'; ?> 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, 23 Feb 2017 00:24:38 PST Thu, 23 Feb 2017 00:24:38 PST jirtle@radonc.duke.edu james001@jirtle.com The causes and consequences of DNA methylome variation in plants. Seymour DK, Becker C
Curr Opin Plant Biol (Feb 2017)

Epigenetic variation - polymorphisms at the level of DNA methylation or histone modifications - modulates chromatin accessibility, which can perturb transcriptional activity and spur phenotypic variation. Determining the origin, frequency spectrum, and consequences of epigenetic variants is key to understanding the role of this variation in generating stable phenotypic variation in plants. Here we review recent literature on DNA methylation variation in both model and crop plant species with a focus on the link between genotype, epigenotype, and transcription. We highlight population epigenomics studies that explore the relationship between epigenetic variants and genetic diversity. Moreover, we provide an overview of relevant studies that together advocate a minor, albeit significant role for epigenetic variation in directing specific transcriptional changes.]]>
Wed, 22 Feb 2017 00:00:00 PST
Variable DAXX gene methylation is a common feature of placental trophoblast differentiation, preeclampsia, and response to hypoxia. Novakovic B, Evain-Brion D, Murthi P, Fournier T, Saffery R
FASEB J (Feb 2017)

Placental functioning relies on the appropriate differentiation of progenitor villous cytotrophoblasts (CTBs) into extravillous cytotrophoblasts (EVCTs), including invasive EVCTs, and the multinucleated syncytiotrophoblast (ST) layer. This is accompanied by a general move away from a proliferative, immature phenotype. Genome-scale expression studies have provided valuable insight into genes that are associated with the shift to both an invasive EVCT and ST phenotype, whereas genome-scale DNA methylation analysis has shown that differentiation to ST involves widespread methylation shifts, which are counteracted by low oxygen. In the current study, we sought to identify DNA methylation variation that is associated with transition from CTB to ST in vitro and from a noninvasive to invasive EVCT phenotype after culture on Matrigel. Of the several hundred differentially methylated regions that were identified in each comparison, the majority showed a loss of methylation with differentiation. This included a large differentially methylated region (DMR) in the gene body of death domain-associated protein 6 (DAXX ), which lost methylation during both CTB syncytialization to ST and EVCT differentiation to invasive EVCT. Comparison to publicly available methylation array data identified the same DMR as among the most consistently differentially methylated genes in placental samples from preeclampsia pregnancies. Of interest, in vitro culture of CTB or ST in low oxygen increases methylation in the same region, which correlates with delayed differentiation. Analysis of combined epigenomics signatures confirmed DAXX DMR as a likely regulatory element, and direct gene expression analysis identified a positive association between methylation at this site and DAXX expression levels. The widespread dynamic nature of DAXX methylation in association with trophoblast differentiation and placenta-associated pathologies is consistent with an important role for this gene in proper placental development and function.-Novakovic, B., Evain-Brion, D., Murthi, P., Fournier, T., Saffery, R. Variable DAXX gene methylation is a common feature of placental trophoblast differentiation, preeclampsia, and response to hypoxia.]]>
Wed, 22 Feb 2017 00:00:00 PST
Recent progress in diatom genomics and epigenomics. Tirichine L, Rastogi A, Bowler C
Curr Opin Plant Biol (Feb 2017)

Diatoms are one of the most diverse and successful groups of phytoplankton at the base of the food chain, sustaining life in the ocean and performing vital biogeochemical functions. The last fifteen years have witnessed the comprehensive analysis of several diatom genomes, revealing that they bear traces of their endosymbiotic origins from algal and heterotrophic ancestors, as well as significant gene transfer from bacteria. Their chimeric genomes are further regulated by a range of chromatin-based processes that are characteristic of both plant and animal genomes. We discuss the conservation of gene regulatory mechanisms in diatoms and propose that epigenetic processes may have a significant role in mediating responses to a highly dynamic and unpredictable environment in these organisms.]]>
Wed, 22 Feb 2017 00:00:00 PST
Plant Stress Responses and Phenotypic Plasticity in the Epigenomics Era: Perspectives on the Grapevine Scenario, a Model for Perennial Crop Plants. Fortes AM, Gallusci P
Front Plant Sci (2017)

