gcn-acetyltransferase, NuA3) to deposit acetyl-groups on histone tails to generate pan-acetylated nucleosomes or fragile nucleosomes along gene bodies for Pol II to transcribe. Specifically, for the first round of transcription, the RSC complex works with NuA4 to acetylate histone tails of H2A and H4; the SWI/SNF complex carries SAGA to add acetyl-groups to histone tails of H2B and H3. For the second and subsequent rounds, SWR1 pairs with a piccolo NuA4 to acetylate the histone tails of H2A and H4 of newly inserted nucleosomes, while INO80 pairs with NuA3 to acetylate the histone tails of H2B and H3 within newly inserted nucleosomes along the gene body. After the mission is accomplished, ISW1b couples with Rpd3s to remove acetyl groups on H2A and H4, while CHD1 carries HDA1 along the gene body to remove acetyl groups on H2B and H3.</p>","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/PMC12712627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145806608","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":"Enhancing sensitivity and versatility of Tn5-based single cell omics.","authors":"Isabelle Seufert, Pooja Sant, Katharina Bauer, Afzal P Syed, Karsten Rippe, Jan-Philipp Mallm","doi":"10.3389/freae.2023.1245879","DOIUrl":"10.3389/freae.2023.1245879","url":null,"abstract":"<p><p>The analysis of chromatin features in single cells centers around Tn5 transposase and exploits its activity to simultaneously fragment target DNA and integrate adapter sequences of choice. This reaction provides a direct readout in the assay for transposase-accessible chromatin in single cells (scATAC-seq) to map open chromatin loci. However, a current limitation is the sparse coverage of these open sites in a given single cell by droplet-based methods. Thus, enhancing Tn5 activity to improve genomic coverage of scATAC-seq or facilitating multi-omics readouts of chromatin features via Tn5 together with the transcriptome is of great interest. Here, we address these issues by optimizing scATAC-seq for an increased number of integrations per cell. In addition, we provide a protocol that combines mapping of histone modification with scRNA-seq from the same cell by targeting Tn5 to antibody-bound chromatin epitopes. Our experimental workflows improve the results obtained from the downstream data analysis and serve to better resolve epigenetic heterogeneity and transcription regulation in single cells.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"1 ","pages":"1245879"},"PeriodicalIF":0.0,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121602","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":"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":"1 1","pages":"0"},"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}
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":"11 1","pages":"0"},"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}
{"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":"120 1","pages":"0"},"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}
{"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":"1 1","pages":"0"},"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}
{"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":"159 1","pages":"0"},"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}
Spencer E Escobedo, Sarah E McGovern, Juan P Jauregui-Lozano, Sarah C Stanhope, Paul Anik, Kratika Singhal, Ryan DeBernardis, Vikki M Weake
{"title":"Targeted RNAi screen identifies transcriptional mechanisms that prevent premature degeneration of adult photoreceptors.","authors":"Spencer E Escobedo, Sarah E McGovern, Juan P Jauregui-Lozano, Sarah C Stanhope, Paul Anik, Kratika Singhal, Ryan DeBernardis, Vikki M Weake","doi":"10.3389/freae.2023.1187980","DOIUrl":"10.3389/freae.2023.1187980","url":null,"abstract":"<p><p>Aging is associated with a decline in visual function and increased prevalence of ocular disease, correlating with changes in the transcriptome and epigenome of cells in the eye. Here, we sought to identify the transcriptional mechanisms that are necessary to maintain photoreceptor viability and function during aging. To do this, we performed a targeted photoreceptor-specific RNAi screen in <i>Drosophila</i> to identify transcriptional regulators whose knockdown results in premature, age-dependent retinal degeneration. From an initial set of 155 RNAi lines each targeting a unique gene and spanning a diverse set of transcription factors, chromatin remodelers, and histone modifiers, we identified 18 high-confidence target genes whose decreased expression in adult photoreceptors leads to premature and progressive retinal degeneration. These 18 target genes were enriched for factors involved in the regulation of transcription initiation, pausing, and elongation, suggesting that these processes are essential for maintaining the health of aging photoreceptors. To identify the genes regulated by these factors, we profiled the photoreceptor transcriptome in a subset of lines. Strikingly, two of the 18 target genes, <i>Spt5</i> and <i>domino</i>, show similar changes in gene expression to those observed in photoreceptors with advanced age. Together, our data suggest that dysregulation of factors involved in transcription initiation and elongation plays a key role in shaping the transcriptome of aging photoreceptors. Further, our findings indicate that the age-dependent changes in gene expression not only correlate but might also contribute to an increased risk of retinal degeneration.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10603763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71416494","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}