{"title":"PLK-1 Interacting Checkpoint Helicase, PICH, Mediates Cellular Oxidative Stress Response.","authors":"Anindita Dutta, Apurba Das, Deepa Bisht, Vijendra Arya, Rohini Muthuswami","doi":"10.3390/epigenomes6040036","DOIUrl":"https://doi.org/10.3390/epigenomes6040036","url":null,"abstract":"<p><p>Cells respond to oxidative stress by elevating the levels of antioxidants, signaling, and transcriptional regulation, often implemented by chromatin remodeling proteins. The study presented here shows that the expression of PICH, a Rad54-like helicase belonging to the ATP-dependent chromatin remodeling protein family, is upregulated during oxidative stress in HeLa cells. We also show that PICH regulates the expression of Nrf2, a transcription factor regulating antioxidant response in both the absence and presence of oxidative stress. The overexpression of <i>PICH</i> in <i>PICH</i>-depleted cells restored <i>Nrf2</i> as well as antioxidant gene expression. In turn, Nrf2 regulated the expression of <i>PICH</i> in the presence of oxidative stress. ChIP experiments showed that PICH is present on the <i>Nrf2</i> as well as antioxidant gene promoters, suggesting that the protein might be regulating the expression of these genes directly by binding to the DNA sequences. In addition, Nrf2 and histone acetylation (H3K27ac) also played a role in activating transcription in the presence of oxidative stress. Both Nrf2 and H3K27ac were found to be present on <i>PICH</i> and antioxidant promoters. Their occupancy was dependent on the <i>PICH</i> expression as fold enrichment was found to be decreased in <i>PICH</i>-depleted cells. PICH ablation led to the reduced expression of Nrf2 and impaired antioxidant response, leading to increased ROS content and thus showing PICH is essential for the cell to respond to oxidative stress.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9590091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40678098","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}
EpigenomesPub Date : 2022-10-12DOI: 10.3390/epigenomes6040035
Anna Fiselier, Boseon Byeon, Yaroslav Ilnytskyy, Olga Kovalchuk, Igor Kovalchuk
{"title":"Scatter Irradiation of Rat Brain Triggers Sex- and Brain Region-Specific Changes in the Expression of Non-Coding RNA Fragments.","authors":"Anna Fiselier, Boseon Byeon, Yaroslav Ilnytskyy, Olga Kovalchuk, Igor Kovalchuk","doi":"10.3390/epigenomes6040035","DOIUrl":"https://doi.org/10.3390/epigenomes6040035","url":null,"abstract":"<p><p>Non-coding RNA fragments (ncRFs) are small RNA fragments processed from non-coding RNAs (ncRNAs). ncRFs have various functions and are commonly tissue-specific, and their processing is altered by exposure to stress. Information about ncRFs in the brain is scarce. Recently, we reported the brain region-specific and sex-specific expression of ncRNAs and their processing into ncRFs. Here, we analyzed the expression of ncRFs in the frontal cortex (FC), hippocampus (HIP), and cerebellum (CER) of male and female rats exposed to scatter radiation. We found multiple brain region- and sex-specific changes in response to scatter radiation. Specifically, we observed decreased miRNA expression and the increased expression of ra-ncRNA reads in HIP and CER, as well as an increased number of mtR-NA-associated reads in HIP. We also observed the appearance of sense-intronic ncRNAs-in females, in HIP and FC, and in males, in CER. In this work, we also show that tRNA-GlyGCC and tRNA-GlyCCC are most frequently processed to tRFs, in CER in females, as compared to males. An analysis of the targeted pathways revealed that tRFs and snoRFs in scatter radiation samples mapped to genes in several pathways associated with various neuronal functions. While in HIP and CER these pathways were underrepresented, in FC, they were overrepresented. Such changes may play an important role in pathologies that develop in response to scatter radiation, the effect known as \"radio-brain\", and may in part explain the sex-specific differences observed in animals and humans exposed to radiation and scatter radiation.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9624364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40678097","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}
EpigenomesPub Date : 2022-10-05DOI: 10.3390/epigenomes6040034
Philippe Johann To Berens, Geoffrey Schivre, Marius Theune, Jackson Peter, Salimata Ousmane Sall, Jérôme Mutterer, Fredy Barneche, Clara Bourbousse, Jean Molinier
