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Epigenomes, Volume 3, Issue 2 (June 2019) – 5 articles

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Cover Story (view full-size image) The brain is highly dependent on the environment to function, promoting unique DNA methylation [...] Read more.
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Open AccessReview
Polycomb Assemblies Multitask to Regulate Transcription
Epigenomes 2019, 3(2), 12; https://doi.org/10.3390/epigenomes3020012 - 20 Jun 2019
Cited by 2 | Viewed by 1370
Abstract
The Polycomb system is made of an evolutionary ancient group of proteins, present throughout plants and animals. Known initially from developmental studies with the fly Drosophila melanogaster, they were associated with stable sustainment of gene repression and maintenance of cell identity. Acting [...] Read more.
The Polycomb system is made of an evolutionary ancient group of proteins, present throughout plants and animals. Known initially from developmental studies with the fly Drosophila melanogaster, they were associated with stable sustainment of gene repression and maintenance of cell identity. Acting as multiprotein assemblies with an ability to modify chromatin, through chemical additions to histones and organization of topological domains, they have been involved subsequently in control of developmental transitions and in cell homeostasis. Recent work has unveiled an association of Polycomb components with transcriptionally active loci and the promotion of gene expression, in clear contrast with conventional recognition as repressors. Focusing on mammalian models, I review here advances concerning roles in transcriptional control. Among new findings highlighted is the regulation of their catalytic properties, recruiting to targets, and activities in chromatin organization and compartmentalization. The need for a more integrated approach to the study of the Polycomb system, given its fundamental complexity and its adaptation to cell context, is discussed. Full article
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Open AccessArticle
Disruption of Broad Epigenetic Domains in PDAC Cells by HAT Inhibitors
Epigenomes 2019, 3(2), 11; https://doi.org/10.3390/epigenomes3020011 - 02 Jun 2019
Cited by 2 | Viewed by 1239
Abstract
The spreading of epigenetic domains has emerged as a distinguishing epigenomic phenotype for diverse cell types. In particular, clusters of H3K27ac- and H3K4me3-marked elements, referred to as super-enhancers, and broad H3K4me3 domains, respectively, have been linked to cell identity and disease states. Here, [...] Read more.
The spreading of epigenetic domains has emerged as a distinguishing epigenomic phenotype for diverse cell types. In particular, clusters of H3K27ac- and H3K4me3-marked elements, referred to as super-enhancers, and broad H3K4me3 domains, respectively, have been linked to cell identity and disease states. Here, we characterized the broad domains from different pancreatic ductal adenocarcinoma (PDAC) cell lines that represent distinct histological grades. Our integrative genomic analysis found that human derived cell line models for distinct PDAC grades exhibit characteristic broad epigenetic features associated with gene expression patterns that are predictive of patient prognosis and provide insight into pancreatic cancer cell identity. In particular, we find that genes marked by overlapping Low-Grade broad domains correspond to an epithelial phenotype and hold potential as markers for patient stratification. We further utilize ChIP-seq to compare the effects of histone acetyltransferase (HAT) inhibitors to detect global changes in histone acetylation and methylation levels. We found that HAT inhibitors impact certain broad domains of pancreatic cancer cells. Overall, our results reveal potential roles for broad domains in cells from distinct PDAC grades and demonstrate the plasticity of particular broad epigenomic domains to epigenetic inhibitors. Full article
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Open AccessArticle
Integrating Signals from Sperm Methylome Analysis and Genome-Wide Association Study for a Better Understanding of Male Fertility in Cattle
Epigenomes 2019, 3(2), 10; https://doi.org/10.3390/epigenomes3020010 - 16 May 2019
Cited by 4 | Viewed by 1227
Abstract
Decreased male fertility is a big concern in both human society and the livestock industry. Sperm DNA methylation is commonly believed to be associated with male fertility. However, due to the lack of accurate male fertility records (i.e., limited mating times), few studies [...] Read more.