Epigenetic marks include Histone Post-Translational Modifications and DNA methylation which are known to participate in the programming of gene expression in plants and animals. These epigenetic marks may be subjected to dynamic changes in response to endogenous and/or external stimuli and can have an impact on phenotypic plasticity. Studying how plant genomes can be epigenetically shaped under stressed conditions has become an essential issue in order to better understand the molecular mechanisms underlying plant stress responses and enabling epigenetic in addition to genetic factors to be considered when breeding crop plants. In this perspective, we discuss the contribution of epigenetic mechanisms to our understanding of plant responses to biotic and abiotic stresses. This regulation of gene expression in response to environment raises important biological questions for perennial species such as grapevine which is asexually propagated and grown worldwide in contrasting terroirs and environmental conditions. However, most species used for epigenomic studies are annual herbaceous plants, and epigenome dynamics has been poorly investigated in perennial woody plants, including grapevine. In this context, we propose grape as an essential model for epigenetic and epigenomic studies in perennial woody plants of agricultural importance.]]>
Tue, 21 Feb 2017 00:00:00 PST
Environmental epigenomics: Current approaches to assess epigenetic effects of endocrine disrupting compounds (EDC's) on human health. Tapia-Orozco N, Santiago-Toledo G, Barrón V, Espinosa-García AM, García-García JA, García-Arrazola R
Environ Toxicol Pharmacol (Feb 2017)

Environmental Epigenomics is a developing field to study the epigenetic effect on human health from exposure to environmental factors. Endocrine disrupting chemicals have been detected primarily in pharmaceutical drugs, personal care products, food additives, and food containers. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with a high incidence and prevalence of many endocrine-related disorders in humans. Nevertheless, further evidence is needed to establish a correlation between exposure to EDC and human disorders. Conventional detection of EDCs is based on chemical structure and concentration sample analysis. However, substantial evidence has emerged, suggesting that cell exposure to EDCs leads to epigenetic changes, independently of its chemical structure with non-monotonic low-dose responses. Consequently, a paradigm shift in toxicology assessment of EDCs is proposed based on a comprehensive review of analytical techniques used to evaluate the epigenetic effects. Fundamental insights reported elsewhere are compared in order to establish DNA methylation analysis as a viable method for assessing endocrine disruptors beyond the conventional study approach of chemical structure and concentration analysis.]]>
Mon, 20 Feb 2017 00:00:00 PST
[Clinical significance of hypermethylation of DLC-1 gene in myelodysplastic syndrome patients and effects of decitabine on DLC-1 gene expression]. Fu HY, Zhou HR, Yan JG, Chen CJ, Shen JZ
Zhonghua Yi Xue Za Zhi (Feb 2017)

