'; ?> 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 Sun, 26 Mar 2017 07:03:18 PDT Sun, 26 Mar 2017 07:03:18 PDT jirtle@radonc.duke.edu james001@jirtle.com DNA methylation imprinting errors in spermatogenic cells from maturation arrest azoospermic patients. Marques PI, Fernandes S, Carvalho F, Barros A, Sousa M, Marques CJ
Andrology (Mar 2017)

Imprinting errors have been described in spermatozoa from infertile patients with oligozoospermia and azoospermia. However, little is known about methylation of imprinted genes in other spermatogenic cells from azoospermic patients. Therefore, we aimed to evaluate the methylation status of single CpGs located in the differentially methylated regions (DMRs) of two imprinted genes, one paternally (H19) and one maternally (MEST) methylated, in primary spermatocytes of azoospermic patients presenting complete (MAc, n = 7) and incomplete (MAi, n = 8) maturation arrest, as well as in other spermatogenic cells from MAi patients that presented focus of complete spermatogenesis in some seminiferous tubules. We observed H19 imprinting errors in primary spermatocytes from one MAi patient and MEST imprinting errors in one MAi and two MAc patients. Additionally, H19 imprinting errors were observed in elongated spermatids/spermatozoa from one MAi patient. Nevertheless, no statistical differences were found for H19 and MEST global methylation levels (percentage of methylated and unmethylated CpGs, respectively) between patients with complete and incomplete MA and also between MA groups and a control group. These results provide further evidence that imprinting errors occur in spermatogenic cells from patients presenting impaired spermatogenesis, as we and others have previously described in ejaculated and testicular spermatozoa. As paternal imprinting errors can be transmitted to the embryo by the sperm cell, they can provide a possible explanation for poor embryo development and/or low pregnancy rates as correct expression of imprinted genes is crucial for embryo and placental development and function. Therefore, in cases with male factor infertility where unsuccessful in vitro fertilization (IVF) treatments are recurrent, analysis of imprinting marks in spermatozoa might be a useful diagnostic tool.]]>
Wed, 15 Mar 2017 00:00:00 PDT
Molecular mechanisms and therapeutic targets in pediatric brain tumors. Liu KW, Pajtler KW, Worst BC, Pfister SM, Wechsler-Reya RJ
Sci Signal (Mar 2017)

Brain tumors are among the leading causes of cancer-related deaths in children. Although surgery, aggressive radiation, and chemotherapy have improved outcomes, many patients still die of their disease. Moreover, those who survive often suffer devastating long-term side effects from the therapies. A greater understanding of the molecular underpinnings of these diseases will drive the development of new therapeutic approaches. Advances in genomics and epigenomics have provided unprecedented insight into the molecular diversity of these diseases and, in several cases, have revealed key genes and signaling pathways that drive tumor growth. These not only serve as potential therapeutic targets but also have facilitated the creation of animal models that faithfully recapitulate the human disease for preclinical studies. In this Review, we discuss recent progress in understanding the molecular basis of the three most common malignant pediatric brain tumors-medulloblastoma, ependymoma, and high-grade glioma-and the implications for development of safer and more effective therapies.]]>
Wed, 15 Mar 2017 00:00:00 PDT
Paternal Genome Elimination in Liposcelis Booklice (Insecta: Psocodea). Hodson CN, Hamilton PT, Dilworth D, Nelson CJ, Curtis CI, Perlman SJ
Genetics (Mar 2017)

