'; ?> 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, 13 Oct 2015 10:15:54 PDT Tue, 13 Oct 2015 10:15:54 PDT jirtle@radonc.duke.edu james001@jirtle.com The use of -omic tools in the study of disease processes in marine bivalve mollusks. Gómez-Chiarri M, Guo X, Tanguy A, He Y, Proestou D
J Invertebr Pathol (Oct 2015)

Our understanding of disease processes and host-pathogen interactions in model species has benefited greatly from the application of medium and high-throughput genomic, metagenomic, epigenomic, transcriptomic, and proteomic analyses. The rate at which new, low-cost, high-throughput -omic technologies are being developed has also led to an expansion in the number of studies aimed at gaining a better understanding of disease processes in bivalves. This review provides a catalogue of the genetic and -omic tools available for bivalve species and examples of how -omics has contributed to the advancement of marine bivalve disease research, with a special focus in the areas of immunity, bivalve-pathogen interactions, mechanisms of disease resistance and pathogen virulence, and disease diagnosis. The analysis of bivalve genomes and transcriptomes has revealed that many immune and stress-related gene families are expanded in the bivalve taxa examined thus far. In addition, the analysis of proteomes confirms that responses to infection are influenced by epigenetic, post-transcriptional, and post-translational modifications. The few studies performed in bivalves show that epigenetic modifications are non-random, suggesting a role for epigenetics in regulating the interactions between bivalves and their environments. Despite the progress -omic tools have enabled in the field of marine bivalve disease processes, there is much more work to be done. To date, only three bivalve genomes have been sequenced completely, with assembly status at different levels of completion. Transcriptome datasets are relatively easy and inexpensive to generate, but their interpretation will benefit greatly from high quality genome assemblies and improved data analysis pipelines. Finally, metagenomic, epigenomic, proteomic, and metabolomic studies focused on bivalve disease processes are currently limited but their expansion should be facilitated as more transcriptome datasets and complete genome sequences become available for marine bivalve species.]]>
Sat, 10 Oct 2015 00:00:00 PDT
CRCDA-Comprehensive resources for cancer NGS data analysis. Thangam M, Gopal RK
Database (Oxford) (2015)

Next generation sequencing (NGS) innovations put a compelling landmark in life science and changed the direction of research in clinical oncology with its productivity to diagnose and treat cancer. The aim of our portal comprehensive resources for cancer NGS data analysis (CRCDA) is to provide a collection of different NGS tools and pipelines under diverse classes with cancer pathways and databases and furthermore, literature information from PubMed. The literature data was constrained to 18 most common cancer types such as breast cancer, colon cancer and other cancers that exhibit in worldwide population. NGS-cancer tools for the convenience have been categorized into cancer genomics, cancer transcriptomics, cancer epigenomics, quality control and visualization. Pipelines for variant detection, quality control and data analysis were listed to provide out-of-the box solution for NGS data analysis, which may help researchers to overcome challenges in selecting and configuring individual tools for analysing exome, whole genome and transcriptome data. An extensive search page was developed that can be queried by using (i) type of data [literature, gene data and sequence read archive (SRA) data] and (ii) type of cancer (selected based on global incidence and accessibility of data). For each category of analysis, variety of tools are available and the biggest challenge is in searching and using the right tool for the right application. The objective of the work is collecting tools in each category available at various places and arranging the tools and other data in a simple and user-friendly manner for biologists and oncologists to find information easier. To the best of our knowledge, we have collected and presented a comprehensive package of most of the resources available in cancer for NGS data analysis. Given these factors, we believe that this website will be an useful resource to the NGS research community working on cancer.Database URL: http://bioinfo.au-kbc.org.in/ngs/ngshome.html.]]>
Fri, 09 Oct 2015 00:00:00 PDT
Overview of 'Omics Technologies for Military Occupational Health Surveillance and Medicine. Bradburne C, Graham D, Kingston HM, Brenner R, Pamuku M, Carruth L
Mil Med (Oct 2015)

