'; ?> geneimprint : Hot off the Press http://www.geneimprint.com/site/hot-off-the-press Daily listing of the most recent articles in epigenetics and imprinting, collected from the PubMed database. en-us Thu, 20 Jun 2019 10:07:17 EDT Thu, 20 Jun 2019 10:07:17 EDT jirtle@radonc.duke.edu james001@jirtle.com Human monocyte-to-macrophage differentiation involves highly localized gain and loss of DNA methylation at transcription factor binding sites. Dekkers KF, Neele AE, Jukema JW, Heijmans BT, de Winther MPJ
Epigenetics Chromatin (Jun 2019)

Macrophages and their precursors monocytes play a key role in inflammation and chronic inflammatory disorders. Monocyte-to-macrophage differentiation and activation programs are accompanied by significant epigenetic remodeling where DNA methylation associates with cell identity. Here we show that DNA methylation changes characteristic for monocyte-to-macrophage differentiation occur at transcription factor binding sites, and, in contrast to what was previously described, are generally highly localized and encompass both losses and gains of DNA methylation.]]>
Wed, 31 Dec 1969 19:00:00 EST
The Role of Environmental Exposures and the Epigenome in Health and Disease. Perera BPU, Faulk C, Svoboda LK, Goodrich JM, Dolinoy DC
Environ Mol Mutagen (Jun 2019)

The genetic material of every organism exists within the context of regulatory networks that govern gene expression, collectively called the epigenome. Epigenetics has taken center stage in the study of diseases such as cancer and diabetes, but its integration into the field of environmental health is still emerging. As the Environmental Mutagenesis and Genomics Society (EMGS) celebrates its 50 Anniversary this year, we have come together to review and summarize the seminal advances in the field of environmental epigenomics. Specifically, we focus on the role epigenetics may play in multi and trans-generational transmission of environmentally induced health effects. We also summarize state of the art techniques for evaluating the epigenome, environmental epigenetic analysis, and the emerging field of epigenome editing. Finally, we evaluate transposon epigenetics as they relate to environmental exposures and explore the role of non-coding RNA as biomarkers of environmental exposures. While the field has advanced over the past several decades, including being recognized by EMGS with its own Special Interest Group, recently renamed Epigenomics, we are excited about the opportunities for environmental epigenetic science in the next 50 years. This article is protected by copyright. All rights reserved.]]>
Wed, 31 Dec 1969 19:00:00 EST
Role of epigenetic regulation of Igf2 and H19 in 2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD)-induced ovarian toxicity in offspring rats. Zhang X, Ji M, Tan X, Yu K, Xu L, Chen G, Yu Z
Toxicol Lett (Sep 2019)

2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD) exposure during embryonic gonadal sex determination had been demonstrated to harm the ovarian development. However, its mechanism was unclear and possibly related to epigenetic regulation. In the present study, the pregnant rats were treated with TCDD (100 ng/kg/day or 500 ng/kg/day) or only vehicle and corn oil on the day 8-14 of gestation through the gavage with a stainless-steel feeding needle. The vaginal opening time and estrous cycle of female offspring rats (F1) were monitored twice a day. The ovarian histology, follicle count, real-time PCR, Western Blotting and DNA methylation analysis for Igf2 and H19 were carried out. The results showed that maternal TCDD exposure disrupted estrous cyclicity, resulted in aberrant concentration of serum E2 and FSH, and affected the number of primordial follicles, secondary follicles and corpus luteum. However, TCDD had no effect on the number of primary follicles and atresia follicles. Furthermore, the mRAN expression of imprinted genes Igf2 and H19 was down-regulated, and the IGF2 protein was also down-regulated. TCDD exposure did not alter the mean methylation rate of Igf2 DMR2 and H19 ICR, and only some CpG sites throughout them were hypermethylated in high-dose TCDD rats. In conclusion, maternal exposure of TCDD could affect the ovary development and functions which were possibly associated with down-regulation expression of IGF2 and H19. However, it was not entirely clear whether the impairment of ovary by TCDD was related to the methylation pattern of Igf2 and H19 ICR.]]>
Wed, 31 Dec 1969 19:00:00 EST
Single-Cell Omics Analyses Enabled by Microchip Technologies. Deng Y, Finck A, Fan R
Annu Rev Biomed Eng (Jun 2019)