Objective: To detect the methylation status of DLC-1 gene in the patients with myelodysplastic syndrome(MDS), the effect of abnormal methylation of DLC-1 gene on the expression of DLC-1 gene, the clinical significance of methylation of DLC-1 gene in MDS patients, and the effect of decitabine on DLC-1 gene expression. Methods: A total of 43 MDS patients were treated in Fujian Medical University Union Hospital from 2013 to 2015. Methylation status of DLC-1 gene in MDS patients were detected by the methylation specific PCR(MSP). The expression of DLC-1 gene mRNA was determined with real-time fluorescence quantitative PCR(RTFQ-PCR). MDS patients were divided into 5 groups (very low-risk, low-risk, intermediate-risk, high-risk and very high-risk, n=0, 8, 7, 18, 10) according to WPSS classification. And the clinical significance of methylation of DLC-1 gene in patients with MDS were investigated. In order to investigate the change in gene methylation and expression of DLC-1 gene after treatment with decitabine, methylation statuses of DLC-1 gene in MDS patients before and after be treated with decitabine were detected by the bisulfite sequencing PCR(BSP). The expressions of DLC-1 gene mRNA of these patients were determined with RTFQ-PCR. Results: Hypermethylation of CpG island of DLC-1 gene was observed in 55.16%(22/43)MDS patients. The expressions of DLC-1 gene mRNA in methylation positive patients were significantly lower than that in methylation negative patients (0.32±0.06 vs 0.91±0.11)(P=0.008). For MDS patients, the DLC-1 methylation rate of intermediate-and high-risk patient was 21/35, which was significantly higher than that of low-risk patient(1/8, P=0.006). The methylation status of DLC-1 gene were monitored in 8 patients before and after treatment with the decitabine (decitabine 20 mg/m(2,) d1-d5/d28, more than 4 courses) , the methylation rate of DLC-1 gene dropped from 57.50%±5.11% to 14.13%±2.07% after treatment(P=0.010). The expression of DLC-1 gene increased after treatment with decitabine(0.67±0.08 vs 0.28±0.06, P=0.015). Conclusions: Methylation of DLC-1 gene is common in MDS patients and may be associated with poor prognosis. Decitabine may activate the expression of DLC-1 gene by demethylation, which may be one of the mechanisms for the treatment of patients with MDS.]]>
Mon, 20 Feb 2017 00:00:00 PST
Childhood cancers and systems medicine. Stone WL, Klopfenstein KJ, Hajianpour MJ, Popescu MI, Cook CM, Krishnan K
Front Biosci (Landmark Ed) (Mar 2017)

Despite major advances in treatment, pediatric cancers in the 5-16 age group remain the most common cause of disease death, and one out of eight children with cancer will not survive. Among children that do survive, some 60% suffer from late effects such as cancer recurrence and increased risk of obesity. This paper will provide a broad overview of pediatric oncology in the context of systems medicine. Systems medicine utilizes an integrative approach that relies on patient information gained from omics technology. A major goal of a systems medicine is to provide personalized medicine that optimizes positive outcomes while minimizing deleterious short and long-term side-effects. There is an ever increasing development of effective cancer drugs, but a major challenge lies in picking the most effective drug for a particular patient. As detailed below, high-throughput omics technology holds the promise of solving this problem. Omics includes genomics, epigenomics, and proteomics. System medicine integrates omics information and provides detailed insights into disease mechanisms which can then inform the optimal treatment strategy.]]>
Wed, 15 Feb 2017 00:00:00 PST
A comparison of reference-based algorithms for correcting cell-type heterogeneity in Epigenome-Wide Association Studies. Teschendorff AE, Breeze CE, Zheng SC, Beck S
BMC Bioinformatics (Feb 2017)

Intra-sample cellular heterogeneity presents numerous challenges to the identification of biomarkers in large Epigenome-Wide Association Studies (EWAS). While a number of reference-based deconvolution algorithms have emerged, their potential remains underexplored and a comparative evaluation of these algorithms beyond tissues such as blood is still lacking.]]>
Tue, 14 Feb 2017 00:00:00 PST
Detection of Imprinted Genes by Single-Cell Allele-Specific Gene Expression. Santoni FA, Stamoulis G, Garieri M, Falconnet E, Ribaux P, Borel C, Antonarakis SE
Am J Hum Genet (Feb 2017)

