'; ?> 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 Tue, 19 Mar 2019 08:14:47 EDT Tue, 19 Mar 2019 08:14:47 EDT jirtle@radonc.duke.edu james001@jirtle.com Processing of big heterogeneous genomic datasets for tertiary analysis of Next Generation Sequencing data. Masseroli M, Canakoglu A, Pinoli P, Kaitoua A, Gulino A, Horlova O, Nanni L, Bernasconi A, Perna S, Stamoulakatou E, Ceri S
Bioinformatics (Mar 2019)

We previously proposed a paradigm shift in genomic data management, based on the Genomic Data Model (GDM) for mediating existing data formats and on the GenoMetric Query Language (GMQL) for supporting, at a high level of abstraction, data extraction and the most common data-driven computations required by tertiary data analysis of Next Generation Sequencing datasets. Here, we present a new GMQL-based system with enhanced accessibility, portability, scalability and performance.]]>
Wed, 31 Dec 1969 19:00:00 EST
Biomarkers: What Role Do They Play (If Any) for Diagnosis, Prognosis and Tumor Response Prediction for Hepatocellular Carcinoma? Harding JJ, Khalil DN, Abou-Alfa GK
Dig Dis Sci (Mar 2019)

Hepatocellular carcinoma (HCC) is a common illness that affects patients worldwide. The disease remains poorly understood though several recent advances have increased the understanding of HCC biology and treatment.]]>
Wed, 31 Dec 1969 19:00:00 EST
Genomic imprinting disorders: lessons on how genome, epigenome and environment interact. Monk D, Mackay DJG, Eggermann T, Maher ER, Riccio A
Nat Rev Genet (Apr 2019)

Genomic imprinting, the monoallelic and parent-of-origin-dependent expression of a subset of genes, is required for normal development, and its disruption leads to human disease. Imprinting defects can involve isolated or multilocus epigenetic changes that may have no evident genetic cause, or imprinting disruption can be traced back to alterations of cis-acting elements or trans-acting factors that control the establishment, maintenance and erasure of germline epigenetic imprints. Recent insights into the dynamics of the epigenome, including the effect of environmental factors, suggest that the developmental outcomes and heritability of imprinting disorders are influenced by interactions between the genome, the epigenome and the environment in germ cells and early embryos.]]>
Wed, 31 Dec 1969 19:00:00 EST
AtMBD4: A methylated DNA binding protein negatively regulates a subset of phosphate starvation genes. Parida AP, Sharma A, Sharma AK
J Biosci (Mar 2019)

DNA methylation is an important epigenetic modification that governs transcriptional regulation. The methylation mark is read by a special class of proteins called methyl-CpG-binding domain proteins. The role of DNA methylation has been found in X-chromosome inactivation, genomic imprinting, transposon silencing, and self-incompatibility. Recently, remodeling of global DNA methylation was demonstrated in Arabidopsis during low phosphate availability. The present study reports that gene of negatively regulates phosphate starvation. The T-DNA insertion mutation at the locus exhibited altered root architecture as compared to wild-type plants. Using microarray hybridization and analysis, an increased transcript accumulation of 242 genes was observed in the mutant. Many of these genes were related to phosphate transporters and transcription factors, involved in phosphate starvation response. Comparison of data of atmbd4 mutant with publicly available microarray data of phosphate starvation response indicated the role of AtMBD4 protein in phosphate starvation response. Further, promoter analysis of up-regulated genes suggested that cis-regulatory elements like MBS, W-box, and B1BS are more prominent in the promoters of up-regulated genes. Upon performing a methylation-specific PCR, a decreased DNA methylation in the promoter regions of up-regulated genes was observed. The accumulation of anthocyanin and inorganic phosphate in the atmbd4 mutant was found to be higher than the wild-type plant. Altered root morphology, up-regulation of phosphate starvation-induced genes in atmbd4 mutant suggests that AtMBD4 negatively regulates the phosphate starvation response.]]>
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 (Mar 2019)

The study of single-cell omics provides unique information regarding the heterogeneity of cellular populations at various levels of the central dogma of molecular biology. 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. Expected final online publication date for the Annual Review of Biomedical Engineering Volume 21 is June 4, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.]]>
Wed, 31 Dec 1969 19:00:00 EST
The effects of Assisted Reproductive Technologies on genomic imprinting in the placenta. Rhon-Calderon EA, Vrooman LA, Riesche L, Bartolomei MS
Placenta (Mar 2019)