Systems biology ('omics) technologies are emerging as tools for the comprehensive analysis and monitoring of human health. In order for these tools to be used in military medicine, clinical sampling and biobanking will need to be optimized to be compatible with downstream processing and analysis for each class of molecule measured. This article provides an overview of 'omics technologies, including instrumentation, tools, and methods, and their potential application for warfighter exposure monitoring. We discuss the current state and the potential utility of personalized data from a variety of 'omics sources including genomics, epigenomics, transcriptomics, metabolomics, proteomics, lipidomics, and efforts to combine their use. Issues in the "sample-to-answer" workflow, including collection and biobanking are discussed, as well as national efforts for standardization and clinical interpretation. Establishment of these emerging capabilities, along with accurate xenobiotic monitoring, for the Department of Defense could provide new and effective tools for environmental health monitoring at all duty stations, including deployed locations.]]>
Thu, 08 Oct 2015 00:00:00 PDT
Deletion of the Snord116/SNORD116 Alters Sleep in Mice and Patients with Prader-Willi Syndrome. Lassi G, Priano L, Maggi S, Garcia-Garcia C, Balzani E, El-Assawy N, Pagani M, Tinarelli F, Giardino D, Mauro A, Peters J, Gozzi A, Grugni G, Tucci V
Sleep (Oct 2015)

Sleep-wake disturbances are often reported in Prader-Willi syndrome (PWS), a rare neurodevelopmental syndrome that is associated with paternally-expressed genomic imprinting defects within the human chromosome region 15q11-13. One of the candidate genes, prevalently expressed in the brain, is the small nucleolar ribonucleic acid-116 (SNORD116). Here we conducted a translational study into the sleep abnormalities of PWS, testing the hypothesis that SNORD116 is responsible for sleep defects that characterize the syndrome.]]>
Thu, 08 Oct 2015 00:00:00 PDT
Microglial Malfunction: The Third Rail in the Development of Alzheimer's Disease. Mhatre SD, Tsai CA, Rubin AJ, James ML, Andreasson KI
Trends Neurosci (Oct 2015)

Studies of Alzheimer's disease (AD) have predominantly focused on two major pathologies: amyloid-β (Aβ) and hyperphosphorylated tau. These misfolded proteins can accumulate asymptomatically in distinct regions over decades. However, significant Aβ accumulation can be seen in individuals who do not develop dementia, and tau pathology limited to the transentorhinal cortex, which can appear early in adulthood, is usually clinically silent. Thus, an interaction between these pathologies appears to be necessary to initiate and propel disease forward to widespread circuits. Recent multidisciplinary findings strongly suggest that the third factor required for disease progression is an aberrant microglial immune response. This response may initially be beneficial; however, a maladaptive microglial response eventually develops, fueling a feed-forward spread of tau and Aβ pathology.]]>
Wed, 07 Oct 2015 00:00:00 PDT
Epigenomics and the structure of the living genome. Friedman N, Rando OJ
Genome Res (Oct 2015)

Eukaryotic genomes are packaged into an extensively folded state known as chromatin. Analysis of the structure of eukaryotic chromosomes has been revolutionized by development of a suite of genome-wide measurement technologies, collectively termed "epigenomics." We review major advances in epigenomic analysis of eukaryotic genomes, covering aspects of genome folding at scales ranging from whole chromosome folding down to nucleotide-resolution assays that provide structural insights into protein-DNA interactions. We then briefly outline several challenges remaining and highlight new developments such as single-cell epigenomic assays that will help provide us with a high-resolution structural understanding of eukaryotic genomes.]]>
Fri, 02 Oct 2015 00:00:00 PDT
Genomic imprinting in the human placenta. Monk D
Am J Obstet Gynecol (Oct 2015)