{"title":"Advanced Image Analysis Methods for Automated Segmentation of Subnuclear Chromatin Domains.","authors":"Philippe Johann To Berens, Geoffrey Schivre, Marius Theune, Jackson Peter, Salimata Ousmane Sall, Jérôme Mutterer, Fredy Barneche, Clara Bourbousse, Jean Molinier","doi":"10.3390/epigenomes6040034","DOIUrl":"https://doi.org/10.3390/epigenomes6040034","url":null,"abstract":"<p><p>The combination of ever-increasing microscopy resolution with cytogenetical tools allows for detailed analyses of nuclear functional partitioning. However, the need for reliable qualitative and quantitative methodologies to detect and interpret chromatin sub-nuclear organization dynamics is crucial to decipher the underlying molecular processes. Having access to properly automated tools for accurate and fast recognition of complex nuclear structures remains an important issue. Cognitive biases associated with human-based curation or decisions for object segmentation tend to introduce variability and noise into image analysis. Here, we report the development of two complementary segmentation methods, one semi-automated (<i>iCRAQ</i>) and one based on deep learning (<i>Nucl.Eye.D</i>), and their evaluation using a collection of <i>A. thaliana</i> nuclei with contrasted or poorly defined chromatin compartmentalization. Both methods allow for fast, robust and sensitive detection as well as for quantification of subtle nucleus features. Based on these developments, we highlight advantages of semi-automated and deep learning-based analyses applied to plant cytogenetics.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9624336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40678096","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":"Modulation of DNA Methylation/Demethylation Reactions Induced by Nutraceuticals and Pollutants of Exposome Can Promote a C > T Mutation in the Breast Cancer Predisposing Gene PALB2","authors":"Florestan Courant, Gwenola Bougras-Cartron, Caroline Abadie, Jean-Sébastien Frenel, Pierre-François Cartron","doi":"10.3390/epigenomes6040032","DOIUrl":"https://doi.org/10.3390/epigenomes6040032","url":null,"abstract":"<p><p>Background: Deregulation of DNA methylation/demethylation reactions may be the source of C > T mutation via active deamination of 5-methylcytosine to thymine. Exposome, that is to say, the totality of exposures to which an individual is subjected during their life, can deregulate these reactions. Thus, one may wonder whether the exposome can induce C > T mutations in the breast cancer-predisposing gene PALB2. Methods: Our work is based on the exposure of MCF10A mammary epithelial cells to seven compounds of our exposome (folate, Diuron, glyphosate, PFOA, iron, zinc, and ascorbic acid) alone or in cocktail. The qMSRE and RMS techniques were used to study the impact of these exposures on the level of methylation and mutation of the PALB2 gene. Results: Here, we have found that exposome compounds (nutriments, ions, pollutants) promoting the cytosine methylation and the 5-methylcytosine deamination have the ability to promote a specific C > T mutation in the PALB2 gene. Interestingly, we also noted that the addition of exposome compounds promoting the TET-mediated conversion of 5-methylcytosine (Ascorbic acid and iron) abrogates the presence of C > T mutation in the PALB2 gene. Conclusions: Our study provides a proof of concept supporting the idea that exposomes can generate genetic mutation by affecting DNA methylation/demethylation.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9590087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9127105","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}
EpigenomesPub Date : 2022-09-27DOI: 10.3390/epigenomes6040030
Le Zhang, Emma M Rath, Yuen Yee Cheng
{"title":"The Use of Epigenetic Biomarkers as Diagnostic and Therapeutic Options.","authors":"Le Zhang, Emma M Rath, Yuen Yee Cheng","doi":"10.3390/epigenomes6040030","DOIUrl":"https://doi.org/10.3390/epigenomes6040030","url":null,"abstract":"<p><p>The last few decades have brought tremendous advances in the mechanisms of epigenetic regulation, with DNA methylation, histone methylation and acetylation, microRNAs and other noncoding RNAs being among the most prominent [...].</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9590074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40567345","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}