Genomic imprinting results in parental-specific gene expression. Imprinted genes are involved in the etiology of rare syndromes and have been associated with common diseases such as diabetes and cancer. Standard RNA bulk cell sequencing applied to whole-tissue samples has been used to detect imprinted genes in human and mouse models. However, lowly expressed genes cannot be detected by using RNA bulk approaches. Here, we report an original and robust method that combines single-cell RNA-seq and whole-genome sequencing into an optimized statistical framework to analyze genomic imprinting in specific cell types and in different individuals. Using samples from the probands of 2 family trios and 3 unrelated individuals, 1,084 individual primary fibroblasts were RNA sequenced and more than 700,000 informative heterozygous single-nucleotide variations (SNVs) were genotyped. The allele-specific coverage per gene of each SNV in each single cell was used to fit a beta-binomial distribution to model the likelihood of a gene being expressed from one and the same allele. Genes presenting a significant aggregate allelic ratio (between 0.9 and 1) were retained to identify of the allelic parent of origin. Our approach allowed us to validate the imprinting status of all of the known imprinted genes expressed in fibroblasts and the discovery of nine putative imprinted genes, thereby demonstrating the advantages of single-cell over bulk RNA-seq to identify imprinted genes. The proposed single-cell methodology is a powerful tool for establishing a cell type-specific map of genomic imprinting.]]>
Mon, 13 Feb 2017 00:00:00 PST
Involvement of histone methylation in macrophage apoptosis and unstable plaque formation in methionine-induced hyperhomocysteinemic ApoE(-/-) mice. Cong G, Yan R, Huang H, Wang K, Yan N, Jin P, Zhang N, Hou J, Chen D, Jia S
Life Sci (Feb 2017)

Hyperhomocysteinemia (Hhcy) is an independent risk factor of atherosclerosis and promotes unstable plaque formation. Epigenetic mechanisms play an important role in the pathogenesis of atherosclerosis induced by Hhcy. However, the exact mechanism is still undefined. Lesional apoptotic cells and necrotic core formation contribute greatly to the progression of plaque. The present study sought to determine whether modification of histone methylation is involved in macrophage apoptosis and unstable plaque formation in the condition of Hhcy.]]>
Sat, 11 Feb 2017 00:00:00 PST
An Update on Molecular Diagnostic Testing of Human Imprinting Disorders. Grafodatskaya D, Choufani S, Basran R, Weksberg R
J Pediatr Genet (Mar 2017)

Imprinted genes are expressed in a parent of origin manner. Dysregulation of imprinted genes expression causes various disorders associated with abnormalities of growth, neurodevelopment, and metabolism. Molecular mechanisms leading to imprinting disorders and strategies for their diagnosis are discussed in this review article.]]>
Thu, 09 Feb 2017 00:00:00 PST
Dad's Snoring May Have Left Molecular Scars in Your DNA: the Emerging Role of Epigenetics in Sleep Disorders. Morales-Lara D, De-la-Peña C, Murillo-Rodríguez E
Mol Neurobiol (Feb 2017)

The sleep-wake cycle is a biological phenomena under the orchestration of neurophysiological, neurochemical, neuroanatomical, and genetical mechanisms. Moreover, homeostatic and circadian processes participate in the regulation of sleep across the light-dark period. Further complexity of the understanding of the genesis of sleep engages disturbances which have been characterized and classified in a variety of sleep-wake cycle disorders. The most prominent sleep alterations include insomnia as well as excessive daytime sleepiness. On the other side, several human diseases have been linked with direct changes in DNA, such as chromatin configuration, genomic imprinting, DNA methylation, histone modifications (acetylation, methylation, ubiquitylation or sumoylation, etc.), and activating RNA molecules that are transcribed from DNA but not translated into proteins. Epigenetic theories primarily emphasize the interaction between the environment and gene expression. According to these approaches, the environment to which mammals are exposed has a significant role in determining the epigenetic modifications occurring in chromosomes that ultimately would influence not only development but also the descendants' physiology and behavior. Thus, what makes epigenetics intriguing is that, unlike genetic variation, modifications in DNA are altered directly by the environment and, in some cases, these epigenetic changes may be inherited by future generations. Thus, it is likely that epigenetic phenomena might contribute to the homeostatic and/or circadian control of sleep and, possibly, have an undescribed link with sleep disorders. An exciting new horizon of research is arising between sleep and epigenetics since it represents the relevance of the study of how the genome learns from its experiences and modulates behavior, including sleep.]]>
Fri, 03 Feb 2017 00:00:00 PST
Genetic disorders: Steps towards epigenetic therapy for PWS. Crunkhorn S
Nat Rev Drug Discov (Feb 2017)