Single-cell omics studies provide unique information regarding cellular heterogeneity at various levels of the molecular biology central dogma. This knowledge facilitates a deeper understanding of how underlying molecular and architectural changes alter cell behavior, development, and disease processes. The emerging microchip-based tools for single-cell omics analysis are enabling the evaluation of cellular omics with high throughput, improved sensitivity, and reduced cost. We review state-of-the-art microchip platforms for profiling genomics, epigenomics, transcriptomics, proteomics, metabolomics, and multi-omics at single-cell resolution. We also discuss the background of and challenges in the analysis of each molecular layer and integration of multiple levels of omics data, as well as how microchip-based methodologies benefit these fields. Additionally, we examine the advantages and limitations of these approaches. Looking forward, we describe additional challenges and future opportunities that will facilitate the improvement and broad adoption of single-cell omics in life science and medicine.]]>
Wed, 31 Dec 1969 19:00:00 EST
Origins of DNA methylation defects in Wilms tumors. Anvar Z, Acurzio B, Roma J, Cerrato F, Verde G
Cancer Lett (Aug 2019)

Wilms tumor is an embryonic renal cancer that typically presents in early childhood and accounts for 7% of all paediatric cancers. Different genetic alterations have been described in this malignancy, however, only a few of them are associated with a majority of Wilms tumors. Alterations in DNA methylation, in contrast, are frequent molecular defects observed in most cases of Wilms tumors. How these epimutations are established in this tumor is not yet completely clear. The recent identification of the molecular actors required for the epigenetic reprogramming during embryogenesis suggests novel possible mechanisms responsible for the DNA methylation defects in Wilms tumor. Here, we provide an overview of the DNA methylation alterations observed in this malignancy and discuss the distinct molecular mechanisms by which these epimutations can arise.]]>
Wed, 31 Dec 1969 19:00:00 EST
Unbalanced segregation of a paternal t(9;11)(p24.3;p15.4) translocation causing familial Beckwith-Wiedemann syndrome: a case report. Lekszas C, Nanda I, Vona B, Böck J, Ashrafzadeh F, Donyadideh N, Ebrahimzadeh F, Ahangari N, Maroofian R, Karimiani EG, Haaf T
BMC Med Genomics (Jun 2019)

The vast majority of cases with Beckwith-Wiedemann syndrome (BWS) are caused by a molecular defect in the imprinted chromosome region 11p15.5. The underlying mechanisms include epimutations, uniparental disomy, copy number variations, and structural rearrangements. In addition, maternal loss-of-function mutations in CDKN1C are found. Despite growing knowledge on BWS pathogenesis, up to 20% of patients with BWS phenotype remain without molecular diagnosis.]]>
Wed, 31 Dec 1969 19:00:00 EST
Paternal benzo[a]pyrene exposure alters the sperm DNA methylation levels of imprinting genes in F0 generation mice and their unexposed F1-2 male offspring. Zhang W, Yang J, Lv Y, Li S, Qiang M
Chemosphere (Aug 2019)

Benzo[a]pyrene (BaP) is an environmental pollutant known to cause teratogenesis. However, the mechanism underlying this teratogenic effect is not fully understood. Recently, the alteration of DNA methylation of imprinting genes has emerged as a specific epigenetic mechanism linking the impact of environmental pollutants on embryonic development to paternal exposures. The aim of this study was to investigate the transgenerational effects of paternal BaP exposure on the imprinting genes in mouse sperm DNA.]]>
Wed, 31 Dec 1969 19:00:00 EST
Characterization of bovine (Bos taurus) imprinted genes from genomic to amino acid attributes by data mining approaches. Karami K, Zerehdaran S, Javadmanesh A, Shariati MM, Fallahi H
PLoS One (2019)