With the launch of the National Institute of Child Health and Human Development/National Institutes of Health Human Placenta Project, the anticipation is that this often-overlooked organ will be the subject of much intense research. Compared with somatic tissues, the cells of the placenta have a unique epigenetic profile that dictates its transcription patterns, which when disturbed may be associated with adverse pregnancy outcomes. One major class of genes that is dependent on strict epigenetic regulation in the placenta is subject to genomic imprinting, the parent-of-origin-dependent monoallelic gene expression. This review discusses the differences in allelic expression and epigenetic profiles of imprinted genes that are identified between different species, which reflect the continuous evolutionary adaption of this form of epigenetic regulation. These observations divulge that placenta-specific imprinted gene that is reliant on repressive histone signatures in mice are unlikely to be imprinted in humans, whereas intense methylation profiling in humans has uncovered numerous maternally methylated regions that are restricted to the placenta that are not conserved in mice. Imprinting has been proposed to be a mechanism that regulates parental resource allocation and ultimately can influence fetal growth, with the placenta being the key in this process. Furthermore, I discuss the developmental dynamics of both classic and transient placenta-specific imprinting and examine the evidence for an involvement of these genes in intrauterine growth restriction and placenta-associated complications. Finally, I focus on examples of genes that are regulated aberrantly in complicated pregnancies, emphasizing their application as pregnancy-related disease biomarkers to aid the diagnosis of at-risk pregnancies early in gestation.]]>
Fri, 02 Oct 2015 00:00:00 PDT
Exercise genomics-a paradigm shift is needed: a commentary. Bouchard C
Br J Sports Med (Oct 2015)

The overarching goal of exercise genomics is to illuminate exercise biology and behaviour in order to better understand the preventive and therapeutic values of exercise. An ancillary aim is to understand the role of genomic variation in human physical attributes and sports performance. The aim of this report is to briefly comment on the current status of exercise genetics and genomics and to suggest potential improvements to the research agenda and translational activities. First, the genomic features of interest to the biology of exercise are defined. Then, the limit of the current focus on common variants and their implications for exercise genomics is highlighted. The need for a major paradigm shift in exercise genomics research is discussed with an emphasis on study designs and appropriately powered studies as well as on more mechanistic and functional research. Finally, a summary of current practices in translational activities compared with what best practice demands is introduced. One suggestion is that the research portfolio of exercise genomics be composed of a larger fraction of experimental and mechanistic investigations and a smaller fraction of observational studies. It is also recommended that research should shift to unbiased exploration of the genome using all the power of genomics, epigenomics and transcriptomics in combination with large observational but preferably experimental study designs, including Mendelian randomisation. In all cases, emphasis on replications is of paramount importance. This represents an extraordinary challenge that can only be met with large-scale collaborative and multicentre research programmes.]]>
Fri, 02 Oct 2015 00:00:00 PDT
Mobile DNA Elements: The Seeds of Organic Complexity on Earth. Habibi L, Pedram M, AmirPhirozy A, Bonyadi K
DNA Cell Biol (Oct 2015)

Mobile DNA or transposable elements (TEs) are genomic sequences capable of moving themselves independently into different parts of the genome. Viral invasion of eukaryotic genomes is assumed to be the main source of TEs. Selfish transposition of these elements could be a serious threat to the host cell, as they can insert themselves into the middle of coding genes and/or induce genomic instability. In response, through millions of years of evolution, cells have come up with various mechanisms such as genomic imprinting, DNA methylation, heterochromatin formation, and RNA interference to deactivate them. Interestingly, these processes have also greatly contributed to important cellular functions involved in cell differentiation, development, and differential gene expression. Propagation of TE copies during the course of evolution have resulted in increasing the genome size and providing proper space and flexibility in shaping the genome by creating new genes and establishing essential cellular structures such as heterochromatin, centromere, and telomeres. Yet, these elements are mostly labeled for playing a role in pathogenesis of human diseases. Here, we attempt to introduce TEs as factors necessary for making us human rather than just selfish sequences or obligatory guests invading our DNA.]]>
Fri, 02 Oct 2015 00:00:00 PDT
Chromatin state analysis of the barley epigenome reveals a higher-order structure defined by H3K27me1 and H3K27me3 abundance. Baker K, Dhillon T, Colas I, Cook N, Milne I, Milne L, Bayer M, Flavell AJ
Plant J (Oct 2015)