Thu, 02 Feb 2017 00:00:00 PST
Primer in Genetics and Genomics, Article 2-Advancing Nursing Research With Genomic Approaches. Lee H, Gill J, Barr T, Yun S, Kim H
Biol Res Nurs (Mar 2017)

Nurses investigate reasons for variable patient symptoms and responses to treatments to inform how best to improve outcomes. Genomics has the potential to guide nursing research exploring contributions to individual variability. This article is meant to serve as an introduction to the novel methods available through genomics for addressing this critical issue and includes a review of methodological considerations for selected genomic approaches.]]>
Tue, 31 Jan 2017 00:00:00 PST
DNA methylation of imprinted loci of autosomal chromosomes and IGF2 is not affected in Parkinson's disease patients' peripheral blood mononuclear cells. Kaut O, Sharma A, Schmitt I, Wüllner U
Neurol Res (Mar 2017)

 Genomic imprinting is an epigenetic phenomenon that results in differential expression of alleles, depending on their parental origin. The functional significance of DNA methylation in genomic imprinting has been widely investigated, and to date, approximately 100 imprinted genes have been identified in humans.]]>
Fri, 13 Jan 2017 00:00:00 PST
Association between DNA methyltransferase gene polymorphism and Parkinson's disease. Pezzi JC, de Bem CM, da Rocha TJ, Schumacher-Schuh AF, Chaves ML, Rieder CR, Hutz MH, Fiegenbaum M, Camozzato AL
Neurosci Lett (Feb 2017)

Parkinson's disease (PD) is a common and complex neurodegenerative disorder, the second most prevalent, only behind Alzheimer's disease. Recent studies suggest that environmental factors may contribute for neurodegeneration through induction of epigenetic modifications, such as DNA methylation, that is carried out by enzymes, such as DNMT1 and DNMT3B. This present study targeted to investigate the association among DNMT1 and DNMT3B polymorphisms with PD. Five hundred and twenty-two participants (214 PD patients following UK Brain Bank criteria and 308 healthy individuals) were evaluated. DNA was obtained from whole blood and genotypes were detected by an allelic discrimination assay using TaqMan(®) MGB probes on a real-time PCR system. The polymorphisms studied were rs2162560 and rs759920 (DNMT1) and rs2424913, rs998382 and rs2424932 (DNMT3B). Was found association between DNMT3B rs2424913 in T allele carriers with PD. The presence of the T allele was associated with PD (OR=1.80, 95% CI 1.16-2.81, p=0.009). No significant difference was observed for others DNMT3B SNPs. Also, no association between PD and the control group were observed for DNMT1 polymorphisms. This is the first study addressing an association between DNMT3B polymorphism and PD. The polymorphism may play a role in the pathogenesis of PD.]]>
Mon, 02 Jan 2017 00:00:00 PST
Calcifying nested stromal-epithelial tumor (CNSET) of the liver in Beckwith-Wiedemann syndrome. Khoshnam N, Robinson H, Clay MR, Schaffer LR, Gillespie SE, Shehata BM
Eur J Med Genet (Feb 2017)

Calcifying nested stromal-epithelial tumor (CNSET) is a rare neoplasm. In the 31 reported cases, CNSET is predominantly found in young girls and women. Beckwith-Wiedemann syndrome (BWS) (OMIM #130650) is an overgrowth syndrome with an increased risk to develop cancer. Associations have been seen between BWS and embryonal tumors, especially Wilms tumor, hepatoblastoma, and adrenocortical carcinoma. Here we report on a female patient with BWS who presented with CNSET. Two other cases with the same association have been reported, with our case representing the third such reported in the literature. Although we recognize a potential reporting bias we speculate that CNSET may represent an unrecognized addition to the spectrum of BWS tumorigenesis.]]>
Wed, 14 Dec 2016 00:00:00 PST
Deletion of conserved sequences in IG-DMR at Dlk1-Gtl2 locus suggests their involvement in expression of paternally expressed genes in mice. Saito T, Hara S, Tamano M, Asahara H, Takada S
J Reprod Dev (Feb 2017)

