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Epigenomes, Volume 6, Issue 1 (March 2022) – 10 articles

Cover Story (view full-size image): Title story: Polycomb Repressive Complex 2 (PRC2) represents a group an evolutionarily conserved multi-subunit complexes that repress gene transcription by trimethylating lysine 27 on histone 3 (H3K27me3). In animals and plants, PRC2 activity is crucial for cell identity specification and developmental phase transitions. PRC2 complexes have recently been identified in a variety of eukaryotic supergroups, showing that the complex and its function are conserved. This review provides an overview of current knowledge about PRC2 core composition and PRC2-mediated repression across major eukaryotic supergroups, with a focus on the green lineage, as well as emerging questions and research directions for future Polycomb repression and evolution studies. View this paper
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Review
SWI/SNF Chromatin Remodeling Enzymes in Melanoma
Epigenomes 2022, 6(1), 10; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes6010010 - 18 Mar 2022
Viewed by 1147
Abstract
Melanoma is an aggressive malignancy that arises from the transformation of melanocytes on the skin, mucosal membranes, and uvea of the eye. SWI/SNF chromatin remodeling enzymes are multi-subunit complexes that play important roles in the development of the melanocyte lineage and in the [...] Read more.
Melanoma is an aggressive malignancy that arises from the transformation of melanocytes on the skin, mucosal membranes, and uvea of the eye. SWI/SNF chromatin remodeling enzymes are multi-subunit complexes that play important roles in the development of the melanocyte lineage and in the response to ultraviolet radiation, a key environmental risk factor for developing cutaneous melanoma. Exome sequencing has revealed frequent loss of function mutations in genes encoding SWI/SNF subunits in melanoma. However, some SWI/SNF subunits have also been demonstrated to have pro-tumorigenic roles in melanoma and to affect sensitivity to therapeutics. This review summarizes studies that have implicated SWI/SNF components in melanomagenesis and have evaluated how SWI/SNF subunits modulate the response to current therapeutics. Full article
(This article belongs to the Collection Epigenetics of Melanoma)
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Review
Genetic and Epigenetic Inheritance at Telomeres
Epigenomes 2022, 6(1), 9; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes6010009 - 16 Mar 2022
Viewed by 1217
Abstract
Transgenerational inheritance can occur at telomeres in distinct contexts. Deficiency for telomerase or telomere-binding proteins in germ cells can result in shortened or lengthened chromosome termini that are transmitted to progeny. In human families, altered telomere lengths can result in stem cell dysfunction [...] Read more.
Transgenerational inheritance can occur at telomeres in distinct contexts. Deficiency for telomerase or telomere-binding proteins in germ cells can result in shortened or lengthened chromosome termini that are transmitted to progeny. In human families, altered telomere lengths can result in stem cell dysfunction or tumor development. Genetic inheritance of altered telomeres as well as mutations that alter telomeres can result in progressive telomere length changes over multiple generations. Telomeres of yeast can modulate the epigenetic state of subtelomeric genes in a manner that is mitotically heritable, and the effects of telomeres on subtelomeric gene expression may be relevant to senescence or other human adult-onset disorders. Recently, two novel epigenetic states were shown to occur at C. elegans telomeres, where very low or high levels of telomeric protein foci can be inherited for multiple generations through a process that is regulated by histone methylation.Together, these observations illustrate that information relevant to telomere biology can be inherited via genetic and epigenetic mechanisms, although the broad impact of epigenetic inheritance to human biology remains unclear. Full article
(This article belongs to the Special Issue Transgenerational Epigenetic Inheritance)
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Review
The Importance of Networking: Plant Polycomb Repressive Complex 2 and Its Interactors
Epigenomes 2022, 6(1), 8; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes6010008 - 03 Mar 2022
Viewed by 1444
Abstract
Polycomb Repressive Complex 2 (PRC2) is arguably the best-known plant complex of the Polycomb Group (PcG) pathway, formed by a group of proteins that epigenetically represses gene expression. PRC2-mediated deposition of H3K27me3 has amply been studied in Arabidopsis and, more recently, data from [...] Read more.
Polycomb Repressive Complex 2 (PRC2) is arguably the best-known plant complex of the Polycomb Group (PcG) pathway, formed by a group of proteins that epigenetically represses gene expression. PRC2-mediated deposition of H3K27me3 has amply been studied in Arabidopsis and, more recently, data from other plant model species has also been published, allowing for an increasing knowledge of PRC2 activities and target genes. How PRC2 molecular functions are regulated and how PRC2 is recruited to discrete chromatin regions are questions that have brought more attention in recent years. A mechanism to modulate PRC2-mediated activity is through its interaction with other protein partners or accessory proteins. Current evidence for PRC2 interactors has demonstrated the complexity of its protein network and how far we are from fully understanding the impact of these interactions on the activities of PRC2 core subunits and on the formation of new PRC2 versions. This review presents a list of PRC2 interactors, emphasizing their mechanistic action upon PRC2 functions and their effects on transcriptional regulation. Full article
(This article belongs to the Special Issue Mechanisms of Plant Epigenome Dynamics)
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Communication
Methylation Status of Exon IV of the Brain-Derived Neurotrophic Factor (BDNF)-Encoding Gene in Patients with Non-Diabetic Hyperglycaemia (NDH) before and after a Lifestyle Intervention
Epigenomes 2022, 6(1), 7; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes6010007 - 18 Feb 2022
Viewed by 1056
Abstract
BDNF signalling in hypothalamic neuronal circuits is thought to regulate mammalian food intake. In light of this, we investigated how a lifestyle intervention influenced serum levels and DNA methylation of BDNF gene in fat tissue and buffy coat of NDH individuals. In total, [...] Read more.