How sex is determined in insects is diverse and dynamic, and includes male heterogamety, female heterogamety, and haplodiploidy. In many insect lineages, sex determination is either completely unknown or poorly studied. We studied sex determination in Psocodea, a species-rich order of insects that includes parasitic lice, barklice, and booklice. We focus on a recently discovered species of Liposcelis booklice (Troctomorpha: Psocodea), which are among the closest free-living relatives of parasitic lice. Using genetic, genomic, and immunohistochemical approaches, we show that this group exhibits paternal genome elimination (PGE), an unusual mode of sex determination that involves genomic imprinting. Controlled crosses, following a genetic marker over multiple generations, demonstrated that males only transmit genes they inherited from their mother to offspring. Immunofluorescence microscopy revealed densely packed chromocenters associated with H3K9me3, a conserved marker for heterochromatin, in males, but not in females, suggesting silencing of chromosomes in males. Genome assembly and comparison of read coverage in male and female libraries showed no evidence for differentiated sex chromosomes. We also found that females produce more sons early in life, consistent with facultative sex allocation. It is likely that PGE is widespread in Psocodea, including human lice. This order represents a promising model for studying this enigmatic mode of sex determination.]]>
Wed, 15 Mar 2017 00:00:00 PDT
Role of DNA methylation in imprinting disorders: an updated review. Elhamamsy AR
J Assist Reprod Genet (Mar 2017)

Genomic imprinting is a complex epigenetic process that contributes substantially to embryogenesis, reproduction, and gametogenesis. Only small fraction of genes within the whole genome undergoes imprinting. Imprinted genes are expressed in a monoallelic parent-of-origin-specific manner, which means that only one of the two inherited alleles is expressed either from the paternal or maternal side. Imprinted genes are typically arranged in clusters controlled by differentially methylated regions or imprinting control regions. Any defect or relaxation in imprinting process can cause loss of imprinting in the key imprinted loci. Loss of imprinting in most cases has a harmful effect on fetal development and can result in neurological, developmental, and metabolic disorders. Since DNA methylation and histone modifications play a key role in the process of imprinting. This review focuses on the role of DNA methylation in imprinting process and describes DNA methylation aberrations in different imprinting disorders.]]>
Fri, 10 Mar 2017 00:00:00 PST
Exploring the epigenetic drug discovery landscape. Prachayasittikul V, Prathipati P, Pratiwi R, Phanus-Umporn C, Malik AA, Schaduangrat N, Seenprachawong K, Wongchitrat P, Supokawej A, Prachayasittikul V, Wikberg JE, Nantasenamat C
Expert Opin Drug Discov (Apr 2017)

Epigenetic modification has been implicated in a wide range of diseases and the ability to modulate such systems is a lucrative therapeutic strategy in drug discovery. Areas covered: This article focuses on the concepts and drug discovery aspects of epigenomics. This is achieved by providing a survey of the following concepts: (i) factors influencing epigenetics, (ii) diseases arising from epigenetics, (iii) epigenetic enzymes as druggable targets along with coverage of existing FDA-approved drugs and pharmacological agents, and (iv) drug repurposing/repositioning as a means for rapid discovery of pharmacological agents targeting epigenetics. Expert opinion: Despite significant interests in targeting epigenetic modifiers as a therapeutic route, certain classes of target proteins are heavily studied while some are less characterized. Thus, such orphan target proteins are not yet druggable with limited report of active modulators. Current research points towards a great future with novel drugs directed to the many complex multifactorial diseases of humans, which are still often poorly understood and difficult to treat.]]>
Thu, 09 Mar 2017 00:00:00 PST
DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility. Ambatipudi S, Horvath S, Perrier F, Cuenin C, Hernandez-Vargas H, Le Calvez-Kelm F, Durand G, Byrnes G, Ferrari P, Bouaoun L, Sklias A, Chajes V, Overvad K, Severi G, Baglietto L, Clavel-Chapelon F, Kaaks R, Barrdahl M, Boeing H, Trichopoulou A, Lagiou P, Naska A, Masala G, Agnoli C, Polidoro S, Tumino R, Panico S, Dollé M, Peeters PH, Onland-Moret NC, Sandanger TM, Nøst TH, Weiderpass E, Quirós JR, Agudo A, Rodriguez-Barranco M, Huerta Castaño JM, Barricarte A, Fernández AM, Travis RC, Vineis P, Muller DC, Riboli E, Gunter M, Romieu I, Herceg Z
Eur J Cancer (Apr 2017)

