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Epigenomes
Volume 3
Issue 1
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Epigenomes, Volume 3, Issue 1 (March 2019) – 7 articles

Cover Story (view full-size image): Stress-tolerant plants can allow connections to be revealed between specific epigenetic modifications and stress tolerance capacity. The MeDIP-Seq analysis of a salt-tolerant rice variety under salinity revealed a set of differentially methylated regions (DMRs) between control and stress. The DNA methylation patterns of DMRs revealed a general tendency for demethylation events under salt stress conditions. The identification of DMRs represents one step forward to uncover new players in the regulation of stress-responsive genes and new target regions with potential application to enhance plant salinity tolerance. View Paper here.
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14 pages, 1722 KiB  
Article
An Orphan CpG Island Drives Expression of a let-7 miRNA Precursor with an Important Role in Mouse Development
by Martha V. Koerner, Kashyap Chhatbar, Shaun Webb, Justyna Cholewa-Waclaw, Jim Selfridge, Dina De Sousa, Bill Skarnes, Barry Rosen, Mark Thomas, Joanna Bottomley, Ramiro Ramirez-Solis, Christopher Lelliott, David J. Adams and Adrian Bird
Epigenomes 2019, 3(1), 7; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes3010007 - 13 Mar 2019
Cited by 2 | Viewed by 4155
Abstract
Most human genes are associated with promoters embedded in non-methylated, G + C-rich CpG islands (CGIs). Not all CGIs are found at annotated promoters, however, raising the possibility that many serve as promoters for transcripts that do not code for proteins. To test [...] Read more.
Most human genes are associated with promoters embedded in non-methylated, G + C-rich CpG islands (CGIs). Not all CGIs are found at annotated promoters, however, raising the possibility that many serve as promoters for transcripts that do not code for proteins. To test this hypothesis, we searched for novel transcripts in embryonic stem cells (ESCs) that originate within orphan CGIs. Among several candidates, we detected a transcript that included three members of the let-7 micro-RNA family: Let-7a-1, let-7f-1, and let-7d. Deletion of the CGI prevented expression of the precursor RNA and depleted the included miRNAs. Mice homozygous for this mutation were sub-viable and showed growth and other defects. The results suggest that despite the identity of their seed sequences, members of the let-7 miRNA family exert distinct functions that cannot be complemented by other members. Full article
(This article belongs to the Special Issue A Commemorative Issue in Honor of Professor Denise P. Barlow: Genomic Imprinting, Epigenetics and Transcriptional Control)
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22 pages, 310 KiB  
Review
The Relevance of Gender in Tumor-Influencing Epigenetic Traits
by Victoria Sarne, Sandrina Braunmueller, Lisa Rakob and Rita Seeboeck
Epigenomes 2019, 3(1), 6; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes3010006 - 28 Jan 2019
Cited by 4 | Viewed by 4776
Abstract
Tumorigenesis as well as the molecular orchestration of cancer progression are very complex mechanisms that comprise numerous elements of influence and regulation. Today, many of the major concepts are well described and a basic understanding of a tumor’s fine-tuning is given. Throughout the [...] Read more.
Tumorigenesis as well as the molecular orchestration of cancer progression are very complex mechanisms that comprise numerous elements of influence and regulation. Today, many of the major concepts are well described and a basic understanding of a tumor’s fine-tuning is given. Throughout the last decade epigenetics has been featured in cancer research and it is now clear that the underlying mechanisms, especially DNA and histone modifications, are important regulators of carcinogenesis and tumor progression. Another key regulator, which is well known but has been neglected in scientific approaches as well as molecular diagnostics and, consequently, treatment conceptualization for a long time, is the subtle influence patient gender has on molecular processes. Naturally, this is greatly based on hormonal differences, but from an epigenetic point of view, the diverse susceptibility to stress and environmental influences is of prime interest. In this review we present the current view on which and how epigenetic modifications, emphasizing DNA methylation, regulate various tumor diseases. It is our aim to elucidate gender and epigenetics and their interconnectedness, which will contribute to understanding of the prospect molecular orchestration of cancer in individual tumors. Full article
(This article belongs to the Special Issue Biological Methylation in Development and Cancer)
19 pages, 328 KiB  
Review
Epigenomics of Pancreatic Cancer: A Critical Role for Epigenome-Wide Studies
by Rahul R. Singh, Katie M. Reindl and Rick J. Jansen
Epigenomes 2019, 3(1), 5; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes3010005 - 19 Jan 2019
Cited by 3 | Viewed by 5028
Abstract
Several challenges present themselves when discussing current approaches to the prevention or treatment of pancreatic cancer. Up to 45% of the risk of pancreatic cancer is attributed to unknown causes, making effective prevention programs difficult to design. The most common type of pancreatic [...] Read more.
Several challenges present themselves when discussing current approaches to the prevention or treatment of pancreatic cancer. Up to 45% of the risk of pancreatic cancer is attributed to unknown causes, making effective prevention programs difficult to design. The most common type of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC), is generally diagnosed at a late stage, leading to a poor prognosis and 5-year survival estimate. PDAC tumors are heterogeneous, leading to many identified cell subtypes within one patient’s primary tumor. This explains why there is a high frequency of tumors that are resistant to standard treatments, leading to high relapse rates. This review will discuss how epigenetic technologies and epigenome-wide association studies have been used to address some of these challenges and the future promises these approaches hold. Full article
(This article belongs to the Special Issue Epigenetics of Pancreatic Cancer)
13 pages, 2494 KiB  
Article
Uncovering Differentially Methylated Regions (DMRs) in a Salt-Tolerant Rice Variety under Stress: One Step towards New Regulatory Regions for Enhanced Salt Tolerance
by Liliana J. Ferreira, Mark T. A. Donoghue, Pedro Barros, Nelson J. Saibo, Ana Paula Santos and M. Margarida Oliveira
Epigenomes 2019, 3(1), 4; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes3010004 - 18 Jan 2019
Cited by 20 | Viewed by 6416
Abstract
Chromatin structure, DNA methylation, and histone modifications act in a concerted manner to influence gene expression and therefore plant phenotypes. Environmental stresses are often associated with extensive chromatin rearrangements and modifications of epigenetic levels and patterns. Stress-tolerant plants can be a good tool [...] Read more.
