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Epigenomes, Volume 6, Issue 3 (September 2022) – 7 articles

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Review
Nucleosome Structures Built from Highly Divergent Histones: Parasites and Giant DNA Viruses
Epigenomes 2022, 6(3), 22; https://doi.org/10.3390/epigenomes6030022 - 02 Aug 2022
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Abstract
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 [...] Read more.
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 Giardia lamblia and Leishmania major, and histone-like proteins from the Marseilleviridae 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. Full article
(This article belongs to the Special Issue Chromatin Unlimited)
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Review
Epigenomic Approaches for the Diagnosis of Rare Diseases
Epigenomes 2022, 6(3), 21; https://doi.org/10.3390/epigenomes6030021 - 27 Jul 2022
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Abstract
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 [...] Read more.
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. Full article
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Review
Making Mitotic Chromosomes in a Test Tube
Epigenomes 2022, 6(3), 20; https://doi.org/10.3390/epigenomes6030020 - 20 Jul 2022
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Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Chromatin Unlimited)
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Conference Report
Clinical Epigenetics on the Baltic Coast
Epigenomes 2022, 6(3), 19; https://doi.org/10.3390/epigenomes6030019 - 20 Jul 2022
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Abstract
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 [...] Read more.
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. Full article
Editorial
Epidrugs: Toward Understanding and Treating Diverse Diseases
Epigenomes 2022, 6(3), 18; https://doi.org/10.3390/epigenomes6030018 - 12 Jul 2022
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Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Epidrugs: Toward Understanding and Treating Diverse Diseases)
Article
DNA Hypomethylation May Contribute to Metabolic Recovery of Frozen Wood Frog Brains
Epigenomes 2022, 6(3), 17; https://doi.org/10.3390/epigenomes6030017 - 12 Jul 2022
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Abstract
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 [...] Read more.
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. Full article
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Communication
Global m6A RNA Methylation in SARS-CoV-2 Positive Nasopharyngeal Samples in a Mexican Population: A First Approximation Study
Epigenomes 2022, 6(3), 16; https://doi.org/10.3390/epigenomes6030016 - 29 Jun 2022
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Abstract
The Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the causal agent of COVID-19 (Coronavirus Disease-19). Both mutation and/or recombination events in the SARS-CoV-2 genome have resulted in variants that differ in transmissibility and severity. Furthermore, RNA methylation of the N6 position of adenosine (m6A) [...] Read more.
The Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the causal agent of COVID-19 (Coronavirus Disease-19). Both mutation and/or recombination events in the SARS-CoV-2 genome have resulted in variants that differ in transmissibility and severity. Furthermore, RNA methylation of the N6 position of adenosine (m6A) is known to be altered in cells infected with SARS-CoV-2. However, it is not known whether this epitranscriptomic modification differs across individuals dependent on the presence of infection with distinct SARS-CoV-2 variants, the viral load, or the vaccination status. To address this issue, we selected RNAs (n = 60) from SARS-CoV-2 sequenced nasopharyngeal samples (n = 404) of 30- to 60-year-old outpatients or hospitalized individuals from the city of Mazatlán (Mexico) between February 2021 and March 2022. Control samples were non-infected individuals (n = 10). SARS-CoV-2 was determined with real-time PCR, viral variants were determined with sequencing, and global m6A levels were determined by using a competitive immunoassay method. We identified variants of concern (VOC; alpha, gamma, delta, omicron), the variant of interest (VOI; epsilon), and the lineage B.1.1.519. Global m6A methylation differed significantly across viral variants (p = 3.2 × 10−7). In particular, we found that m6A levels were significantly lower in the VOC delta- and omicron-positive individuals compared to non-infected individuals (p = 2.541236 × 10−2 and 1.134411 × 10−4, respectively). However, we uncovered no significant correlation between global m6A levels and viral nucleocapsid (N) gene expression or age. Furthermore, individuals with complete vaccination schemes showed significantly lower m6A levels than unvaccinated individuals (p = 2.6 × 10−4), and differences in methylation levels across variants in unvaccinated individuals were significant (p = 3.068 × 10−3). These preliminary results suggest that SARS-CoV-2 variants show differences in global m6A levels. Full article
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