The placenta is a complex and poorly understood organ, which serves as the connection between the mother and the developing fetus. Genomic imprinting, defined as a regulatory process resulting in the expression of a gene in a parent-of-origin-specific manner, plays an important role in fetal development and placental function. Disturbances that occur during the establishment and maintenance of imprinting could compromise the placenta and fetus, and ultimately, offspring health. Assisted Reproductive Technologies (ART) have been widely used to overcome infertility, however experimental studies have shown that ART procedures affect placentation and the expression of imprinted genes. Here we briefly review the role of imprinted genes in placental development and the evidence from mouse and human studies suggesting ART disrupts imprinted gene regulation in the placenta.]]>
Wed, 31 Dec 1969 19:00:00 EST
Shift work, DNA methylation and epigenetic age. White AJ, Kresovich JK, Xu Z, Sandler DP, Taylor JA
Int J Epidemiol (Mar 2019)

Shift work has been associated with increased risk of age-related morbidity and mortality. Biological age, estimated using DNA methylation (DNAm), may quantify the biological consequences of shift work on the risk of age-related disease. We examined whether prior employment in shift-working occupations was associated with epigenetic age acceleration.]]>
Wed, 31 Dec 1969 19:00:00 EST
New frontiers in precision medicine for sepsis-induced immunoparalysis. Bruse N, Leijte GP, Pickkers P, Kox M
Expert Rev Clin Immunol (Mar 2019)

In the last decade, the sepsis research field has shifted focus from targeting hyperinflammation to reversing sepsis-induced immunoparalysis. Sepsis-induced immunoparalysis is very heterogeneous: the magnitude and the nature of the underlying immune defects differ considerably between patients, but also within individuals over time. Therefore, a 'one-treatment-fits-all' strategy for sepsis-induced immunoparalysis is bound to fail, and an individualized 'precision medicine' approach is required. Such a strategy is nevertheless hampered by the unsuitability of the currently available markers to identify the many immune defects that can manifest in individual patients. Areas covered: We describe the currently available markers for sepsis-induced immunoparalysis and limitations pertaining to their use. Furthermore, future prospects and caveats are discussed, focusing on 'omics' approaches: genomics, transcriptomics, epigenomics, and metabolomics. Finally, we present a contemporary overview of adjuvant immunostimulatory therapies. Expert opinion: The integration of multiple omics techniques offers a systems biology approach which can yield biomarker profiles that accurately and comprehensively gauge the extent and nature of sepsis-induced immunoparalysis. We expect this development to be instrumental in facilitating precision medicine for sepsis-induced immunoparalysis, consisting of the application of targeted immunostimulatory therapies and follow-up measurements to monitor the response to treatment and to titrate or adjust medication.]]>
Wed, 31 Dec 1969 19:00:00 EST
DMSO induces drastic changes in human cellular processes and epigenetic landscape in vitro. Verheijen M, Lienhard M, Schrooders Y, Clayton O, Nudischer R, Boerno S, Timmermann B, Selevsek N, Schlapbach R, Gmuender H, Gotta S, Geraedts J, Herwig R, Kleinjans J, Caiment F
Sci Rep (Mar 2019)

Though clinical trials for medical applications of dimethyl sulfoxide (DMSO) reported toxicity in the 1960s, later, the FDA classified DMSO in the safest solvent category. DMSO became widely used in many biomedical fields and biological effects were overlooked. Meanwhile, biomedical science has evolved towards sensitive high-throughput techniques and new research areas, including epigenomics and microRNAs. Considering its wide use, especially for cryopreservation and in vitro assays, we evaluated biological effect of DMSO using these technological innovations. We exposed 3D cardiac and hepatic microtissues to medium with or without 0.1% DMSO and analyzed the transcriptome, proteome and DNA methylation profiles. In both tissue types, transcriptome analysis detected >2000 differentially expressed genes affecting similar biological processes, thereby indicating consistent cross-organ actions of DMSO. Furthermore, microRNA analysis revealed large-scale deregulations of cardiac microRNAs and smaller, though still massive, effects in hepatic microtissues. Genome-wide methylation patterns also revealed tissue-specificity. While hepatic microtissues demonstrated non-significant changes, findings from cardiac microtissues suggested disruption of DNA methylation mechanisms leading to genome-wide changes. The extreme changes in microRNAs and alterations in the epigenetic landscape indicate that DMSO is not inert. Its use should be reconsidered, especially for cryopreservation of embryos and oocytes, since it may impact embryonic development.]]>
Wed, 31 Dec 1969 19:00:00 EST
Integration of microbiology, molecular pathology, and epidemiology: a new paradigm to explore the pathogenesis of microbiome-driven neoplasms. Hamada T, Nowak JA, Milner DA, Song M, Ogino S
J Pathol (Apr 2019)