Genomic imprinting results in monoallelic expression of genes in mammals and flowering plants. Understanding the function of imprinted genes improves our knowledge of the regulatory processes in the genome. In this study, we have employed classification and clustering algorithms with attribute weighting to specify the unique attributes of both imprinted (monoallelic) and biallelic expressed genes. We have obtained characteristics of 22 known monoallelically expressed (imprinted) and 8 biallelic expressed genes that have been experimentally validated alongside 208 randomly selected genes in bovine (Bos taurus). Attribute weighting methods and various supervised and unsupervised algorithms in machine learning were applied. Unique characteristics were discovered and used to distinguish mono and biallelic expressed genes from each other in bovine. To obtain the accuracy of classification, 10-fold cross-validation with concerning each combination of attribute weighting (feature selection) and machine learning algorithms, was used. Our approach was able to accurately predict mono and biallelic genes using the genomics and proteomics attributes.]]>
Wed, 31 Dec 1969 19:00:00 EST
miR-412-5p targets Xpo1 to regulate angiogenesis in hemorrhoid tissue. Wang C, Lu H, Luo C, Song C, Wang Q, Peng Y, Xin Y, Liu T, Yang W
Gene (Jul 2019)

Hemorrhoid is a common and recurrent proctological disease, which is often accompanied by angiogenesis and edema. MicroRNAs in the DLK1-DIO3 imprinted clusters are involved in the development and pathogenesis of mammalian hemorrhoids. Results of the present study indicated multiple, differential expression of DLK1-DIO3 imprinted cluster microRNA between hemorrhoid and normal tissues, where miR-412-5p expression in hemorrhoid tissue was significantly decreased. Fluorescein reporter assays showed that miR-412-5p silenced Xpo1 mRNA expression by targeting its 3'-UTR. Overexpression of miR-412-5p in human umbilical vein endothelial cells (HUVECs) indicated that proliferation, migration and formation of vascular structures in HUVECs were inhibited in vitro. In addition, overexpression of miR-412-5p significantly inhibited Xpo1 expression and promoted upregulation of the p53 protein and its retention in the nucleus. Simultaneously, expression of p66 and p16 proteins was activated. In summary, downregulation of endogenous miR-412-5p expression in hemorrhoid vascular endothelial cells leads to high expression of the target gene Xpo1 and translocation of the p53 protein out of the nucleus, rendering it unable to activate p66 and p16. This ultimately weakens regulation of the vascular endothelial cell cycle, thereby accelerating the division of hemorrhoid vascular endothelial cells, leading to angiogenesis.]]>
Wed, 31 Dec 1969 19:00:00 EST
Next generation sequencing data for use in risk assessment. Merrick BA
Curr Opin Toxicol (Dec 2019)

Next generation sequencing (NGS) represents several powerful platforms that have revolutionized RNA and DNA analysis. The parallel sequencing of millions of DNA molecules can provide mechanistic insights into toxicology and provide new avenues for biomarker discovery with growing relevance for risk assessment. The evolution of NGS technologies has improved over the last decade with increased sensitivity and accuracy to foster new biomarker assays from tissue, blood and other biofluids. NGS sequencing technologies can identify transcriptional changes and genomic targets with base pair precision in response to chemical exposure. Further, there are several exciting movements within the toxicology community that incorporate NGS platforms into new strategies for more rapid toxicological characterizations. These include the Tox21 in vitro high throughput transcriptomic screening program, development of organotypic spheroids, alternative animal models, mining archival tissues, liquid biopsy and epigenomics. This review will describe NGS-based technologies, demonstrate how they can be used as tools for target discovery in tissue and blood, and suggest how they might be applied for risk assessment.]]>
Wed, 31 Dec 1969 19:00:00 EST
Whole genome bisulfite sequencing of Down syndrome brain reveals regional DNA hypermethylation and novel disorder insights. Laufer BI, Hwang H, Vogel Ciernia A, Mordaunt CE, LaSalle JM
Epigenetics (Jul 2019)

