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Epigenomes, Volume 4, Issue 4 (December 2020) – 6 articles

Cover Story (view full-size image): Epigenomes modulate cell differentiation, maturation, and biological function, which also participate in cancer development. As a result of the epigenetic silencing of inflammatory-related genes, some tumors may not respond to immunotherapy. Moreover, tumor-associated cells also contribute to immune quiescence via epigenetic regulation. Hence, targeting specific cells with epigenetic inhibitors in combination with immunotherapy may be a potential therapeutic strategy. In this review, we summarize several clinical trials that combined epigenetic inhibitors with immunotherapy and the potential for epigenetic control of the tumor microenvironment to improve immunotherapy. View this paper

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Open AccessArticle

Methylomes in Vegans versus Pescatarians and Nonvegetarians

and

Penelope J. Duerksen-Hughes

Epigenomes 2020, 4(4), 28; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes4040028 - 11 Dec 2020

Cited by 1 | Viewed by 1129

Abstract

Epigenetic studies in animal models have demonstrated that diet affects gene regulation by altering methylation patterns. We interrogated methylomes in humans who have different sources of protein in their diet. We compared methylation of DNA isolated from buffy coat in 38 vegans, 41 pescatarians and 68 nonvegetarians. Methylation data were obtained using Infinium HumanMethylation450 arrays and analyzed using the Partek Genomic software. Differences in differentially methylated sites were small, though with the use of relaxed statistical tests we did identify diet-associated differences. To further test the validity of these observations, we performed separate and independent comparisons of the methylation differences between vegans and nonvegetarians, and between vegans and pescatarians. The detected differences were then examined to determine if they were enriched in specific pathways. Pathway analysis revealed enrichment of several specific processes, including homeobox transcription and glutamate transport. The detected differences in DNA methylation patterns between vegans, pescatarians, and nonvegetarians enabled us to identify 77 CpG sites that may be sensitive to diet and/or lifestyle, though high levels of individual-specific differences were also noted. Full article

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Open AccessReview

Combinatorial Epigenetic and Immunotherapy in Breast Cancer Management: A Literature Review

Yu-Ting Lee

Yu-Ming Chuang

and

Michael W. Y. Chan

Epigenomes 2020, 4(4), 27; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes4040027 - 04 Dec 2020

Cited by 2 | Viewed by 1006

Abstract

Breast cancer is one of the leading causes of death among cancer patients worldwide. To date, there are several drugs that have been developed for breast cancer therapy. In the 21st century, immunotherapy is considered a pioneering method for improving the management of malignancies; however, breast cancer is an exception. According to the immunoediting model, many immunosuppressive cells contribute to immunological quiescence. Therefore, there is an urgent need to enhance the therapeutic efficacy of breast cancer treatments. In the last few years, numerous combinatorial therapies involving immune checkpoint blockade have been demonstrated that effectively improve clinical outcomes in breast cancer and combining these with methods of targeting epigenetic regulators is also an innovative strategy. Nevertheless, few studies have discussed the benefits of epi-drugs in non-cancerous cells. In this review, we give a brief overview of ongoing clinical trials involving combinatorial immunotherapy with epi-drugs in breast cancer and discuss the role of epi-drugs in the tumor microenvironment, including the results of recent research. Full article

(This article belongs to the Special Issue Targeting the Epigenetic Machinery to Enhance Cancer Immunotherapy)

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Open AccessEditorial

Interplay between DNA and RNA Modifications: A Constantly Evolving Process

Annalisa Fico

Luciano Di Croce

and

Maria R. Matarazzo

Epigenomes 2020, 4(4), 26; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes4040026 - 23 Nov 2020

Viewed by 957

Abstract

The epigenome refers to the entirety of DNA methylations, histone modifications, nucleosome occupancy, and coding and non-coding RNAs (and their modifications) in different cell types [...] Full article

(This article belongs to the Special Issue Epigenome, Epitranscriptome and Single Cell Analysis in Cell Fate Choice)

Open AccessReview

Quantitative Epigenetics: A New Avenue for Crop Improvement

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Epigenomes 2020, 4(4), 25; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes4040025 - 07 Nov 2020

