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":null,"pages":null},"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}
EpigenomesPub Date : 2022-08-22DOI: 10.3390/epigenomes6030025
Itzel Alejandra Hernández-Romero, Victor Julian Valdes
{"title":"<i>De Novo</i> Polycomb Recruitment and Repressive Domain Formation.","authors":"Itzel Alejandra Hernández-Romero, Victor Julian Valdes","doi":"10.3390/epigenomes6030025","DOIUrl":"10.3390/epigenomes6030025","url":null,"abstract":"<p><p>Every cell of an organism shares the same genome; even so, each cellular lineage owns a different transcriptome and proteome. The Polycomb group proteins (PcG) are essential regulators of gene repression patterning during development and homeostasis. However, it is unknown how the repressive complexes, PRC1 and PRC2, identify their targets and elicit new Polycomb domains during cell differentiation. Classical recruitment models consider the pre-existence of repressive histone marks; still, <i>de novo</i> target binding overcomes the absence of both H3K27me3 and H2AK119ub. The CpG islands (CGIs), non-core proteins, and RNA molecules are involved in Polycomb recruitment. Nonetheless, it is unclear how <i>de novo</i> targets are identified depending on the physiological context and developmental stage and which are the leading players stabilizing Polycomb complexes at domain nucleation sites. Here, we examine the features of <i>de novo</i> sites and the accessory elements bridging its recruitment and discuss the first steps of Polycomb domain formation and transcriptional regulation, comprehended by the experimental reconstruction of the repressive domains through time-resolved genomic analyses in mammals.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9397058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40649122","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":null,"pages":null},"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":null,"pages":null},"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 : 2022-08-02DOI: 10.3390/epigenomes6030022
Shoko Sato, Mariko Dacher, Hitoshi Kurumizaka
{"title":"Nucleosome Structures Built from Highly Divergent Histones: Parasites and Giant DNA Viruses.","authors":"Shoko Sato, Mariko Dacher, Hitoshi Kurumizaka","doi":"10.3390/epigenomes6030022","DOIUrl":"10.3390/epigenomes6030022","url":null,"abstract":"<p><p>In eukaryotes, genomic DNA is bound with histone proteins and packaged into chromatin. The nucleosome, a fundamental unit of chromatin, regulates the accessibility of DNA to enzymes involved in gene regulation. During the past few years, structural analyses of chromatin architectures have been limited to evolutionarily related organisms. The amino acid sequences of histone proteins are highly conserved from humans to yeasts, but are divergent in the deeply branching protozoan groups, including human parasites that are directly related to human health. Certain large DNA viruses, as well as archaeal organisms, contain distant homologs of eukaryotic histone proteins. The divergent sequences give rise to unique and distinct nucleosome architectures, although the fundamental principles of histone folding and DNA contact are highly conserved. In this article, we review the structures and biophysical properties of nucleosomes containing histones from the human parasites <i>Giardia lamblia</i> and <i>Leishmania major</i>, and histone-like proteins from the <i>Marseilleviridae</i> amoeba virus family. The presented data confirm the sharing of the overall DNA compaction system among evolutionally distant species and clarify the deviations from the species-specific nature of the nucleosome.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40649118","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 : 2022-07-27DOI: 10.3390/epigenomes6030021
Beatriz Martinez-Delgado, Maria J Barrero
{"title":"Epigenomic Approaches for the Diagnosis of Rare Diseases.","authors":"Beatriz Martinez-Delgado, Maria J Barrero","doi":"10.3390/epigenomes6030021","DOIUrl":"10.3390/epigenomes6030021","url":null,"abstract":"<p><p>Rare diseases affect more than 300 million people worldwide. Diagnosing rare diseases is a major challenge as they have different causes and etiologies. Careful assessment of clinical symptoms often leads to the testing of the most common genetic alterations that could explain the disease. Patients with negative results for these tests frequently undergo whole exome or genome sequencing, leading to the identification of the molecular cause of the disease in 50% of patients at best. Therefore, a significant proportion of patients remain undiagnosed after sequencing their genome. Recently, approaches based on functional aspects of the genome, including transcriptomics and epigenomics, are beginning to emerge. Here, we will review these approaches, including studies that have successfully provided diagnoses for complex undiagnosed cases.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9397041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40633179","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/epigenomes6030020
Keishi Shintomi
{"title":"Making Mitotic Chromosomes in a Test Tube.","authors":"Keishi Shintomi","doi":"10.3390/epigenomes6030020","DOIUrl":"10.3390/epigenomes6030020","url":null,"abstract":"<p><p>Mitotic chromosome assembly is an essential preparatory step for accurate transmission of the genome during cell division. During the past decades, biochemical approaches have uncovered the molecular basis of mitotic chromosomes. For example, by using cell-free assays of frog egg extracts, the condensin I complex central for the chromosome assembly process was first identified, and its functions have been intensively studied. A list of chromosome-associated proteins has been almost completed, and it is now possible to reconstitute structures resembling mitotic chromosomes with a limited number of purified factors. In this review, I introduce how far we have come in understanding the mechanism of chromosome assembly using cell-free assays and reconstitution assays, and I discuss their potential applications to solve open questions.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40633947","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":null,"pages":null},"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":null,"pages":null},"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}
EpigenomesPub Date : 2022-07-12DOI: 10.3390/epigenomes6030018
Takashi Umehara
{"title":"Epidrugs: Toward Understanding and Treating Diverse Diseases.","authors":"Takashi Umehara","doi":"10.3390/epigenomes6030018","DOIUrl":"https://doi.org/10.3390/epigenomes6030018","url":null,"abstract":"<p><p>Epigenomic modifications are unique in the type and amount of chemical modification at each chromosomal location, can vary from cell to cell, and can be externally modulated by small molecules. In recent years, genome-wide epigenomic modifications have been revealed, and rapid progress has been made in the identification of proteins responsible for epigenomic modifications and in the development of compounds that regulate them. This Special Issue on \"Epidrugs: Toward Understanding and Treating Diverse Diseases\" aims to provide insights into various aspects of the biology and development of epigenome-regulating compounds.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40647021","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}