Decreased male fertility is a big concern in both human society and the livestock industry. Sperm DNA methylation is commonly believed to be associated with male fertility. However, due to the lack of accurate male fertility records (i.e., limited mating times), few studies have investigated the comprehensive impacts of sperm DNA methylation on male fertility in mammals. In this study, we generated 10 sperm DNA methylomes and performed a preliminary correlation analysis between signals from sperm DNA methylation and signals from large-scale (n = 27,214) genome-wide association studies (GWAS) of 35 complex traits (including 12 male fertility-related traits). We detected genomic regions, which experienced DNA methylation alterations in sperm and were associated with aging and extreme fertility phenotypes (e.g., sire-conception rate or SCR). In dynamic hypomethylated regions (HMRs) and partially methylated domains (PMDs), we found genes (e.g., HOX gene clusters and microRNAs) that were involved in the embryonic development. We demonstrated that genomic regions, which gained rather than lost methylations during aging, and in animals with low SCR were significantly and selectively enriched for GWAS signals of male fertility traits. Our study discovered 16 genes as the potential candidate markers for male fertility, including SAMD5 and PDE5A. Collectively, this initial effort supported a hypothesis that sperm DNA methylation may contribute to male fertility in cattle and revealed the usefulness of functional annotations in enhancing biological interpretation and genomic prediction for complex traits and diseases. Full article
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Open AccessEditorial
5-Methylcytosine and 5-Hydroxymethylcytosine Signatures Underlying Pediatric Cancers
Epigenomes 2019, 3(2), 9; https://doi.org/10.3390/epigenomes3020009 - 09 May 2019
Cited by 1 | Viewed by 1227
Abstract
In addition to the genetic variations, recent evidence has shown that DNA methylation of both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) underlies the pathogenesis of pediatric cancer. Given the high mortality rate, there is an urgent need to study the mechanisms contributing to the [...] Read more.
In addition to the genetic variations, recent evidence has shown that DNA methylation of both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) underlies the pathogenesis of pediatric cancer. Given the high mortality rate, there is an urgent need to study the mechanisms contributing to the pathogenicity of pediatric cancer. Over the past decades, next-generation sequencing (NGS) has enabled us to perform genome-wide screening to study the complex regulatory mechanisms of 5mC and 5hmC underlying pediatric tumorigenesis. To shed light on recent developments on pediatric cancer predisposition and tumor progression, here we discuss the role of both genome-wide and locus-specific dysregulation of 5mC and 5hmC in hematopoiesis malignancy and neuroblastoma, the most common types of pediatric cancer, together with their therapeutic potential. Full article
(This article belongs to the Special Issue Biological Methylation in Development and Cancer)
Open AccessBrief Report
Global DNA Methylation in the Limbic System of Cattle
Epigenomes 2019, 3(2), 8; https://doi.org/10.3390/epigenomes3020008 - 05 May 2019
Cited by 1 | Viewed by 1565
Abstract
To elucidate the extent to which DNA methylation varies across multiple tissues in the brain and between animals, we have quantified global DNA methylation in tissues comprising the limbic system for six Red Angus x Simmental steers. Global DNA methylation was measured in [...] Read more.
To elucidate the extent to which DNA methylation varies across multiple tissues in the brain and between animals, we have quantified global DNA methylation in tissues comprising the limbic system for six Red Angus x Simmental steers. Global DNA methylation was measured in nine regions of the bovine brain: amygdala, the bed nucleus of the stria terminalis, cingulate gyrus, dorsal raphe, hippocampus, hypothalamus, nucleus accumbens, periaqueductal gray and prefrontal cortex. DNA methylation varies among animals for each tissue type and varies among tissue types for each animal. The highest amounts of DNA methylation were found in the amygdala, cingulate gyrus and dorsal raphe, while the bed nucleus of the stria terminalis, nucleus accumbens and periaqueductal gray had the lowest amounts of DNA methylation. A heatmap sorted by k-means clustering was generated to graphically display percent DNA methylation in relation to tissue type and animal number. This is the first study to report measures of DNA methylation in the limbic system of the bovine brain and can be used to inform the cattle genomics community of expected variation in cattle brain methylation. Full article
(This article belongs to the Special Issue Epigenetics of the Nervous System 2.0)
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