'; ?> 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, 18 Jun 2013 18:38:08 PDT Tue, 18 Jun 2013 18:38:08 PDT jirtle@radonc.duke.edu james001@jirtle.com RNA-directed DNA methylation regulates parental genomic imprinting at several loci in Arabidopsis. Vu TM, Nakamura M, Calarco JP, Susaki D, Lim PQ, Kinoshita T, Higashiyama T, Martienssen RA, Berger F
Development (Jun 2013)

In mammals and plants, parental genomic imprinting restricts the expression of specific loci to one parental allele. Imprinting in mammals relies on sex-dependent de novo deposition of DNA methylation during gametogenesis but a comparable mechanism was not shown in plants. Rather, paternal silencing by the maintenance DNA methyltransferase 1 (MET1) and maternal activation by the DNA demethylase DEMETER (DME) cause maternal expression. However, genome-wide studies suggested other DNA methylation-dependent imprinting mechanisms. Here, we show that de novo RNA-directed DNA methylation (RdDM) regulates imprinting at specific loci expressed in endosperm. RdDM in somatic tissues is required to silence expression of the paternal allele. By contrast, the repression of RdDM in female gametes participates with or without DME requirement in the activation of the maternal allele. The contrasted activity of DNA methylation between male and female gametes appears sufficient to prime imprinted maternal expression. After fertilization, MET1 maintains differential expression between the parental alleles. RdDM depends on small interfering RNAs (siRNAs). The involvement of RdDM in imprinting supports the idea that sources of siRNAs such as transposons and de novo DNA methylation were recruited in a convergent manner in plants and mammals in the evolutionary process leading to selection of imprinted loci.]]> Thu, 13 Jun 2013 00:00:00 PDT Epigenetics and phenotypic variability: some interesting insights from birds. Frésard L, Morisson M, Brun JM, Collin A, Pain B, Minvielle F, Pitel F
Genet Sel Evol (Jun 2013)

Little is known about epigenetic mechanisms in birds with the exception of the phenomenon of dosage compensation of sex chromosomes, although such mechanisms could be involved in the phenotypic variability of birds, as in several livestock species. This paper reviews the literature on epigenetic mechanisms that could contribute significantly to trait variability in birds, and compares the results to the existing knowledge of epigenetic mechanisms in mammals. The main issues addressed in this paper are: (1) Does genomic imprinting exist in birds? (2) How does the embryonic environment influence the adult phenotype in avian species? (3) Does the embryonic environment have an impact on phenotypic variability across several successive generations? The potential for epigenetic studies to improve the performance of individual animals through the implementation of limited changes in breeding conditions or the addition of new parameters in selection models is still an open question.]]> Thu, 13 Jun 2013 00:00:00 PDT Conversion of genomic imprinting by reprogramming and redifferentiation. Kim MJ, Choi HW, Jang HJ, Chung HM, Arauzo-Bravo MJ, Schöler HR, Do JT
J Cell Sci (Jun 2013)

Induced pluripotent stem cells (iPSCs), generated from somatic cells by overexpression of transcription factors Oct4, Sox2, Klf4 and c-Myc have the same characteristics as pluripotent embryonic stem cells (ESCs). iPSCs reprogrammed from differentiated cells undergo epigenetic modification during reprogramming, and ultimately acquire a similar epigenetic state to that of ESCs. In this study, these epigenetic changes were observed in reprogramming of uniparental parthenogenetic somatic cells. The parthenogenetic pattern of imprinted genes changes during the generation of parthenogenetic maternal iPSCs (miPSCs), a process referred to as pluripotent reprogramming. We determined whether altered imprinted genes are maintained or revert to the parthenogenetic state when the reprogrammed cells are redifferentiated into specialized cell types. To address this question, we redifferentiated miPSCs into neural stem cells (miPS-NSCs) and compared them with biparental female NSCs (fNSCs) and parthenogenetic NSCs (pNSCs). We found that pluripotent reprogramming of parthenogenetic somatic cells could reset parthenogenetic DNA methylation patterns in imprinted genes, and that alterations in DNA methylation were maintained even after miPSCs were redifferentiated into miPS-NSCs. Notably, maternally methylated imprinted genes (Peg1, Peg3, Igf2r, Snrpn and Ndn), whose differentially methylated regions were fully methylated in pNSCs, were demethylated and their expression levels were found to be close to the levels in normal biparental fNSCs after reprogramming and redifferentiation. Our findings suggest that pluripotent reprogramming of parthenogenetic somatic cells followed by redifferentiation leads to changes in DNA methylation of imprinted genes and the reestablishment of gene expression levels to those of normal biparental cells.]]> Thu, 13 Jun 2013 00:00:00 PDT Research Highlights: Highlights from the latest articles in epigenomics. Jazirehi AR, Torres-Collado AX, Nazarian R
Epigenomics (Jun 2013)