Expression regulation of the Dlk1-Dio3 imprinted domain by the intergenic differentially methylated region (IG-DMR) is essential for normal embryonic development in mammals. In this study, we investigated conserved IG-DMR genomic sequences in eutherians to elucidate their role in genomic imprinting of the Dlk1-Dio3 domain. Using a comparative genomics approach, we identified three highly conserved sequences in IG-DMR. To elucidate the functions of these sequences in vivo, we generated mutant mice lacking each of the identified highly conserved sequences using the CRISPR/Cas9 system. Although mutant mice did not exhibit the gross phenotype, deletions of the conserved sequences altered the expression levels of paternally expressed imprinted genes in the mutant embryos without skewing imprinting status. These results suggest that the conserved sequences in IG-DMR are involved in the expression regulation of some of the imprinted genes in the Dlk1-Dio3 domain.]]>
Thu, 01 Dec 2016 00:00:00 PST
Epigenetics of cell fate reprogramming and its implications for neurological disorders modelling. Grzybek M, Golonko A, Walczak M, Lisowski P
Neurobiol Dis (Mar 2017)

The reprogramming of human induced pluripotent stem cells (hiPSCs) proceeds in a stepwise manner with reprogramming factors binding and epigenetic composition changes during transition to maintain the epigenetic landscape, important for pluripotency. There arises a question as to whether the aberrant epigenetic state after reprogramming leads to epigenetic defects in induced stem cells causing unpredictable long term effects in differentiated cells. In this review, we present a comprehensive view of epigenetic alterations accompanying reprogramming, cell maintenance and differentiation as factors that influence applications of hiPSCs in stem cell based technologies. We conclude that sample heterogeneity masks DNA methylation signatures in subpopulations of cells and thus believe that beside a genetic evaluation, extensive epigenomic screening should become a standard procedure to ensure hiPSCs state before they are used for genome editing and differentiation into neurons of interest. In particular, we suggest that exploitation of the single-cell composition of the epigenome will provide important insights into heterogeneity within hiPSCs subpopulations to fast forward development of reliable hiPSC-based analytical platforms in neurological disorders modelling and before completed hiPSC technology will be implemented in clinical approaches.]]>
Mon, 28 Nov 2016 00:00:00 PST
Strigolactone biology: genes, functional genomics, epigenetics and applications. Makhzoum A, Yousefzadi M, Malik S, Gantet P, Tremouillaux-Guiller J
Crit Rev Biotechnol (Mar 2017)

Strigolactones (SLs) represent an important new plant hormone class marked by their multifunctional role in plant and rhizosphere interactions. These compounds stimulate hyphal branching in arbuscular mycorrhizal fungi (AMF) and seed germination of root parasitic plants. In addition, they are involved in the control of plant architecture by inhibiting bud outgrowth as well as many other morphological and developmental processes together with other plant hormones such as auxins and cytokinins. The biosynthetic pathway of SLs that are derived from carotenoids was partially decrypted based on the identification of mutants from a variety of plant species. Only a few SL biosynthetic and regulated genes and related regulatory transcription factors have been identified. However, functional genomics and epigenetic studies started to give first elements on the modality of the regulation of SLs related genes. Since they control plant architecture and plant-rhizosphere interaction, SLs start to be used for agronomical and biotechnological applications. Furthermore, the genes involved in the SL biosynthetic pathway and genes regulated by SL constitute interesting targets for plant breeding. Therefore, it is necessary to decipher and better understand the genetic determinants of their regulation at different levels.]]>
Wed, 16 Dec 2015 00:00:00 PST