{"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}
EpigenomesPub Date : 2022-10-04DOI: 10.3390/epigenomes6040033
Haley E Hanson, Andrea L Liebl
{"title":"The Mutagenic Consequences of DNA Methylation within and across Generations.","authors":"Haley E Hanson, Andrea L Liebl","doi":"10.3390/epigenomes6040033","DOIUrl":"10.3390/epigenomes6040033","url":null,"abstract":"<p><p>DNA methylation is an epigenetic modification with wide-ranging consequences across the life of an organism. This modification can be stable, persisting through development despite changing environmental conditions. However, in other contexts, DNA methylation can also be flexible, underlying organismal phenotypic plasticity. One underappreciated aspect of DNA methylation is that it is a potent mutagen; methylated cytosines mutate at a much faster rate than other genetic motifs. This mutagenic property of DNA methylation has been largely ignored in eco-evolutionary literature, despite its prevalence. Here, we explore how DNA methylation induced by environmental and other factors could promote mutation and lead to evolutionary change at a more rapid rate and in a more directed manner than through stochastic genetic mutations alone. We argue for future research on the evolutionary implications of DNA methylation driven mutations both within the lifetime of organisms, as well as across timescales.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9624357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40567347","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":null,"pages":null},"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 : 2022-09-28DOI: 10.3390/epigenomes6040031
Valentine Chapelle, Frédéric Silvestre
{"title":"Population Epigenetics: The Extent of DNA Methylation Variation in Wild Animal Populations.","authors":"Valentine Chapelle, Frédéric Silvestre","doi":"10.3390/epigenomes6040031","DOIUrl":"10.3390/epigenomes6040031","url":null,"abstract":"<p><p>Population epigenetics explores the extent of epigenetic variation and its dynamics in natural populations encountering changing environmental conditions. In contrast to population genetics, the basic concepts of this field are still in their early stages, especially in animal populations. Epigenetic variation may play a crucial role in phenotypic plasticity and local adaptation as it can be affected by the environment, it is likely to have higher spontaneous mutation rate than nucleotide sequences do, and it may be inherited via non-mendelian processes. In this review, we aim to bring together natural animal population epigenetic studies to generate new insights into ecological epigenetics and its evolutionary implications. We first provide an overview of the extent of DNA methylation variation and its autonomy from genetic variation in wild animal population. Second, we discuss DNA methylation dynamics which create observed epigenetic population structures by including basic population genetics processes. Then, we highlight the relevance of DNA methylation variation as an evolutionary mechanism in the extended evolutionary synthesis. Finally, we suggest new research directions by highlighting gaps in the knowledge of the population epigenetics field. As for our results, DNA methylation diversity was found to reveal parameters that can be used to characterize natural animal populations. Some concepts of population genetics dynamics can be applied to explain the observed epigenetic structure in natural animal populations. The set of recent advancements in ecological epigenetics, especially in transgenerational epigenetic inheritance in wild animal population, might reshape the way ecologists generate predictive models of the capacity of organisms to adapt to changing environments.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9589984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40567346","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":null,"pages":null},"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 : 2022-09-15DOI: 10.3390/epigenomes6030029
Susana M Contreras, Romina T Zambrano Siri, Elías M Rivera, Constanza Cristaldi, Laura Kamenetzky, Kami Kim, Marina Clemente, Josefina Ocampo, Laura Vanagas, Sergio O Angel
{"title":"Architecture, Chromatin and Gene Organization of <i>Toxoplasma gondii</i> Subtelomeres.","authors":"Susana M Contreras, Romina T Zambrano Siri, Elías M Rivera, Constanza Cristaldi, Laura Kamenetzky, Kami Kim, Marina Clemente, Josefina Ocampo, Laura Vanagas, Sergio O Angel","doi":"10.3390/epigenomes6030029","DOIUrl":"10.3390/epigenomes6030029","url":null,"abstract":"<p><p>Subtelomeres (ST) are chromosome regions that separate telomeres from euchromatin and play relevant roles in various biological processes of the cell. While their functions are conserved, ST structure and genetic compositions are unique to each species. This study aims to identify and characterize the subtelomeric regions of the 13 <i>Toxoplasma gondii</i> chromosomes of the Me49 strain. Here, STs were defined at chromosome ends based on poor gene density. The length of STs ranges from 8.1 to 232.4 kbp, with a gene density of 0.049 genes/kbp, lower than the Me49 genome (0.15 kbp). Chromatin organization showed that H3K9me3, H2A.X, and H3.3 are highly enriched near telomeres and the 5' end of silenced genes, decaying in intensity towards euchromatin. H3K4me3 and H2A.Z/H2B.Z