Molecular pathological epidemiology (MPE) is an integrative transdisciplinary field that addresses heterogeneous effects of exogenous and endogenous factors (collectively termed 'exposures'), including microorganisms, on disease occurrence and consequences, utilising molecular pathological signatures of the disease. In parallel with the paradigm of precision medicine, findings from MPE research can provide aetiological insights into tailored strategies of disease prevention and treatment. Due to the availability of molecular pathological tests on tumours, the MPE approach has been utilised predominantly in research on cancers including breast, lung, prostate, and colorectal carcinomas. Mounting evidence indicates that the microbiome (inclusive of viruses, bacteria, fungi, and parasites) plays an important role in a variety of human diseases including neoplasms. An alteration of the microbiome may be not only a cause of neoplasia but also an informative biomarker that indicates or mediates the association of an epidemiological exposure with health conditions and outcomes. To adequately educate and train investigators in this emerging area, we herein propose the integration of microbiology into the MPE model (termed 'microbiology-MPE'), which could improve our understanding of the complex interactions of environment, tumour cells, the immune system, and microbes in the tumour microenvironment during the carcinogenic process. Using this approach, we can examine how lifestyle factors, dietary patterns, medications, environmental exposures, and germline genetics influence cancer development and progression through impacting the microbial communities in the human body. Further integration of other disciplines (e.g. pharmacology, immunology, nutrition) into microbiology-MPE would expand this developing research frontier. With the advent of high-throughput next-generation sequencing technologies, researchers now have increasing access to large-scale metagenomics as well as other omics data (e.g. genomics, epigenomics, proteomics, and metabolomics) in population-based research. The integrative field of microbiology-MPE will open new opportunities for personalised medicine and public health. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenomics in an extraterrestrial environment: organ-specific alteration of DNA methylation and gene expression elicited by spaceflight in Arabidopsis thaliana. Zhou M, Sng NJ, LeFrois CE, Paul AL, Ferl RJ
BMC Genomics (Mar 2019)

Plants adapted to diverse environments on Earth throughout their evolutionary history, and developed mechanisms to thrive in a variety of terrestrial habitats. When plants are grown in the novel environment of spaceflight aboard the International Space Station (ISS), an environment completely outside their evolutionary history, they respond with unique alterations to their gene expression profile. Identifying the genes important for physiological adaptation to spaceflight and dissecting the biological processes and pathways engaged by plants during spaceflight has helped reveal spaceflight adaptation, and has furthered understanding of terrestrial growth processes. However, the underlying regulatory mechanisms responsible for these changes in gene expression patterns are just beginning to be explored. Epigenetic modifications, such as DNA methylation at position five in cytosine, has been shown to play a role in the physiological adaptation to adverse terrestrial environments, and may play a role in spaceflight as well.]]>
Wed, 31 Dec 1969 19:00:00 EST
Ectopic expression of DNA methyltransferases DNMT3A2 and DNMT3L leads to aberrant hypermethylation and postnatal lethality in mice. Sasaki K, Hara S, Yamakami R, Sato Y, Hasegawa S, Kono T, Morohaku K, Obata Y
Mol Reprod Dev (Mar 2019)

DNA methylation is generally known to inactivate gene expression. The DNA methyltransferases (DNMTs), DNMT3A and DNMT3B, catalyze somatic cell lineage-specific DNA methylation, while DNMT3A and DNMT3L catalyze germ cell lineage-specific DNA methylation. How such lineage- and gene-specific DNA methylation patterns are created remains to be elucidated. To better understand the regulatory mechanisms underlying DNA methylation, we generated transgenic mice that constitutively expressed DNMT3A and DNMT3L, and analyzed DNA methylation, gene expression, and their subsequent impact on ontogeny. All transgenic mice were born normally but died within 20 weeks accompanied with cardiac hypertrophy. Several genes were repressed in the hearts of transgenic mice compared with those in wild-type mice. CpG islands of these downregulated genes were highly methylated in the transgenic mice. This abnormal methylation occurred in the perinatal stage. Conversely, monoallelic DNA methylation at imprinted loci was faithfully maintained in all transgenic mice, except H19. Thus, the loci preferred by DNMT3A and DNMT3L differ between somatic and germ cell lineages.]]>
Wed, 31 Dec 1969 19:00:00 EST
The hyper-activation of transcriptional enhancers in breast cancer. Li QL, Wang DY, Ju LG, Yao J, Gao C, Lei PJ, Li LY, Zhao XL, Wu M
Clin Epigenetics (Mar 2019)