EpigenomesPub Date : 2022-08-24DOI: 10.3390/epigenomes6030026
Yasuhiro Fujiwara, Mary Ann Handel, Yuki Okada
{"title":"R-Loop Formation in Meiosis: Roles in Meiotic Transcription-Associated DNA Damage.","authors":"Yasuhiro Fujiwara, Mary Ann Handel, Yuki Okada","doi":"10.3390/epigenomes6030026","DOIUrl":"https://doi.org/10.3390/epigenomes6030026","url":null,"abstract":"<p><p>Meiosis is specialized cell division during gametogenesis that produces genetically unique gametes via homologous recombination. Meiotic homologous recombination entails repairing programmed 200-300 DNA double-strand breaks generated during the early prophase. To avoid interference between meiotic gene transcription and homologous recombination, mammalian meiosis is thought to employ a strategy of exclusively transcribing meiotic or post-meiotic genes before their use. Recent studies have shown that R-loops, three-stranded DNA/RNA hybrid nucleotide structures formed during transcription, play a crucial role in transcription and genome integrity. Although our knowledge about the function of R-loops during meiosis is limited, recent findings in mouse models have suggested that they play crucial roles in meiosis. Given that defective formation of an R-loop can cause abnormal transcription and transcription-coupled DNA damage, the precise regulatory network of R-loops may be essential in vivo for the faithful progression of mammalian meiosis and gametogenesis.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9498298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33469475","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":"Experimental and Computational Approaches for Non-CpG Methylation Analysis.","authors":"Deepa Ramasamy, Arunagiri Kuha Deva Magendhra Rao, Thangarajan Rajkumar, Samson Mani","doi":"10.3390/epigenomes6030024","DOIUrl":"https://doi.org/10.3390/epigenomes6030024","url":null,"abstract":"<p><p>Cytosine methylation adjacent to adenine, thymine, and cytosine residues but not guanine of the DNA is distinctively known as non-CpG methylation. This CA/CT/CC methylation accounts for 15% of the total cytosine methylation and varies among different cell and tissue types. The abundance of CpG methylation has largely concealed the role of non-CpG methylation. Limitations in the early detection methods could not distinguish CpG methylation from non-CpG methylation. Recent advancements in enrichment strategies and high throughput sequencing technologies have enabled the detection of non-CpG methylation. This review discusses the advanced experimental and computational approaches to detect and describe the genomic distribution and function of non-CpG methylation. We present different approaches such as enzyme-based and antibody-based enrichment, which, when coupled, can also improve the sensitivity and specificity of non-CpG detection. We also describe the current bioinformatics pipelines and their specific application in computing and visualizing the imbalance of CpG and non-CpG methylation. Enrichment modes and the computational suites need to be further developed to ease the challenges of understanding the functional role of non-CpG methylation.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9397002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40649120","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}
EpigenomesPub Date : 2022-08-12DOI: 10.3390/epigenomes6030023
Chet H Loh, Gert Jan C Veenstra
{"title":"The Role of Polycomb Proteins in Cell Lineage Commitment and Embryonic Development.","authors":"Chet H Loh, Gert Jan C Veenstra","doi":"10.3390/epigenomes6030023","DOIUrl":"https://doi.org/10.3390/epigenomes6030023","url":null,"abstract":"<p><p>Embryonic development is a highly intricate and complex process. Different regulatory mechanisms cooperatively dictate the fate of cells as they progress from pluripotent stem cells to terminally differentiated cell types in tissues. A crucial regulator of these processes is the Polycomb Repressive Complex 2 (PRC2). By catalyzing the mono-, di-, and tri-methylation of lysine residues on histone H3 tails (H3K27me3), PRC2 compacts chromatin by cooperating with Polycomb Repressive Complex 1 (PRC1) and represses transcription of target genes. Proteomic and biochemical studies have revealed two variant complexes of PRC2, namely PRC2.1 which consists of the core proteins (EZH2, SUZ12, EED, and RBBP4/7) interacting with one of the Polycomb-like proteins (MTF2, PHF1, PHF19), and EPOP or PALI1/2, and PRC2.2 which contains JARID2 and AEBP2 proteins. MTF2 and JARID2 have been discovered to have crucial roles in directing and recruiting PRC2 to target genes for repression in embryonic stem cells (ESCs). Following these findings, recent work in the field has begun to explore the roles of different PRC2 variant complexes during different stages of embryonic development, by examining molecular phenotypes of PRC2 mutants in both in vitro (2D and 3D differentiation) and in vivo (knock-out mice) assays, analyzed with modern single-cell omics and biochemical assays. In this review, we discuss the latest findings that uncovered the roles of different PRC2 proteins during cell-fate and lineage specification and extrapolate these findings to define a developmental roadmap for different flavors of PRC2 regulation during mammalian embryonic development.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9397020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40649119","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}
EpigenomesPub Date : 2022-07-20DOI: 10.3390/epigenomes6030019
Ryszard Maleszka
{"title":"Clinical Epigenetics on the Baltic Coast.","authors":"Ryszard Maleszka","doi":"10.3390/epigenomes6030019","DOIUrl":"https://doi.org/10.3390/epigenomes6030019","url":null,"abstract":"<p><p>This report summarizes the proceedings of the inaugural Clinical Epigenetics Conference that was held in Szczecin, Poland, from 8 June 2022. With focus on epigenetic diseases whose causes, progression, and prognosis are associated with aberrant epigenomic alterations, the meeting was a timely forum to discuss recent progress in this rapidly evolving field and consider avenues for converting experimental data into clinical reality that would be beneficial for patients. The wealth of the presented data was an impressive showcase of the enormous challenges faced by researchers in their quest for understanding the benefits and limitations of the available information in the medical context. A shared view among the participants was that merging the current state of knowledge with clinical applications will be promptly achieved.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40647022","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}
EpigenomesPub Date : 2022-07-12DOI: 10.3390/epigenomes6030017
Tighe Bloskie, Kenneth B Storey
{"title":"DNA Hypomethylation May Contribute to Metabolic Recovery of Frozen Wood Frog Brains.","authors":"Tighe Bloskie, Kenneth B Storey","doi":"10.3390/epigenomes6030017","DOIUrl":"https://doi.org/10.3390/epigenomes6030017","url":null,"abstract":"<p><p>Transcriptional suppression is characteristic of extreme stress responses, speculated to preserve energetic resources in the maintenance of hypometabolism. In recent years, epigenetic regulation has become heavily implicated in stress adaptation of many animals, including supporting freeze tolerance of the wood frog (Rana sylvatica). However, nervous tissues are frequently lacking in these multi-tissue analyses which warrants investigation. The present study examines the role of DNA methylation, a core epigenetic mechanism, in the response of wood frog brains to freezing. We use immunoblot analysis to track the relative expression of DNA methyltransferases (DNMT), methyl-CpG-binding domain (MBD) proteins and ten-eleven-translocation (TET) demethylases across the freeze-thaw cycle in R. sylvatica brain, including selected comparisons to freeze-associated sub-stresses (anoxia and dehydration). Global methyltransferase activities and 5-hmC content were also assessed. The data show coordinated evidence for DNA hypomethylation in wood frog brains during freeze-recovery through the combined roles of depressed DNMT3A/3L expression driving lowered DNMT activity and increased TET2/3 levels leading to elevated 5-hmC genomic content (p < 0.05). Raised levels of DNMT1 during high dehydration were also noteworthy. The above suggest that alleviation of transcriptionally repressive 5-mC DNA methylation is a necessary component of the wood frog freeze-thaw cycle, potentially facilitating the resumption of a normoxic transcriptional state as frogs thaw and resume normal metabolic activities.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9419109","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}