]]> Tue, 11 Jun 2013 00:00:00 PDT News & views in ... Epigenomics.
Epigenomics (Jun 2013)

]]> Tue, 11 Jun 2013 00:00:00 PDT Paternally expressed genes predominate in the placenta. Wang X, Miller DC, Harman R, Antczak DF, Clark AG
Proc Natl Acad Sci U S A (Jun 2013)

The discovery of genomic imprinting through studies of manipulated mouse embryos indicated that the paternal genome has a major influence on placental development. However, previous research has not demonstrated paternal bias in imprinted genes. We applied RNA sequencing to trophoblast tissue from reciprocal hybrids of horse and donkey, where genotypic differences allowed parent-of-origin identification of most expressed genes. Using this approach, we identified a core group of 15 ancient imprinted genes, of which 10 were paternally expressed. An additional 78 candidate imprinted genes identified by RNA sequencing also showed paternal bias. Pyrosequencing was used to confirm the imprinting status of six of the genes, including the insulin receptor (INSR), which may play a role in growth regulation with its reciprocally imprinted ligand, histone acetyltransferase-1 (HAT1), a gene involved in chromatin modification, and lymphocyte antigen 6 complex, locus G6C, a newly identified imprinted gene in the major histocompatibility complex. The 78 candidate imprinted genes displayed parent-of-origin expression bias in placenta but not fetus, and most showed less than 100% silencing of the imprinted allele. Some displayed variability in imprinting status among individuals. This variability results in a unique epigenetic signature for each placenta that contributes to variation in the intrauterine environment and thus presents the opportunity for natural selection to operate on parent-of-origin differential regulation. Taken together, these features highlight the plasticity of imprinting in mammals and the central importance of the placenta as a target tissue for genomic imprinting.]]> Tue, 11 Jun 2013 00:00:00 PDT Genes, assisted reproductive technology and trans-illumination. Dias RP, Maher ER
Epigenomics (Jun 2013)

Genomic imprinting is a parent-of-origin allele-specific epigenetic process that is critical for normal development and health. The establishment and maintenance of normal imprinting is dependent on both cis-acting imprinting control centers, which are marked by differentially (parental allele specific) methylated marks, and trans mechanisms, which regulate the establishment and/or maintenance of the correct methylation epigenotype at the imprinting control centers. Studies of rare human imprinting disorders such as familial hydatidiform mole, Beckwith-Wiedemann syndrome and familial transient neonatal diabetes mellitus have enabled the identification of genetic (e.g., mutations in KHDC3L [C6ORF221], NLRP2 [NALP2], NLRP7 [NALP7] and ZFP57) and environmental (assisted reproductive technologies) factors that can disturb the normal trans mechanisms for imprinting establishment and/or maintenance. Here we review the clinical and molecular aspects of these imprinting disorders in order to demonstrate how the study of rare inherited disorders can illuminate the molecular characteristics of fundamental epigenetic processes, such as genomic imprinting.]]> Tue, 11 Jun 2013 00:00:00 PDT Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation. Herceg Z, Lambert MP, van Veldhoven K, Demetriou C, Vineis P, Smith MT, Straif K, Wild CP
Carcinogenesis (Jun 2013)