Combinations of histones carrying different covalent modifications are a major component of epigenetic variation. We have mapped nine modified histones in the barley seedling epigenome by chromatin immunoprecipitation next-generation sequencing (ChIP-seq). The chromosomal distributions of the modifications group them into four different classes, and members of a given class also tend to coincide at the local DNA level, suggesting that global distribution patterns reflect local epigenetic environments. We used this peak sharing to define 10 chromatin states representing local epigenetic environments in the barley genome. Five states map mainly to genes and five to intergenic regions. Two genic states involving H3K36me3 are preferentially associated with constitutive gene expression, while an H3K27me3-containing genic state is associated with differentially expressed genes. The 10 states display striking distribution patterns that divide barley chromosomes into three distinct global environments. First, telomere-proximal regions contain high densities of H3K27me3 covering both genes and intergenic DNA, together with very low levels of the repressive H3K27me1 modification. Flanking these are gene-rich interior regions that are rich in active chromatin states and have greatly decreased levels of H3K27me3 and increasing amounts of H3K27me1 and H3K9me2. Lastly, H3K27me3-depleted pericentromeric regions contain gene islands with active chromatin states separated by extensive retrotransposon-rich regions that are associated with abundant H3K27me1 and H3K9me2 modifications. We propose an epigenomic framework for barley whereby intergenic H3K27me3 specifies facultative heterochromatin in the telomere-proximal regions and H3K27me1 is diagnostic for constitutive heterochromatin elsewhere in the barley genome.]]>
Thu, 01 Oct 2015 00:00:00 PDT
[Progress in research on imprinted gene associated with male infertility]. Wang W, Wang R, Liu R
Zhonghua Yi Xue Yi Chuan Xue Za Zhi (Oct 2015)

The connection between male infertility and abnormal methylation of imprinted genes has attracted much attention. Some imprinted genes, e.g., H19, MEG3, MEST and SNRPN, are known to be related with male infertility. Abnormal imprinted information may influence sperm concentration, motility and morphology, but the mechanism is still unclear. Sperm genomic imprinting reconstruction and erase respectively occur at the time of spermatogenesis and before embryo transfer. Many studies have shown that the probability of imprinting disorder syndrome of offspring born through assisted reproductive technology (ART) was significantly higher, leading to the worry about the safety of ART and speculation that the operation and in vitro environment may affect sperm imprinted information, which in turn may lead to imprinting diseases in the offspring. However, above connection still lacks convincing evidence. This paper has conducted a literature review of recent literature and explored the impact of abnormal methylation of imprinted genes on male fertility and the offspring.]]>
Wed, 30 Sep 2015 00:00:00 PDT
methylPipe and compEpiTools: a suite of R packages for the integrative analysis of epigenomics data. Kishore K, de Pretis S, Lister R, Morelli MJ, Bianchi V, Amati B, Ecker JR, Pelizzola M
BMC Bioinformatics (2015)

Numerous methods are available to profile several epigenetic marks, providing data with different genome coverage and resolution. Large epigenomic datasets are then generated, and often combined with other high-throughput data, including RNA-seq, ChIP-seq for transcription factors (TFs) binding and DNase-seq experiments. Despite the numerous computational tools covering specific steps in the analysis of large-scale epigenomics data, comprehensive software solutions for their integrative analysis are still missing. Multiple tools must be identified and combined to jointly analyze histone marks, TFs binding and other -omics data together with DNA methylation data, complicating the analysis of these data and their integration with publicly available datasets.]]>
Tue, 29 Sep 2015 00:00:00 PDT
Long noncoding RNAs in human disease: emerging mechanisms and therapeutic strategies. Lalevée S, Feil R
Epigenomics (Sep 2015)

Tue, 29 Sep 2015 00:00:00 PDT
De novo DNA methylation through 5'-segment of the H19 ICR maintains its imprint during early embryogenesis. Matsuzaki H, Okamura E, Takahashi T, Ushiki A, Nakamura T, Nakano T, Hata K, Fukamizu A, Tanimoto K
Development (Sep 2015)