BDNF signalling in hypothalamic neuronal circuits is thought to regulate mammalian food intake. In light of this, we investigated how a lifestyle intervention influenced serum levels and DNA methylation of BDNF gene in fat tissue and buffy coat of NDH individuals. In total, 20 participants underwent anthropometric measurements/fasting blood tests and adipose tissue biopsy pre-/post-lifestyle (6 months) intervention. DNA was extracted from adipose tissue and buffy coat, bisulphite converted, and pyrosequencing was used to determine methylation levels in exon IV of the BDNF gene. RNA was extracted from buffy coat for gene expression analysis and serum BDNF levels were measured by ELISA. No differences were found in BDNF serum levels, but buffy coat mean BDNF gene methylation decreased post-intervention. There were correlations between BDNF serum levels and/or methylation and cardiometabolic markers. (i) Pre-intervention: for BDNF methylation, we found positive correlations between mean methylation in fat tissue and waist-hip ratio, and negative correlations between mean methylation in buffy coat and weight. (ii) Post-intervention: we found correlations between BDNF mean methylation in buffy coat and HbA1c, BDNF methylation in buffy coat and circulating IGFBP-2, and BDNF serum and insulin. Higher BDNF % methylation levels are known to reduce BNDF expression. The fall in buffy coat mean BDNF methylation plus the association between lower BDNF methylation (so potentially higher BDNF) and higher HbA1c and serum IGFBP-2 (as a marker of insulin sensitivity) and between lower serum BDNF and higher circulating insulin are evidence for the degree of BDNF gene methylation being implicated in insulinisation and glucose homeostasis, particularly after lifestyle change in NDH individuals. Full article
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Review
Opportunities for Early Cancer Detection: The Rise of ctDNA Methylation-Based Pan-Cancer Screening Technologies
Epigenomes 2022, 6(1), 6; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes6010006 - 04 Feb 2022
Viewed by 1906
Abstract
The efficiency of conventional screening programs to identify early-stage malignancies can be limited by the low number of cancers recommended for screening as well as the high cumulative false-positive rate, and associated iatrogenic burden, resulting from repeated multimodal testing. The opportunity to use [...] Read more.
The efficiency of conventional screening programs to identify early-stage malignancies can be limited by the low number of cancers recommended for screening as well as the high cumulative false-positive rate, and associated iatrogenic burden, resulting from repeated multimodal testing. The opportunity to use minimally invasive liquid biopsy testing to screen asymptomatic individuals at-risk for multiple cancers simultaneously could benefit from the aggregated diseases prevalence and a fixed specificity. Increasing both latter parameters is paramount to mediate high positive predictive value—a useful metric to evaluate a screening test accuracy and its potential harm-benefit. Thus, the use of a single test for multi-cancer early detection (stMCED) has emerged as an appealing strategy for increasing early cancer detection rate efficiency and benefit population health. A recent flurry of these stMCED technologies have been reported for clinical potential; however, their development is facing unique challenges to effectively improve clinical cost–benefit. One promising avenue is the analysis of circulating tumour DNA (ctDNA) for detecting DNA methylation biomarker fingerprints of malignancies—a hallmark of disease aetiology and progression holding the potential to be tissue- and cancer-type specific. Utilizing panels of epigenetic biomarkers could potentially help to detect earlier stages of malignancies as well as identify a tumour of origin from blood testing, useful information for follow-up clinical decision making and subsequent patient care improvement. Overall, this review collates the latest and most promising stMCED methodologies, summarizes their clinical performances, and discusses the specific requirements multi-cancer tests should meet to be successfully implemented into screening guidelines. Full article
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Editorial
Acknowledgment to Reviewers of Epigenomes in 2021
Epigenomes 2022, 6(1), 5; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes6010005 - 26 Jan 2022
Viewed by 963
Abstract
Rigorous peer-reviews are the basis of high-quality academic publishing [...] Full article
Review
Biochemical Principles in Prion-Based Inheritance
Epigenomes 2022, 6(1), 4; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes6010004 - 25 Jan 2022
Viewed by 1408
Abstract
Prions are proteins that can stably fold into alternative structures that frequently alter their activities. They can self-template their alternate structures and are inherited across cell divisions and generations. While they have been studied for more than four decades, their enigmatic nature has [...] Read more.