Remarkable progress in the field of epigenetics has turned academic, medical and public attention to the potential applications of these new advances in medicine and biomedical research. The result is a broader appreciation of epigenetic phenomena in the etiology of common human diseases, notably cancer. These advances represent an exciting opportunity to incorporate epigenetics and epigenomics into carcinogen identification and safety assessment. Current epigenetic studies, including major international sequencing projects, should generate information establishing the "normal" epigenome of tissues and cell types as well as the physiological variability of the epigenome against which carcinogen exposure can be assessed. Despite epigenetic events emerging as key mechanisms in cancer development, our search of the Monograph Volume 100 revealed that the use of epigenetic data in evaluating human carcinogens by the International Agency for Research on Cancer (IARC) Monographs has been modest so far. Here, we review (i) the current status of epigenetics incorporation in carcinogen evaluation in the IARC Monographs Programme, (ii) potential modes of action for epigenetic carcinogens, (iii) current in vivo and in vitro technologies to detect epigenetic carcinogens, (iv) genomic regions and epigenetic modifications and their biological consequences, (v) critical technological and biological issues in assessing epigenetic carcinogens. We also discuss issues related to opportunities and challenges in applying epigenetic testing in carcinogen identification and evaluation. Although epigenetic assays are just beginning to be applied in carcinogen evaluation, important data are being generated and valuable scientific resources are being established that should catalyze future applications of epigenetic testing.]]> Mon, 10 Jun 2013 00:00:00 PDT Overview of high throughput sequencing technologies to elucidate molecular pathways in cardiovascular diseases. Churko JM, Mantalas GL, Snyder MP, Wu JC
Circ Res (Jun 2013)

High throughput sequencing technologies have become essential in studies on genomics, epigenomics, and transcriptomics. Although sequencing information has traditionally been elucidated using a low throughput technique called Sanger sequencing, high throughput sequencing technologies are capable of sequencing multiple DNA molecules in parallel, enabling hundreds of millions of DNA molecules to be sequenced at a time. This advantage allows high throughput sequencing to be used to create large data sets, generating more comprehensive insights into the cellular genomic and transcriptomic signatures of various diseases and developmental stages. Within high throughput sequencing technologies, whole exome sequencing can be used to identify novel variants and other mutations that may underlie many genetic cardiac disorders, whereas RNA sequencing can be used to analyze how the transcriptome changes. Chromatin immunoprecipitation sequencing and methylation sequencing can be used to identify epigenetic changes, whereas ribosome sequencing can be used to determine which mRNA transcripts are actively being translated. In this review, we will outline the differences in various sequencing modalities and examine the main sequencing platforms on the market in terms of their relative read depths, speeds, and costs. Finally, we will discuss the development of future sequencing platforms and how these new technologies may improve on current sequencing platforms. Ultimately, these sequencing technologies will be instrumental in further delineating how the cardiovascular system develops and how perturbations in DNA and RNA can lead to cardiovascular disease.]]> Fri, 07 Jun 2013 00:00:00 PDT Aberrant methylation of multiple imprinted genes in embryos of tamoxifen treated male rats. Kedia-Mokashi NA, Kadam L, Ankolkar M, Dumasia K, Balasinor NH
Reproduction (Jun 2013)

Genomic imprinting is an epigenetic phenomenon known to regulate fetal growth and development. Studies from our laboratory have demonstrated that treatment of adult male rats with tamoxifen increased post-implantation loss at around mid gestation. Further studies demonstrated aberrant expression of transcripts of multiple imprinted genes in the resorbing embryos at days 11 and 13 of gestation including insulin like growth factor 2. In addition, decrease in methylation at the Igf2-H19 imprint control region was observed in spermatozoa and in resorbing embryos sired by tamoxifen treated males. In the present study, methylation analysis of the imprinted genes, which were found to be differentially expressed, was done using EpiTYPER in the spermatozoa of tamoxifen treated rats and post-implantation embryos sired by tamoxifen treated rats. Differentially methylated regions for most imprinted genes have not been identified in the rat. Hence initial experiments were done to identify the putative differentially methylated regions in the genes selected for the study. Increased methylation at CpG islands present in the putative differentially methylated regions of number of imprinted genes was observed in the resorbing embryos sired by tamoxifen treated male rats. This increase in methylation is in agreement with the down-regulation of most of these genes at the transcript level in the resorbing embryos. No change in the methylation status of these genes was observed in spermatozoa. The study suggests deregulation of mechanisms protecting unmethylated allele from wave of de-novo methylation occurring following implantation.]]> Thu, 06 Jun 2013 00:00:00 PDT Cancer control and prevention: nutrition and epigenetics. Verma M
Curr Opin Clin Nutr Metab Care (Jul 2013)