Down Syndrome (DS) is the most common genetic cause of intellectual disability, in which an extra copy of human chromosome 21 (HSA21) affects regional DNA methylation profiles across the genome. Although DNA methylation has been previously examined at select regulatory regions across the genome in a variety of DS tissues and cells, differentially methylated regions (DMRs) have yet to be examined in an unbiased sequencing-based approach. Here, we present the first analysis of DMRs from whole genome bisulfite sequencing (WGBS) data of human DS and matched control brain, specifically frontal cortex. While no global differences in DNA methylation were observed, we identified 3,152 DS-DMRs across the entire genome, the majority of which were hypermethylated in DS. DS-DMRs were significantly enriched at CpG islands and de-enriched at specific gene body and regulatory regions. Functionally, the hypermethylated DS-DMRs were enriched for one-carbon metabolism, membrane transport, and glutamatergic synaptic signalling, while the hypomethylated DMRs were enriched for proline isomerization, glial immune response, and apoptosis. Furthermore, in a cross-tissue comparison to previous studies of DNA methylation from diverse DS tissues and reference epigenomes, hypermethylated DS-DMRs showed a strong cross-tissue concordance, while a more tissue-specific pattern was observed for the hypomethylated DS-DMRs. Overall, this approach highlights that low-coverage WGBS of clinical samples can identify epigenetic alterations to known biological pathways, which are potentially relevant to therapeutic treatments and include metabolic pathways. These results also provide new insights into the genome-wide effects of genetic alterations on DNA methylation profiles indicative of altered neurodevelopment and brain function.]]>
Wed, 31 Dec 1969 19:00:00 EST
FEZF1-AS1: A novel vital oncogenic lncRNA in multiple human malignancies. Shi C, Sun L, Song Y
Biosci Rep (Jun 2019)

Long noncoding RNAs(LncRNAs) refer to the RNA with a length of > 200 nucleotides, which lack or have no open reading coding frame and have higher tissue and organ specificity compared with the protein coding genes. A surging number of studies have shown that lncRNA is involved in numerous essential regulatory processes, such as X chromosome silencing, genomic imprinting, chromatin modification, transcriptional activation, transcriptional interference and nuclear transport, which are closely related to the occurrence and development of human malignancies. FEZ family Zinc Finger 1-Antisense RNA 1 (FEZF1-AS1) of FEZ family is a recently discovered lncRNA. FEZF1-AS1 is highly expressed in pancreatic cancer, colorectal cancer, lung adenocarcinoma and other human malignancies,and is associated with poor prognosis.As an oncogene, it plays crucial role in the proliferation, migration, invasion and warburg effect of various tumor cells.In addition, FEZF1-AS1 is also involved in the regulation of multiple signal pathways such as Epithelial-Mesenchymal Transition (EMT), Signal Transducer And Activator Of Transcription 3(STAT3), and Wnt/ β-catenin. In this paper, the recent research progress of FEZF1-AS1 in tumorigenesis and development is reviewed systematically.]]>
Wed, 31 Dec 1969 19:00:00 EST
Invited review: Advances and challenges in application of feedomics to improve dairy cow production and health. Sun HZ, Plastow G, Guan LL
J Dairy Sci (Jul 2019)