A vast majority of human malignancies are associated with ageing, and age is a strong predictor of cancer risk. Recently, DNA methylation-based marker of ageing, known as 'epigenetic clock', has been linked with cancer risk factors. This study aimed to evaluate whether the epigenetic clock is associated with breast cancer risk susceptibility and to identify potential epigenetics-based biomarkers for risk stratification.]]>
Sat, 04 Mar 2017 00:00:00 PST
Epigenetics and Health Disparities. Vick AD, Burris HH
Curr Epidemiol Rep (Mar 2017)

African Americans disproportionately suffer from leading causes of morbidity and mortality including cardiovascular disease (CVD), cancer, and preterm birth. Disparities can arise from multiple social and environmental exposures, but how the human body responds to these exposures to result in pathophysiologic states is incompletely understood.]]>
Fri, 03 Mar 2017 00:00:00 PST
Diverse Non-genetic, Allele-Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain. Huang WC, Ferris E, Cheng T, Hörndli CS, Gleason K, Tamminga C, Wagner JD, Boucher KM, Christian JL, Gregg C
Neuron (Mar 2017)

Interactions between genetic and epigenetic effects shape brain function, behavior, and the risk for mental illness. Random X inactivation and genomic imprinting are epigenetic allelic effects that are well known to influence genetic architecture and disease risk. Less is known about the nature, prevalence, and conservation of other potential epigenetic allelic effects in vivo in the mouse and primate brain. Here we devise genomics, in situ hybridization, and mouse genetics strategies to uncover diverse allelic effects in the brain that are not caused by imprinting or genetic variation. We found allelic effects that are developmental stage and cell type specific, that are prevalent in the neonatal brain, and that cause mosaics of monoallelic brain cells that differentially express wild-type and mutant alleles for heterozygous mutations. Finally, we show that diverse non-genetic allelic effects that impact mental illness risk genes exist in the macaque and human brain. Our findings have potential implications for mammalian brain genetics. VIDEO ABSTRACT.]]>
Mon, 27 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
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 (Mar 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 (Mar 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
Dissecting genomic imprinting and genetic conflict from a game theory prospective: Comment on: "Epigenetic game theory: How to compute the epigenetic control of maternal-to-zygotic transition" by Qian Wang et al. Cui Y, Yang H
Phys Life Rev (Mar 2017)

Sat, 04 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
Profiling of human epigenetic regulators using a semi-automated real-time qPCR platform validated by next generation sequencing. Dudakovic A, Gluscevic M, Paradise CR, Dudakovic H, Khani F, Thaler R, Ahmed FS, Li X, Dietz AB, Stein GS, Montecino MA, Deyle DR, Westendorf JJ, van Wijnen AJ
Gene (Apr 2017)

Epigenetic mechanisms control phenotypic commitment of mesenchymal stromal/stem cells (MSCs) into osteogenic, chondrogenic or adipogenic lineages. To investigate enzymes and chromatin binding proteins controlling the epigenome, we developed a hybrid expression screening strategy that combines semi-automated real-time qPCR (RT-qPCR), next generation RNA sequencing (RNA-seq), and a novel data management application (FileMerge). This strategy was used to interrogate expression of a large cohort (n>300) of human epigenetic regulators (EpiRegs) that generate, interpret and/or edit the histone code. We find that EpiRegs with similar enzymatic functions are variably expressed and specific isoforms dominate over others in human MSCs. This principle is exemplified by analysis of key histone acetyl transferases (HATs) and deacetylases (HDACs), H3 lysine methyltransferases (e.g., EHMTs) and demethylases (KDMs), as well as bromodomain (BRDs) and chromobox (CBX) proteins. Our results show gender-specific expression of H3 lysine 9 [H3K9] demethylases (e.g., KDM5D and UTY) as expected and upregulation of distinct EpiRegs (n>30) during osteogenic differentiation of MSCs (e.g., HDAC5 and HDAC7). The functional significance of HDACs in osteogenic lineage commitment of MSCs was functionally validated using panobinostat (LBH-589). This pan-deacetylase inhibitor suppresses osteoblastic differentiation as evidenced by reductions in bone-specific mRNA markers (e.g., ALPL), alkaline phosphatase activity and calcium deposition (i.e., Alizarin Red staining). Thus, our RT-qPCR platform identifies candidate EpiRegs by expression screening, predicts biological outcomes of their corresponding inhibitors, and enables manipulation of the human epigenome using molecular or pharmacological approaches to control stem cell differentiation.]]>
Mon, 30 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
Epigenetics of psoriatic disease: A systematic review and critical appraisal. Pollock RA, Abji F, Gladman DD
J Autoimmun (Mar 2017)