To evaluate recent developments in nutritional epigenomics and related challenges, opportunities, and implications for cancer control and prevention.]]> Thu, 06 Jun 2013 00:00:00 PDT Epigenome-wide inheritance of cytosine methylation variants in a recombinant inbred population. Schmitz RJ, He Y, Valdés-López O, Khan SM, Joshi T, Urich MA, Nery JR, Diers B, Xu D, Stacey G, Ecker JR
Genome Res (Jun 2013)

Cytosine DNA methylation is one avenue for passing information through cell divisions. Here, we present epigenomic analyses of soybean recombinant inbred lines (RILs) and their parents. Identification of differentially methylated regions (DMRs) revealed DMRs mostly co-segregated with the genotype from which they were derived, but examples of uncoupling of genotype and epigenotype were identified. Linkage mapping of methylation states assessed from whole-genome bisulfite sequencing of 83 RILs uncovered widespread evidence for local methylQTL. This epigenomics approach provides a comprehensive study of the patterns and heritability of methylation variants in a complex genetic population over multiple generations paving the way for understanding how methylation variants contribute to phenotypic variation.]]> Thu, 06 Jun 2013 00:00:00 PDT NGS++: a library for rapid prototyping of epigenomics software tools. Nordell Markovits A, Joly Beauparlant C, Toupin D, Wang S, Droit A, Gevry N
Bioinformatics (Jun 2013)

MOTIVATION: The development of computational tools to enable testing and analysis of high throughput-sequencing data is essential to modern genomics research. However, while multiple frameworks have been developed to facilitate access to these tools, comparatively little effort has been made at implementing low level programming libraries to increase the speed and ease of their development. RESULTS: We propose NGS++, a programming library in C++11 specialized in manipulating both Next-Generation Sequencing (NGS) datasets and genomic information files. This library allows easy integration of new formats and rapid prototyping of new functionalities with a focus on the analysis of genomic regions and features. It offers a powerful, yet versatile and easily extensible interface to read, write and manipulate multiple genomic file formats. By standardizing the internal data structures and presenting a common interface to the data parser, NGS++ offers an effective framework for epigenomics tool development. AVAILABILITY: NGS++ was written in C++ using the C++11 standard. It requires minimal efforts to build and is well-documented via a complete docXygen guide, online documentation and tutorials. Source code, tests, code examples and documentation are available via the website at http://www.ngsplusplus.ca and the github repository at https://github.com/NGS-lib/NGSplusplus. CONTACT: nicolas.gevry@usherbrooke.ca, arnaud.droit@crchuq.ulaval.ca.]]> Wed, 05 Jun 2013 00:00:00 PDT Postnatal epigenetic reprogramming in the germline of a marsupial, the tammar wallaby. Suzuki S, Shaw G, Renfree MB
Epigenetics Chromatin (Jun 2013)