Chromatin structure, DNA methylation, and histone modifications act in a concerted manner to influence gene expression and therefore plant phenotypes. Environmental stresses are often associated with extensive chromatin rearrangements and modifications of epigenetic levels and patterns. Stress-tolerant plants can be a good tool to unveil potential connections between specific epigenetic modifications and stress tolerance capacity. We analyzed genome wide DNA methylation of a salt-tolerant rice variety under salinity and identified a set of differentially methylated regions (DMRs) between control and stress samples using high-throughput sequencing of DNA immunoprecipitated with the 5-methylcytosine antibody (MeDIP-Seq). The examination of DNA methylation pattern at DMRs regions revealed a general tendency for demethylation events in stress samples as compared to control. In addition, DMRs appear to influence the expression of genes located in their vicinity. We hypothesize that short regions as DMRs can shape the chromatin landscape of specific genomic regions and, therefore, may modulate the function of several genes. In this sense, the identification of DMRs represents one step towards to uncover new players in the regulation of stress-responsive genes and new target genes with potential application in enhancement of plant salinity-tolerance. Full article
(This article belongs to the Special Issue Plant Epigenetics)
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20 pages, 4930 KiB  
Article
Biotic Stress-Induced Priming and De-Priming of Transcriptional Memory in Arabidopsis and Apple
by Kay Gully, Jean-Marc Celton, Alexandre Degrave, Sandra Pelletier, Marie-Noelle Brisset and Etienne Bucher
Epigenomes 2019, 3(1), 3; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes3010003 - 14 Jan 2019
Cited by 12 | Viewed by 6990
Abstract
Under natural growth conditions, plants experience various and repetitive biotic and abiotic stresses. Salicylic acid (SA) is a key phytohormone involved in the response to biotic challenges. Application of synthetic SA analogues can efficiently prime defense responses, and leads to improved pathogen resistance. [...] Read more.
Under natural growth conditions, plants experience various and repetitive biotic and abiotic stresses. Salicylic acid (SA) is a key phytohormone involved in the response to biotic challenges. Application of synthetic SA analogues can efficiently prime defense responses, and leads to improved pathogen resistance. Because SA analogues can result in long-term priming and memory, we identified genes for which expression was affected by the SA analogue and explored the role of DNA methylation in this memorization process. We show that treatments with an SA analogue can lead to long-term transcriptional memory of particular genes in Arabidopsis. We found that subsequent challenging of such plants with a bacterial elicitor reverted this transcriptional memory, bringing their expression back to the original pre-treatment level. We also made very similar observations in apple (Malus domestica), suggesting that this expression pattern is highly conserved in plants. Finally, we found a potential role for DNA methylation in the observed transcriptional memory behavior. We show that plants defective in DNA methylation pathways displayed a different memory behavior. Our work improves our understanding of the role of transcriptional memory in priming, and has important implication concerning the application of SA analogues in agricultural settings. Full article
(This article belongs to the Special Issue Plant Epigenetics)
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1 pages, 280 KiB  
Editorial
Acknowledgement to Reviewers of Epigenomes in 2018
by Epigenomes Editorial Office
Epigenomes 2019, 3(1), 2; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes3010002 - 11 Jan 2019
Viewed by 2477
Abstract
Rigorous peer-review is the corner-stone of high-quality academic publishing [...] Full article
21 pages, 1308 KiB  
Review
Epigenetic Regulation of EMT (Epithelial to Mesenchymal Transition) and Tumor Aggressiveness: A View on Paradoxical Roles of KDM6B and EZH2
by Camille Lachat, Michaël Boyer-Guittaut, Paul Peixoto and Eric Hervouet
Epigenomes 2019, 3(1), 1; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes3010001 - 20 Dec 2018
Cited by 11 | Viewed by 6092
Abstract
EMT (epithelial to mesenchymal transition) is a plastic phenomenon involved in metastasis formation. Its plasticity is conferred in a great part by its epigenetic regulation. It has been reported that the trimethylation of lysine 27 histone H3 (H3K27me3) was a master regulator of [...] Read more.
EMT (epithelial to mesenchymal transition) is a plastic phenomenon involved in metastasis formation. Its plasticity is conferred in a great part by its epigenetic regulation. It has been reported that the trimethylation of lysine 27 histone H3 (H3K27me3) was a master regulator of EMT through two antagonist enzymes that regulate this mark, the methyltransferase EZH2 (enhancer of zeste homolog 2) and the lysine demethylase KDM6B (lysine femethylase 6B). Here we report that EZH2 and KDM6B are overexpressed in numerous cancers and involved in the aggressive phenotype and EMT in various cell lines by regulating a specific subset of genes. The first paradoxical role of these enzymes is that they are antagonistic, but both involved in cancer aggressiveness and EMT. The second paradoxical role of EZH2 and KDM6B during EMT and cancer aggressiveness is that they are also inactivated or under-expressed in some cancer types and linked to epithelial phenotypes in other cancer cell lines. We also report that new cancer therapeutic strategies are targeting KDM6B and EZH2, but the specificity of these treatments may be increased by learning more about the mechanisms of action of these enzymes and their specific partners or target genes in different cancer types. Full article
(This article belongs to the Special Issue Biological Methylation in Development and Cancer 2.0)
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