Psoriasis is an inflammatory disease of the skin that is sometimes accompanied by an auto-inflammatory arthritis called psoriatic arthritis (PsA). Psoriasis and PsA are multifactorial diseases that result from complex interactions of environmental and genetic risk factors. Epigenetic marks, which are labile chemical marks with diverse functions, form a layer of biological information that sits at the interface of genetics and the environment. Aberrant epigenetic regulation has been previously implicated in other rheumatological disorders. The purpose of this review is to summarize and critically evaluate the nascent literature on epigenetics in psoriasis and PsA. A systematic review yielded 52 primary articles after applying inclusion and exclusion criteria. Data were extracted using a standardized template and study quality assessed using a methodological quality checklist. Studies reflect a broad range of epigenetic sub-disciplines, the most common being DNA methylation, followed by the parent of origin effect or genomic imprinting, expression or activity of epigenetic modifying enzymes, and histone modifications. Epidemiological studies demonstrating excessive paternal transmission provided the earliest evidence of epigenetic deregulation in psoriatic disease, however few studies have examined its molecular mechanisms. Methylation studies evolved rapidly from low resolution global to targeted analyses of known psoriatic disease susceptibility loci such as HLA-C*0602. The recent explosion of epigenome-wide association studies has provided us with novel insights into psoriasis pathogenesis, and the mechanism of action of UVB, methotrexate, and anti-TNF therapies, as well as molecular signatures of psoriasis that may have clinical relevance. Finally, recent studies of pharmacological inhibitors of epigenetic modifier enzymes demonstrate their potential applicability as novel treatment modalities for psoriasis. Challenges of epigenetics research in psoriasis and PsA were identified and future perspectives are discussed herein.]]>
Wed, 14 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
Dynamic and Antagonistic Allele-Specific Epigenetic Modifications Controlling the Expression of Imprinted Genes in Maize Endosperm. Dong X, Zhang M, Chen J, Peng L, Zhang N, Wang X, Lai J
Mol Plant (Mar 2017)

Genomic imprinting is often associated with allele-specific epigenetic modifications. Although many reports suggested potential roles of DNA methylation and H3K27me3 in regulating genomic imprinting, the contributions of allele-specific active histone modifications to imprinting remain still unclear in plants. Here, we report the identification of 337 high-stringency allele-specific H3K4me3 and H3K36me3 peaks in maize endosperm. Paternally preferred H3K4me3 and H3K36me3 peaks mostly co-localized with paternally expressed genes (PEGs), while endosperm-specific maternally expressed genes (endo-MEGs) were associated with maternally preferred H3K4me3 and H3K36me3 peaks. A unique signature for PEGs was observed, where the active H3K4me4 and H3K36me3 as well as repressive H3K27me3 appeared together. At the gene body of con-PEGs (constitutively expressed PEG), H3K27me3 and H3K36me3 were specifically deposited on hypomethylated maternal alleles and hypermethylated paternal alleles, respectively. Around the transcription start sites of endo-MEGs, DNA methylation and H3K4me3 specifically marked paternal and maternal alleles, respectively. In addition, 35 maternally expressed non-coding RNAs exhibited the same allele-specific epigenetic features as endo-MEGs, indicating similar mechanisms for the regulation of imprinted genes and non-coding RNAs. Taken together, our results uncover the complex patterns of mutually exclusive epigenetic modifications deposited at different alleles of imprinted genes that are required for genomic imprinting in maize endosperm.]]>
Sat, 29 Oct 2016 00:00:00 PDT
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