Prions are proteins that can stably fold into alternative structures that frequently alter their activities. They can self-template their alternate structures and are inherited across cell divisions and generations. While they have been studied for more than four decades, their enigmatic nature has limited their discovery. In the last decade, we have learned just how widespread they are in nature, the many beneficial phenotypes that they confer, while also learning more about their structures and modes of inheritance. Here, we provide a brief review of the biochemical principles of prion proteins, including their sequences, characteristics and structures, and what is known about how they self-template, citing examples from multiple organisms. Prion-based inheritance is the most understudied segment of epigenetics. Here, we lay a biochemical foundation and share a framework for how to define these molecules, as new examples are unearthed throughout nature. Full article
(This article belongs to the Special Issue Transgenerational Epigenetic Inheritance)
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Review
Polycomb Repressive Complex 2 in Eukaryotes—An Evolutionary Perspective
Epigenomes 2022, 6(1), 3; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes6010003 - 17 Jan 2022
Cited by 2 | Viewed by 1702
Abstract
Polycomb repressive complex 2 (PRC2) represents a group of evolutionarily conserved multi-subunit complexes that repress gene transcription by introducing trimethylation of lysine 27 on histone 3 (H3K27me3). PRC2 activity is of key importance for cell identity specification and developmental phase transitions in animals [...] Read more.
Polycomb repressive complex 2 (PRC2) represents a group of evolutionarily conserved multi-subunit complexes that repress gene transcription by introducing trimethylation of lysine 27 on histone 3 (H3K27me3). PRC2 activity is of key importance for cell identity specification and developmental phase transitions in animals and plants. The composition, biochemistry, and developmental function of PRC2 in animal and flowering plant model species are relatively well described. Recent evidence demonstrates the presence of PRC2 complexes in various eukaryotic supergroups, suggesting conservation of the complex and its function. Here, we provide an overview of the current understanding of PRC2-mediated repression in different representatives of eukaryotic supergroups with a focus on the green lineage. By comparison of PRC2 in different eukaryotes, we highlight the possible common and diverged features suggesting evolutionary implications and outline emerging questions and directions for future research of polycomb repression and its evolution. Full article
(This article belongs to the Special Issue Mechanisms of Plant Epigenome Dynamics)
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Editorial
Chromatin Unlimited: An Evolutionary View of Chromatin
Epigenomes 2022, 6(1), 2; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes6010002 - 02 Jan 2022
Viewed by 984
Abstract
Chromatin is a fundamental and highly conserved structure that carries genetic and epigenetic information in eukaryotic cells [...] Full article
(This article belongs to the Special Issue Chromatin Unlimited)
Article
Epigenetics of Mitochondria-Associated Genes in Striated Muscle
Epigenomes 2022, 6(1), 1; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes6010001 - 22 Dec 2021
Cited by 1 | Viewed by 1582
Abstract
Striated muscle has especially large energy demands. We identified 97 genes preferentially expressed in skeletal muscle and heart, but not in aorta, and found significant enrichment for mitochondrial associations among them. We compared the epigenomic and transcriptomic profiles of the 27 genes associated [...] Read more.
Striated muscle has especially large energy demands. We identified 97 genes preferentially expressed in skeletal muscle and heart, but not in aorta, and found significant enrichment for mitochondrial associations among them. We compared the epigenomic and transcriptomic profiles of the 27 genes associated with striated muscle and mitochondria. Many showed strong correlations between their tissue-specific transcription levels, and their tissue-specific promoter, enhancer, or open chromatin as well as their DNA hypomethylation. Their striated muscle-specific enhancer chromatin was inside, upstream, or downstream of the gene, throughout much of the gene as a super-enhancer (CKMT2, SLC25A4, and ACO2), or even overlapping a neighboring gene (COX6A2, COX7A1, and COQ10A). Surprisingly, the 3′ end of the 1.38 Mb PRKN (PARK2) gene (involved in mitophagy and linked to juvenile Parkinson’s disease) displayed skeletal muscle/myoblast-specific enhancer chromatin, a myoblast-specific antisense RNA, as well as brain-specific enhancer chromatin. We also found novel tissue-specific RNAs in brain and embryonic stem cells within PPARGC1A (PGC-1α), which encodes a master transcriptional coregulator for mitochondrial formation and metabolism. The tissue specificity of this gene’s four alternative promoters, including a muscle-associated promoter, correlated with nearby enhancer chromatin and open chromatin. Our in-depth epigenetic examination of these genes revealed previously undescribed tissue-specific enhancer chromatin, intragenic promoters, regions of DNA hypomethylation, and intragenic noncoding RNAs that give new insights into transcription control for this medically important set of genes. Full article
(This article belongs to the Special Issue Epigenetics of Striated Muscle)
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