BACKGROUND: Epigenetic reprogramming is essential to restore totipotency and to reset genomic imprints during mammalian germ cell development and gamete formation. The dynamic DNA methylation change at DMRs (differentially methylated regions) within imprinted domains and of retrotransposons is characteristic of this process. Both marsupials and eutherian mammals have genomic imprinting but these two subgroups have been evolving separately for up to 160 million years. Marsupials have a unique reproductive strategy and deliver tiny, altricial young that complete their development within their mother's pouch. Germ cell proliferation in the genital ridge continues after birth in the tammar wallaby (Macropus eugenii), and it is only after 25 days postpartum that female germ cells begin to enter meiosis and male germ cells begin to enter mitotic arrest. At least two marsupial imprinted loci (PEG10 and H19) also have DMRs. To investigate the evolution of epigenetic reprogramming in the marsupial germline, here we collected germ cells from male pouch young of the tammar wallaby and analysed the methylation status of PEG10 and H19 DMR, an LTR (long terminal repeat) and a non-LTR retrotransposons. RESULTS: Demethylation of the H19 DMR was almost completed by 14 days postpartum and de-novo methylation started from 34 days postpartum. These stages correspond to 14 days after the completion of primordial germ cell migration into genital ridge (demethylation) and 9 days after the first detection of mitotic arrest (re-methylation) in the male germ cells. Interestingly, the PEG10 DMR was already unmethylated at 7 days postpartum, suggesting that the timing of epigenetic reprogramming is not the same at all genomic loci. Retrotransposon methylation was not completely removed after the demethylation event in the germ cells, similar to the situation in the mouse. CONCLUSIONS: Thus, despite the postnatal occurrence of epigenetic reprogramming and the persistence of genome-wide undermethylation for 20 days in the postnatal tammar, the relative timing and mechanism of germ cell reprogramming are conserved between marsupials and eutherians. We suggest that the basic mechanism of epigenetic reprogramming had already been established before the marsupial-eutherian split and has been faithfully maintained for at least 160 million years and may reflect the timing of the onset of mitotic arrest in the male germline.]]> Tue, 04 Jun 2013 00:00:00 PDT Folate and fetal programming: a play in epigenomics? Guéant JL, Namour F, Guéant-Rodriguez RM, Daval JL
Trends Endocrinol Metab (Jun 2013)

Folate plays a key role in the interactions between nutrition, fetal programming, and epigenomics. Maternal folate status influences DNA methylation, inheritance of the agouti phenotype, expression of imprinting genes, and the effects of mycotoxin FB1 on heterochromatin assembly in rodent offspring. Deficiency in folate and other methyl donors increases birth defects and produces visceral manifestations of fetal programming, including liver and heart steatosis, through imbalanced methylation and acetylation of PGC1-α and decreased SIRT1 expression, and produces persistent cognitive and learning disabilities through impaired plasticity and hippocampal atrophy. Maternal folate supplementation also produces long-term epigenomic effects in offspring, some beneficial and others negative. Deciphering these mechanisms will help understanding the discordances between experimental models and population studies of folate deficiency and supplementation.]]> Fri, 31 May 2013 00:00:00 PDT Epigenetic regulation of placental endocrine lineages and complications of pregnancy. John RM
Biochem Soc Trans (Jun 2013)

A defining feature of mammals is the development in utero of the fetus supported by the constant flow of nutrients from the mother obtained via a specialized organ: the placenta. The placenta is also a major endocrine organ that synthesizes vast quantities of hormones and cytokines to instruct both maternal and fetal physiology. Nearly 20 years ago, David Haig and colleagues proposed that placental hormones were likely targets of the epigenetic process of genomic imprinting in response to the genetic conflicts imposed by in utero development [Haig (1993) Q. Rev. Biol. 68, 495-532]. There are two simple mechanisms through which genomic imprinting could regulate placental hormones. First, imprints could directly switch on or off alleles of specific genes. Secondly, imprinted genes could alter the expression of placental hormones by regulating the development of placental endocrine lineages. In mice, the placental hormones are synthesized in the trophoblast giant cells and spongiotrophoblast cells of the mature placenta. In the present article, I review the functional role of imprinted genes in regulating these endocrine lineages, which lends support to Haig's original hypothesis. I also discuss how imprinting defects in the placenta may adversely affect the health of the fetus and its mother during pregnancy and beyond.]]> Thu, 23 May 2013 00:00:00 PDT The role of imprinted genes in humans. Ishida M, Moore GE
Mol Aspects Med ()