Dairy cattle science has evolved greatly over the past century, contributing significantly to the improvement in milk production achieved today. However, a new approach is needed to meet the increasing demand for milk production and address the increased concerns about animal health and welfare. It is now easy to collect and access large and complex data sets consisting of molecular, physiological, and metabolic data as well as animal-level data (such as behavior). This provides new opportunities to better understand the mechanisms regulating cow performance. The recently proposed concept of feedomics could help achieve this goal by increasing our understanding of interactions between the different components or levels and their impact on animal production. Feedomics is an emerging field that integrates a range of omics technologies (e.g., genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, and metatranscriptomics) to provide these insights. In this way, we can identify the best strategies to improve overall animal productivity, product quality, welfare, and health. This approach can help research communities elucidate the complex interactions among nutrition, environment, management, animal genetics, metabolism, physiology, and the symbiotic microbiota. In this review, we summarize the outcomes of the most recent research on omics in dairy cows and highlight how an integrated feedomics approach could be applied in the future to improve dairy cow production and health. Specifically, we focus on 2 topics: (1) improving milk yield and milk quality, and (2) understanding metabolic physiology in transition dairy cows, which are 2 important challenges faced by the dairy industry worldwide.]]>
Wed, 31 Dec 1969 19:00:00 EST
Leducq Epigenetics of Atherosclerosis Network. de Winther MPJ, Glass CK
Circ Res (Jun 2019)

Wed, 31 Dec 1969 19:00:00 EST
Possibility of early diagnosis in a fetus affected by Prader‑Willi syndrome with maternal hetero‑UPD15: A lesson to be learned. Dong Y, Liu S, Li J, Li J, Chen Q, Luo J, Li C, Li H, Qi H, Li R
Mol Med Rep (Jul 2019)

Prader‑Willi syndrome (PWS), a complicated neurodevelopmental disorder arising from errors in genomic imprinting, is characterized by evident hypotonia along with feeding difficulties and the absence of crying in early infancy. Hyperphagia and obesity are not uncommon in patients with PWS, usually accompanied by intellectual disability, cognitive impairment, short stature, small hands and feet, as well as hypogonadism and typical facial features. Due to the severe complications associated with PWS, a thorough understanding of its features and an early diagnosis, preferably in the fetal period, are important for clinical management. According to previous studies, prenatal diagnosis has been confirmed in only a few cases of PWS, using ultrasound, or as an accidental finding by cytogenetic molecular techniques, as no precise fetal phenotype has been defined. In this present study, an infant with PWS arising from maternal heterodisomy of chromosome 15 is described. This is a typical case of missed diagnosis by fetal ultrasound examination, chromosome karyotype analysis and chromosome microarray (CMA) conducted during the pregnancy. To delineate the complex prenatal characteristics of a fetus with PWS, prenatally‑diagnosed cases of PWS described in the literature were reviewed. This present study indicated that although prenatal signs are not sufficient for a diagnosis to be confirmed, a comprehensive consideration of these signs is important in leading to a diagnosis of suspected PWS, and thus prompts further prenatal investigations using molecular genetic tools. Furthermore, this present study also suggested that CMA can lead to a missed diagnosis of PWS/Angelman syndrome and other imprinting disorders despite its high value in the detection of copy‑number variants in individuals with developmental delay. If clinical signs strongly suggest PWS, other prenatal molecular genetic investigations, including methylation tests and short tandem repeat‑based linkage analysis for uniparental disomy, are recommended as an additional tool to aid diagnosis.]]>
Wed, 31 Dec 1969 19:00:00 EST
Effect of smoking on the DNA methylation pattern of the SOCS1 promoter in epithelial cells from the saliva of patients with chronic periodontitis. de J H Martinez C, Villafuerte KRV, Luchiari HR, de O Cruz J, Sales M, Palioto DB, Messora MR, Souza SLS, Taba M, Ramos ES, Novaes AB
J Periodontol (Jun 2019)

The aim of the present study was to evaluate the methylation pattern in the suppressor of cytokine signaling 1 (SOCS1) gene in smokers and non-smokers with chronic periodontitis.]]>
Wed, 31 Dec 1969 19:00:00 EST
TET enzymes, DNA demethylation and pluripotency. Ross SE, Bogdanovic O
Biochem Soc Trans (Jun 2019)