Genomic imprinting is a major monoallelic gene expression regulatory mechanism in mammals, and depends on gamete-specific DNA methylation of specialized cis-regulatory elements called imprinting control regions (ICRs). Allele-specific DNA methylation of the ICRs is faithfully maintained at the imprinted loci throughout development, even in early embryos where genomes undergo extensive epigenetic reprogramming, including DNA demethylation, to acquire totipotency. We previously found that an ectopically introduced H19 ICR fragment in transgenic mice acquired paternal allele-specific methylation in the somatic cells of offspring, while it was not methylated in sperm, suggesting its gametic and postfertilization modifications are separable events. We hypothesized that this latter activity might contribute to maintenance of the methylation imprint in early embryos. Here we demonstrate that methylation of the paternally inherited transgenic H19 ICR commences soon after fertilization in a maternal Dnmt3a- and Dnmt3L-dependent manner. When its germline methylation was partially obstructed by insertion of insulator sequences, the endogenous, paternal H19 ICR also exhibited postfertilization methylation. Finally, we refined the responsible sequences for this activity in transgenic mice, and found that deletion of the 5' segment of the endogenous paternal H19 ICR decreased its methylation after fertilization, attenuated Igf2 gene expression. These results demonstrate that this segment of the H19 ICR is essential for its de novo post-fertilization DNA methylation, and that this activity contributes to the maintenance of imprinted methylation at the endogenous H19 ICR during early embryogenesis.]]>
Tue, 29 Sep 2015 00:00:00 PDT
Development of novel tools for the in vitro investigation of drug-induced liver injury. Jiang J, Wolters JE, van Breda SG, Kleinjans JC, de Kok TM
Expert Opin Drug Metab Toxicol (Oct 2015)

Due to its complex mechanisms and unpredictable occurrence, drug-induced liver injury (DILI) complicates drug identification and classification. Since species-specific differences in metabolism and pharmacokinetics exist, data obtained from animal studies may not be sufficient to predict DILI in humans.]]>
Sat, 19 Sep 2015 00:00:00 PDT
Derivation of a Homozygous Human Androgenetic Embryonic Stem Cell Line. Ding C, Huang S, Qi Q, Fu R, Zhu W, Cai B, Hong P, Liu Z, Gu T, Zeng Y, Wang J, Xu Y, Zhao X, Zhou Q, Zhou C
Stem Cells Dev (Oct 2015)

Human embryonic stem cells (hESCs) have long been considered as a promising source for cell replacement therapy. However, one major obstacle for the use of these cells is immune compatibility. Histocompatible human parthenogenetic ESCs have been reported as a new method for generating human leukocyte antigen (HLA)-matched hESCs. To further investigate the possibility of obtaining histocompatible stem cells from uniparental embryos, we tried to produce androgenetic haploid human embryos by injecting a single spermatozoon into enucleated human oocyte, and establish human androgenetic embryonic stem (hAGES) cell lines from androgenetic embryos. In the present study, a diploid hAGES cell line has been established, which exhibits typical features of human ESCs, including the expression of pluripotency markers, having differentiation potential in vitro and in vivo, and stable propagation in an undifferentiated state (>P40). Bisulfite sequencing of the H19, Snrpn, Meg3, and Kv imprinting control regions suggested that hAGES cells maintained to a certain extent a sperm methylation pattern. Genome-wide single nucleotide polymorphism, short tandem repeat, and HLA analyses revealed that the hAGES cell genome was highly homozygous. These results suggest that hAGES cells from spermatozoon could serve as a useful tool for studying the mechanisms underlying genomic imprinting in humans. It might also be used as a potential resource for cell replacement therapy as parthenogenetic stem cells.]]>
Sat, 19 Sep 2015 00:00:00 PDT
The Role of Epigenetics in the Latent Effects of Early Life Exposure to Obesogenic Endocrine Disrupting Chemicals. Stel J, Legler J
Endocrinology (Oct 2015)

Recent research supports a role for exposure to endocrine-disrupting chemicals (EDCs) in the global obesity epidemic. Obesogenic EDCs have the potential to inappropriately stimulate adipogenesis and fat storage, influence metabolism and energy balance and increase susceptibility to obesity. Developmental exposure to obesogenic EDCs is proposed to interfere with epigenetic programming of gene regulation, partly by activation of nuclear receptors, thereby influencing the risk of obesity later in life. The goal of this minireview is to briefly describe the epigenetic mechanisms underlying developmental plasticity and to evaluate the evidence of a mechanistic link between altered epigenetic gene regulation by early life EDC exposure and latent onset of obesity. We summarize the results of recent in vitro, in vivo, and transgenerational studies, which clearly show that the obesogenic effects of EDCs such as tributyltin, brominated diphenyl ether 47, and polycyclic aromatic hydrocarbons are mediated by the activation and associated altered methylation of peroxisome proliferator-activated receptor-γ, the master regulator of adipogenesis, or its target genes. Importantly, studies are emerging that assess the effects of EDCs on the interplay between DNA methylation and histone modifications in altered chromatin structure. These types of studies coupled with genome-wide rather than gene-specific analyses are needed to improve mechanistic understanding of epigenetic changes by EDC exposure. Current advances in the field of epigenomics have led to the first potential epigenetic markers for obesity that can be detected at birth, providing an important basis to determine the effects of developmental exposure to obesogenic EDCs in humans.]]>
Sat, 19 Sep 2015 00:00:00 PDT
Age and Obesity Promote Methylation and Suppression of 5α-Reductase 2: Implications for Personalized Therapy of Benign Prostatic Hyperplasia. Bechis SK, Otsetov AG, Ge R, Wang Z, Vangel MG, Wu CL, Tabatabaei S, Olumi AF
J Urol (Oct 2015)