Genomic imprinting, a process of epigenetic modification which allows the gene to be expressed in a parent-of-origin specific manner, has an essential role in normal growth and development. Imprinting is found predominantly in placental mammals, and has potentially evolved as a mechanism to balance parental resource allocation to the offspring. Therefore, genetic and epigenetic disruptions which alter the specific dosage of imprinted genes can lead to various developmental abnormalities often associated with fetal growth and neurological behaviour. Over the past 20years since the first imprinted gene was discovered, many different mechanisms have been implicated in this special regulatory mode of gene expression. This review includes a brief summary of the current understanding of the key molecular events taking place during imprint establishment and maintenance in early embryos, and their relationship to epigenetic disruptions seen in imprinting disorders. Genetic and epigenetic causes of eight recognised imprinting disorders including Silver-Russell syndrome (SRS) and Beckwith-Wiedemann syndrome (BWS), and also their association with Assisted reproductive technology (ART) will be discussed. Finally, the role of imprinted genes in fetal growth will be explored by investigating their relationship to a common growth disorder, intrauterine growth restriction (IUGR) and also their potential role in regulating normal growth variation.]]> Mon, 20 May 2013 00:00:00 PDT The Battle of the Sexes over Seed Size: Support for Both Kinship Genomic Imprinting and Interlocus Contest Evolution. Willi Y
Am Nat (Jun 2013)

Abstract Outcrossing creates a venue for parental conflict. When one sex provides parental care to offspring fertilized by several partners, the nonproviding sex is under selection to maximally exploit the caring sex. The caring sex may counteradapt, and a coevolutionary arms race ensues. Genetic models of this conflict include the kinship theory of genomic imprinting (parent-of-origin-specific expression of maternal-care effectors) and interlocus conflict evolution (interaction between male selfish signals and female abatement). Predictions were tested by measuring the sizes of seeds produced by within-population crosses (diallel design) and between-population crosses in outcrossing and selfing populations of Arabidopsis lyrata. Within-population diallel crosses revealed substantial maternal variance in seed size in most populations. The comparison of between- and within-population crosses showed that seeds were larger when pollen came from another outcrossing population than when pollen came from a selfing or the same population, supporting interlocus contest evolution between male selfish genes and female recognition genes. Evidence for kinship genomic imprinting came from complementary trait means of seed size in reciprocal between-population crosses independent of whether populations were predominantly selfing or outcrossing. Hence, both kinship genomic imprinting and interlocus contest are supported in outcrossing Arabidopsis, whereas only kinship genomic imprinting is important in selfing populations.]]> Tue, 14 May 2013 00:00:00 PDT Genomic imprinting of the type 3 thyroid hormone deiodinase gene: Regulation and developmental implications. Charalambous M, Hernandez A
Biochim Biophys Acta (Jul 2013)

In recent years, findings in a number of animal and human models have ignited renewed interest in the type 3 deiodinase (D3), the main enzyme responsible for the inactivation of thyroid hormones. The induction of D3 in models of illness and injury has raised critical questions about the physiological significance of reduced thyroid hormone availability in those states. Phenotypes in transgenic mice lacking this enzyme also point to important developmental roles for D3. A critical determinant of D3 expression is genomic imprinting, an epigenetic phenomenon that regulates a small number of dosage-critical genes in the mammalian genome. The D3 gene (Dio3) is imprinted and preferentially expressed from one of the alleles in most tissues.]]> Wed, 08 May 2013 00:00:00 PDT Histone deacetylases as targets for treatment of multiple diseases. Tang J, Yan H, Zhuang S
Clin Sci (Lond) (Jun 2013)

HDACs (histone deacetylases) are a group of enzymes that deacetylate histones as well as non-histone proteins. They are known as modulators of gene transcription and are associated with proliferation and differentiation of a variety of cell types and the pathogenesis of some diseases. Recently, HDACs have come to be considered crucial targets in various diseases, including cancer, interstitial fibrosis, autoimmune and inflammatory diseases, and metabolic disorders. Pharmacological inhibitors of HDACs have been used or tested to treat those diseases. In the present review, we will examine the application of HDAC inhibitors in a variety of diseases with the focus on their effects of anti-cancer, fibrosis, anti-inflammatory, immunomodulatory activity and regulating metabolic disorders.]]> Mon, 18 Feb 2013 00:00:00 PST