are shown to be enriched in the 5' end of the ST genes. Satellite DNA was detected in almost all STs, mainly the sat350 family and a novel satellite named sat240. Beyond the STs, only short dispersed fragments of sat240 and sat350 were found. Within STs, there were 12 functional annotated genes, 59 with unknown functions (Hypothetical proteins), 15 from multigene FamB, and 13 from multigene family FamC. Some genes presented low interstrain synteny associated with the presence of satellite DNA. Orthologues of FamB and FamC were also detected in <i>Neospora caninum</i> and <i>Hammondia hammondi</i>. A re-analysis of previous transcriptomic data indicated that ST gene expression is strongly linked to the adaptation to different situations such as extracellular passage (evolve and resequencing study) and changes in metabolism (lack of acetyl-CoA cofactor). In conclusion, the ST region of the <i>T. gondii</i> chromosomes was defined, the STs genes were determined, and it was possible to associate them with high interstrain plasticity and a role in the adaptability of <i>T. gondii</i> to environmental changes.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9498087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33469407","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 : 2022-09-06DOI: 10.3390/epigenomes6030028
Beatriz German, Leigh Ellis
{"title":"Polycomb Directed Cell Fate Decisions in Development and Cancer.","authors":"Beatriz German, Leigh Ellis","doi":"10.3390/epigenomes6030028","DOIUrl":"10.3390/epigenomes6030028","url":null,"abstract":"<p><p>The polycomb group (PcG) proteins are a subset of transcription regulators highly conserved throughout evolution. Their principal role is to epigenetically modify chromatin landscapes and control the expression of master transcriptional programs to determine cellular identity. The two mayor PcG protein complexes that have been identified in mammals to date are Polycomb Repressive Complex 1 (PRC1) and 2 (PRC2). These protein complexes selectively repress gene expression via the induction of covalent post-translational histone modifications, promoting chromatin structure stabilization. PRC2 catalyzes the histone H3 methylation at lysine 27 (H3K27me1/2/3), inducing heterochromatin structures. This activity is controlled by the formation of a multi-subunit complex, which includes enhancer of zeste (EZH2), embryonic ectoderm development protein (EED), and suppressor of zeste 12 (SUZ12). This review will summarize the latest insights into how PRC2 in mammalian cells regulates transcription to orchestrate the temporal and tissue-specific expression of genes to determine cell identity and cell-fate decisions. We will specifically describe how PRC2 dysregulation in different cell types can promote phenotypic plasticity and/or non-mutational epigenetic reprogramming, inducing the development of highly aggressive epithelial neuroendocrine carcinomas, including prostate, small cell lung, and Merkel cell cancer. With this, EZH2 has emerged as an important actionable therapeutic target in such cancers.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9497807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33469410","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 : 2022-08-26DOI: 10.3390/epigenomes6030027
Catherine A Dennen, Kenneth Blum, Abdalla Bowirrat, Jag Khalsa, Panayotis K Thanos, David Baron, Rajendra D Badgaiyan, Ashim Gupta, Eric R Braverman, Mark S Gold
{"title":"Neurogenetic and Epigenetic Aspects of Cannabinoids.","authors":"Catherine A Dennen, Kenneth Blum, Abdalla Bowirrat, Jag Khalsa, Panayotis K Thanos, David Baron, Rajendra D Badgaiyan, Ashim Gupta, Eric R Braverman, Mark S Gold","doi":"10.3390/epigenomes6030027","DOIUrl":"10.3390/epigenomes6030027","url":null,"abstract":"<p><p>Cannabis is one of the most commonly used and abused illicit drugs in the world today. The United States (US) currently has the highest annual prevalence rate of cannabis consumption in the world, 17.9% in individuals aged 12 or older, and it is on the rise. With increasing cannabis use comes the potential for an increase in abuse, and according to the Substance Abuse and Mental Health Services Administration (SAMHSA), approximately 5.1% of Americans had Cannabis Use Disorder (CUD) in 2020. Research has shown that genetics and epigenetics play a significant role in cannabis use and CUD. In fact, approximately 50-70% of liability to CUD and 40-48% of cannabis use initiation have been found to be the result of genetic factors. Cannabis usage and CUD have also been linked to an increased risk of psychiatric disorders and Reward Deficiency Syndrome (RDS) subsets like schizophrenia, depression, anxiety, and substance use disorder. Comprehension of the genetic and epigenetic aspects of cannabinoids is necessary for future research, treatment plans, and the production of pure cannabinoid compounds, which will be essential for FDA approval. In conclusion, having a better understanding of the epigenetic and genetic underpinnings of cannabis use, CUD, and the endocannabinoid system as a whole will aid in the development of effective FDA-approved treatment therapies and the advancement of personalized medicine.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9498086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33469405","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}