Ten-eleven translocation (TET) methylcytosine dioxygenases (TET1, TET2, TET3) actively cause demethylation of 5-methylcytosine (5mC) and produce and safeguard hypomethylation at key regulatory regions across the genome. This 5mC erasure is particularly important in pluripotent embryonic stem cells (ESCs) as they need to maintain self-renewal capabilities while retaining the potential to generate different cell types with diverse 5mC patterns. In this review, we discuss the multiple roles of TET proteins in mouse ESCs, and other vertebrate model systems, with a particular focus on TET functions in pluripotency, differentiation, and developmental DNA methylome reprogramming. Furthermore, we elaborate on the recently described non-catalytic roles of TET proteins in diverse biological contexts. Overall, TET proteins are multifunctional regulators that through both their catalytic and non-catalytic roles carry out myriad functions linked to early developmental processes.]]>
Wed, 31 Dec 1969 19:00:00 EST
WashU Epigenome Browser update 2019. Li D, Hsu S, Purushotham D, Sears RL, Wang T
Nucleic Acids Res (Jun 2019)

The WashU Epigenome Browser (https://epigenomegateway.wustl.edu/) provides visualization, integration and analysis tools for epigenomic datasets. Since 2010, it has provided the scientific community with data from large consortia including the Roadmap Epigenomics and the ENCODE projects. Recently, we refactored the codebase, redesigned the user interface, and developed various novel features. New features include: (i) visualization using virtual reality (VR), which has implications in biology education and the study of 3D chromatin structure; (ii) expanded public data hubs, including data from the 4DN, ENCODE, Roadmap Epigenomics, TaRGET, IHEC and TCGA consortia; (iii) a more responsive user interface; (iv) a history of interactions, which enables undo and redo; (v) a feature we call Live Browsing, which allows multiple users to collaborate remotely on the same session; (vi) the ability to visualize local tracks and data hubs. Amazon Web Services also hosts the redesign at https://epigenomegateway.org/.]]>
Wed, 31 Dec 1969 19:00:00 EST
Predicting three-dimensional genome organization with chromatin states. Qi Y, Zhang B
PLoS Comput Biol (Jun 2019)

We introduce a computational model to simulate chromatin structure and dynamics. Starting from one-dimensional genomics and epigenomics data that are available for hundreds of cell types, this model enables de novo prediction of chromatin structures at five-kilo-base resolution. Simulated chromatin structures recapitulate known features of genome organization, including the formation of chromatin loops, topologically associating domains (TADs) and compartments, and are in quantitative agreement with chromosome conformation capture experiments and super-resolution microscopy measurements. Detailed characterization of the predicted structural ensemble reveals the dynamical flexibility of chromatin loops and the presence of cross-talk among neighboring TADs. Analysis of the model's energy function uncovers distinct mechanisms for chromatin folding at various length scales and suggests a need to go beyond simple A/B compartment types to predict specific contacts between regulatory elements using polymer simulations.]]>
Wed, 31 Dec 1969 19:00:00 EST
XL-DNase-seq: improved footprinting of dynamic transcription factors. Oh KS, Ha J, Baek S, Sung MH
Epigenetics Chromatin (Jun 2019)

As the cost of high-throughput sequencing technologies decreases, genome-wide chromatin accessibility profiling methods such as the assay of transposase-accessible chromatin using sequencing (ATAC-seq) are employed widely, with data accumulating at an unprecedented rate. However, accurate inference of protein occupancy requires higher-resolution footprinting analysis where major hurdles exist, including the sequence bias of nucleases and the short-lived chromatin binding of many transcription factors (TFs) with consequent lack of footprints.]]>
Wed, 31 Dec 1969 19:00:00 EST