Activation of transcription enhancers, especially super-enhancers, is one of the critical epigenetic features of tumorigenesis. However, very few studies have systematically identified the enhancers specific in cancer tissues.]]>
Wed, 31 Dec 1969 19:00:00 EST
Paediatrician's guide to epigenetics. Byrne L, Drake AJ
Arch Dis Child (Mar 2019)

Epigenetic regulation of gene expression is critical for normal development. Dysregulation of the epigenome can lead to the development and progression of a number of diseases relevant to paediatricians, including disorders of genomic imprinting and malignancies. It has long been recognised that early life events have implications for future disease risk, and epigenetic modifications may play a role in this, although further high-quality research is needed to better understand the underlying mechanisms. Research in the field of epigenetics will contribute to a greater understanding of growth, development and disease; however, paediatricians need to be able to interpret such research critically, in order to use the potential advances brought about through epigenetic studies while appreciating their limitations.]]>
Wed, 31 Dec 1969 19:00:00 EST
The immune milieu of cholangiocarcinoma: From molecular pathogenesis to precision medicine. Rimassa L, Personeni N, Aghemo A, Lleo A
J Autoimmun (Mar 2019)

Cholangiocarcinoma (CCA) is a deadly cancer of the biliary epithelium with limited therapeutic options. It is a heterogeneous group of cancer that could develop at any level from the biliary tree and is currently classified into intrahepatic, perihilar and distal based on its anatomical location. With incidence and mortality rates currently increasing, it is now the second most common type of primary liver cancer and represents up to 3% of all gastrointestinal malignancies. High-throughput genomics and epigenomics have greatly increased our understanding of CCA underlying biology, however its pathogenesis remains largely unknown. CCA is characterized by a highly desmoplastic microenvironment containing stromal cells, mainly cancer-associated fibroblasts, infiltrating tumor epithelium. Tumor microenvironment in CCA is a highly dynamic environment that, besides stromal and endothelial cells, encompass also an abundance of immune cells, of both the innate and adaptive immune system (including tumor-associated macrophages, neutrophils, natural killer cells, and T and B lymphocytes) and abundant proliferative factors. It is orchestrated by multiple soluble factors and signals, that eventually define a tumor growth-permissive microenvironment. Through complicate interactions with CCA cells, tumor microenvironment profoundly affects the proliferative and invasive abilities of epithelial cancer cells and plays an important role in accelerating neovascularization and preventing apoptosis of neoplastic cells. In this review, we discuss recent developments regarding the characteristics of the tumor microenvironment, the role of each cellular population, and their multiarticulate interaction with the malignant population. Further we discuss innovative treatment approaches, including immunotherapy, and how identification of CCA secreted factors by both the stromal component and immune cell subsets are leading towards a precision medicine in CCA.]]>
Wed, 31 Dec 1969 19:00:00 EST
Targeted DNA Methylation Profiling of Human Cardiac Tissue Reveals Novel Epigenetic Traits and Gene Deregulation Across Different Heart Failure Patient Subtypes. Glezeva N, Moran B, Collier P, Moravec CS, Phelan D, Donnellan E, Russell-Hallinan A, O'Connor DP, Gallagher WM, Gallagher J, McDonald K, Ledwidge M, Baugh J, Das S, Watson CJ
Circ Heart Fail (Mar 2019)

Limited knowledge exists of the extent of epigenetic alterations, such as DNA methylation, in heart failure (HF). We conducted targeted DNA methylation sequencing to identify DNA methylation alterations in coding and noncoding RNA (ncRNA) across different etiological subtypes of HF.]]>
Wed, 31 Dec 1969 19:00:00 EST
Link between depression and cardiovascular diseases due to epigenomics and proteomics: Focus on energy metabolism. Kahl KG, Stapel B, Frieling H
Prog Neuropsychopharmacol Biol Psychiatry (03 2019)