Cited by 3 | Viewed by 2082

Abstract

Plant breeding conventionally depends on genetic variability available in a species to improve a particular trait in the crop. However, epigenetic diversity may provide an additional tier of variation. The recent advent of epigenome technologies has elucidated the role of epigenetic variation in shaping phenotype. Furthermore, the development of epigenetic recombinant inbred lines (epi-RILs) in model species such as Arabidopsis has enabled accurate genetic analysis of epigenetic variation. Subsequently, mapping of epigenetic quantitative trait loci (epiQTL) allowed association between epialleles and phenotypic traits. Likewise, epigenome-wide association study (EWAS) and epi-genotyping by sequencing (epi-GBS) have revolutionized the field of epigenetics research in plants. Thus, quantitative epigenetics provides ample opportunities to dissect the role of epigenetic variation in trait regulation, which can be eventually utilized in crop improvement programs. Moreover, locus-specific manipulation of DNA methylation by epigenome-editing tools such as clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) can potentially facilitate epigenetic based molecular breeding of important crop plants. Full article

(This article belongs to the Special Issue Advances in Plant Epigenetics and Epigenomics)

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Open AccessArticle

Simplified MethylRAD Sequencing to Detect Changes in DNA Methylation at Enhancer Elements in Differentiating Embryonic Stem Cells

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Epigenomes 2020, 4(4), 24; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes4040024 - 01 Oct 2020

Viewed by 1697

Abstract

Differential DNA methylation is characteristic of gene regulatory regions, such as enhancers, which mostly constitute low or intermediate CpG content in their DNA sequence. Consequently, quantification of changes in DNA methylation at these sites is challenging. Given that DNA methylation across most of the mammalian genome is maintained, the use of genome-wide bisulfite sequencing to measure fractional changes in DNA methylation at specific sites is an overexertion which is both expensive and cumbersome. Here, we developed a MethylRAD technique with an improved experimental plan and bioinformatic analysis tool to examine regional DNA methylation changes in embryonic stem cells (ESCs) during differentiation. The transcriptional silencing of pluripotency genes (PpGs) during ESC differentiation is accompanied by PpG enhancer (PpGe) silencing mediated by the demethylation of H3K4me1 by LSD1. Our MethylRAD data show that in the presence of LSD1 inhibitor, a significant fraction of LSD1-bound PpGe fails to gain DNA methylation. We further show that this effect is mostly observed in PpGes with low/intermediate CpG content. Underscoring the sensitivity and accuracy of MethylRAD sequencing, our study demonstrates that this method can detect small changes in DNA methylation in regulatory regions, including those with low/intermediate CpG content, thus asserting its use as a method of choice for diagnostic purposes. Full article

(This article belongs to the Special Issue Epigenetics in Stem Cells and Their Derivatives)

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Open AccessReview

UV Radiation and Its Relation to DNA Methylation in Epidermal Cells: A Review

Naila Francis Paulo de Oliveira

Beatriz Fernandes de Souza

and

Marina de Castro Coêlho

Epigenomes 2020, 4(4), 23; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes4040023 - 30 Sep 2020

Cited by 1 | Viewed by 1240

Abstract

DNA methylation is the most studied epigenetic mark, and it can be altered by environmental factors. Among these factors, ultraviolet radiation (UV) is little explored within this context. While the relationship between UV radiation and DNA mutations is clear, little is known about the relationship between UV radiation and epimutations. The present study aimed to perform a literature review to determine the influence of artificial or natural (solar) UV radiation on the global and site-specific methylation profile of epidermal cells. A systematic review of the literature was carried out using the databases PubMed, Scopus, Cochrane, and Web of Science. Observational and intervention studies in cultured cells and animal or human models were included. Most studies showed a relationship between UV radiation and changes in the methylation profile, both global and site-specific. Hypermethylation and hypomethylation changes were detected, which varied according to the studied CpG site. In conclusion, UV radiation can alter the DNA methylation profile in epidermal cells derived from the skin. These data can be used as potential biomarkers for environmental exposure and skin diseases, in addition to being targets for treatments. On the other hand, UV radiation (phototherapy) can also be used as a tool to treat skin diseases. Thus, the data suggest that epigenetic homeostasis can be disrupted or restored by exposure to UV radiation according to the applied wavelength. Full article

(This article belongs to the Collection Epigenetic Regulation of Cellular Differentiation)

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Epigenomes, Volume 4, Issue 4 (December 2020) – 6 articles

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