In men with symptomatic benign prostatic hyperplasia 5α-reductase inhibitors are a main modality of treatment. More than 30% of men do not respond to the therapeutic effects of 5α-reductase inhibitors. We have found that a third of adult prostate samples do not express 5α-reductase type 2 secondary to epigenetic modifications. We evaluated whether 5α-reductase type 2 expression in benign prostatic hyperplasia specimens from symptomatic men was linked to methylation of the 5α-reductase type 2 gene promoter. We also identified associations with age, obesity, cardiac risk factors and prostate specific antigen.]]>
Sat, 19 Sep 2015 00:00:00 PDT
Genomic imprinting: A missing piece of the Multiple Sclerosis puzzle? Ruhrmann S, Stridh P, Kular L, Jagodic M
Int J Biochem Cell Biol (Oct 2015)

Evidence for parent-of-origin effects in complex diseases such as Multiple Sclerosis (MS) strongly suggests a role for epigenetic mechanisms in their pathogenesis. In this review, we describe the importance of accounting for parent-of-origin when identifying new risk variants for complex diseases and discuss how genomic imprinting, one of the best-characterized epigenetic mechanisms causing parent-of-origin effects, may impact etiology of complex diseases. While the role of imprinted genes in growth and development is well established, the contribution and molecular mechanisms underlying the impact of genomic imprinting in immune functions and inflammatory diseases are still largely unknown. Here we discuss emerging roles of imprinted genes in the regulation of inflammatory responses with a particular focus on the Dlk1 cluster that has been implicated in etiology of experimental MS-like disease and Type 1 Diabetes. Moreover, we speculate on the potential wider impact of imprinting via the action of imprinted microRNAs, which are abundantly present in the Dlk1 locus and predicted to fine-tune important immune functions. Finally, we reflect on how unrelated imprinted genes or imprinted genes together with non-imprinted genes can interact in so-called imprinted gene networks (IGN) and suggest that IGNs could partly explain observed parent-of-origin effects in complex diseases. Unveiling the mechanisms of parent-of-origin effects is therefore likely to teach us not only about the etiology of complex diseases but also about the unknown roles of this fascinating phenomenon underlying uneven genetic contribution from our parents. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease.]]>
Wed, 09 Sep 2015 00:00:00 PDT
Chromatin mechanisms in the developmental control of imprinted gene expression. Sanli I, Feil R
Int J Biochem Cell Biol (Oct 2015)

Hundreds of protein-coding genes and regulatory non-coding RNAs (ncRNAs) are subject to genomic imprinting. The mono-allelic DNA methylation marks that control imprinted gene expression are somatically maintained throughout development, and this process is linked to specific chromatin features. Yet, at many imprinted genes, the mono-allelic expression is lineage or tissue-specific. Recent studies provide mechanistic insights into the developmentally-restricted action of the 'imprinting control regions' (ICRs). At several imprinted domains, the ICR expresses a long ncRNA that mediates chromatin repression in cis (and probably in trans as well). ICRs at other imprinted domains mediate higher-order chromatin structuration that enhances, or prevents, transcription of close-by genes. Here, we present how chromatin and ncRNAs contribute to developmental control of imprinted gene expression and discuss implications for disease. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease.]]>
Wed, 09 Sep 2015 00:00:00 PDT