Major depression is the most common mental disorder and a leading cause of years lived with disability. In addition to the burden attributed to depressive symptoms and reduced daily life functioning, people with major depression are at increased risk of premature mortality, particularly due to cardiovascular diseases. Several studies point to a bi-directional relation between major depression and cardiovascular diseases, thereby indicating that both diseases may share common pathophysiological pathways. These include lifestyle factors (e.g. physical activity, smoking behavior), dysfunctions of endocrine systems (e.g. hypothalamus-pituitary adrenal axis), and a dysbalance of pro- and anti-inflammatory factors. Furthermore, recent research point to the role of epigenomic and proteomic factors, that are reviewed here with a particular focus on the mitochondrial energy metabolism.]]>
Wed, 31 Dec 1969 19:00:00 EST
Comprehensive, integrated, and phased whole-genome analysis of the primary ENCODE cell line K562. Zhou B, Ho SS, Greer SU, Zhu X, Bell JM, Arthur JG, Spies N, Zhang X, Byeon S, Pattni R, Ben-Efraim N, Haney MS, Haraksingh RR, Song G, Ji HP, Perrin D, Wong WH, Abyzov A, Urban AE
Genome Res (03 2019)

K562 is widely used in biomedical research. It is one of three tier-one cell lines of ENCODE and also most commonly used for large-scale CRISPR/Cas9 screens. Although its functional genomic and epigenomic characteristics have been extensively studied, its genome sequence and genomic structural features have never been comprehensively analyzed. Such information is essential for the correct interpretation and understanding of the vast troves of existing functional genomics and epigenomics data for K562. We performed and integrated deep-coverage whole-genome (short-insert), mate-pair, and linked-read sequencing as well as karyotyping and array CGH analysis to identify a wide spectrum of genome characteristics in K562: copy numbers (CN) of aneuploid chromosome segments at high-resolution, SNVs and indels (both corrected for CN in aneuploid regions), loss of heterozygosity, megabase-scale phased haplotypes often spanning entire chromosome arms, structural variants (SVs), including small and large-scale complex SVs and nonreference retrotransposon insertions. Many SVs were phased, assembled, and experimentally validated. We identified multiple allele-specific deletions and duplications within the tumor suppressor gene Taking aneuploidy into account, we reanalyzed K562 RNA-seq and whole-genome bisulfite sequencing data for allele-specific expression and allele-specific DNA methylation. We also show examples of how deeper insights into regulatory complexity are gained by integrating genomic variant information and structural context with functional genomics and epigenomics data. Furthermore, using K562 haplotype information, we produced an allele-specific CRISPR targeting map. This comprehensive whole-genome analysis serves as a resource for future studies that utilize K562 as well as a framework for the analysis of other cancer genomes.]]>
Wed, 31 Dec 1969 19:00:00 EST
Machine Learning Polymer Models of Three-Dimensional Chromatin Organization in Human Lymphoblastoid Cells. Al Bkhetan Z, Kadlof M, Kraft A, Plewczynski D
Methods (Mar 2019)

We present machine learning models of human genome three-dimensional structure that combine one dimensional (linear) sequence specificity, epigenomic information and transcription factor binding profiles, with the polymer-based biophysical simulations in order to explain the extensive long-range chromatin looping observed in ChIA-PET experiments for lymphoblastoid cells. Random Forest, Gradient Boosting Machine (GBM), and Deep Learning models were constructed and evaluated, when predicting high resolution interactions within Topologically Associating Domains (TADs). The predicted interactions are consistent with the experimental long-read ChIA-PET interactions mediated by CTCF and RNAPOL2 for GM12878 cell line. The contribution of sequence information and chromatin state defined by epigenomic features to the prediction task is analyzed and reported, when using them separately and combined. Furthermore, we design three-dimensional models of chromatin contact domains (CCDs) using real (ChIA-PET) and predicted looping interactions. Initial results show a similarity between both types of 3D computational models (constructed from experimental or predicted interactions). This observation confirms the association between genome sequence, epigenomic and transcription factor profiles, and three-dimensional interactions.]]>
Wed, 31 Dec 1969 19:00:00 EST
Molecular genetic classification in Prader-Willi syndrome: a multisite cohort study. Butler MG, Hartin SN, Hossain WA, Manzardo AM, Kimonis V, Dykens E, Gold JA, Kim SJ, Weisensel N, Tamura R, Miller JL, Driscoll DJ
J Med Genet (Mar 2019)

Prader-Willi syndrome (PWS) is due to errors in genomic imprinting. PWS is recognised as the most common known genetic cause of life-threatening obesity. This report summarises the frequency and further characterises the PWS molecular classes and maternal age effects.]]>
Wed, 31 Dec 1969 19:00:00 EST