'; ?> 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, 28 Jul 2016 10:32:29 PDT Thu, 28 Jul 2016 10:32:29 PDT jirtle@radonc.duke.edu james001@jirtle.com Epigenetics ELSI: Darker Than You Think? Joly Y, So D, Saulnier K, Dyke SO
Trends Genet (Jul 2016)

Emerging ethical, legal, and social implications (ELSI) scholarship in epigenetics has focused largely on hypothetical issues involving institutional racism, discrimination, and eugenics. To avoid an unwarranted backlash against this promising research field, we encourage a more balanced ELSI discussion conveying the full spectrum of issues faced by stakeholders.]]>
Wed, 27 Jul 2016 00:00:00 PDT
ATP-binding cassette transmembrane transporters and their epigenetic control in cancer: an overview. Arrigoni E, Galimberti S, Petrini M, Danesi R, Di Paolo A
Expert Opin Drug Metab Toxicol (Jul 2016)

Members of the ATP-binding cassette (ABC) transmembrane transporters control the passage of several substrates across cell membranes, including drugs. This means that ABC transporters may exert a significant influence on the kinetics and dynamics of pharmacological agents, being responsible for the occurrence of multidrug-resistant (MDR) phenotype. Pharmacogenetic analyses have shed light on gene expression and polymorphisms as possible markers predictive of transporter activity. However, a non-negligible part of the variability in drug pharmacokinetics and pharmacodynamics still remains. Further research has demonstrated that different epigenetic mechanisms exert a coordinated control over ABC genes, and on the corresponding MDR phenotype.]]>
Tue, 26 Jul 2016 00:00:00 PDT
Complete in vitro generation of fertile oocytes from mouse primordial germ cells. Morohaku K, Tanimoto R, Sasaki K, Kawahara-Miki R, Kono T, Hayashi K, Hirao Y, Obata Y
Proc Natl Acad Sci U S A (Jul 2016)

Reconstituting gametogenesis in vitro is a key goal for reproductive biology and regenerative medicine. Successful in vitro reconstitution of primordial germ cells and spermatogenesis has recently had a significant effect in the field. However, recapitulation of oogenesis in vitro remains unachieved. Here we demonstrate the first reconstitution, to our knowledge, of the entire process of mammalian oogenesis in vitro from primordial germ cells, using an estrogen-receptor antagonist that promotes normal follicle formation, which in turn is crucial for supporting oocyte growth. The fundamental events in oogenesis (i.e., meiosis, oocyte growth, and genomic imprinting) were reproduced in the culture system. The most rigorous evidence of the recapitulation of oogenesis was the birth of fertile offspring, with a maximum of seven pups obtained from a cultured gonad. Moreover, cryopreserved gonads yielded functional oocytes and offspring in this culture system. Thus, our in vitro system will enable both innovative approaches for a deeper understanding of oogenesis and a new avenue to create and preserve female germ cells.]]>
Tue, 26 Jul 2016 00:00:00 PDT
New Perspectives on Genomic Imprinting, an Essential and Multifaceted Mode of Epigenetic Control in the Developing and Adult Brain. Perez JD, Rubinstein ND, Dulac C
Annu Rev Neurosci (Jul 2016)

Mammalian evolution entailed multiple innovations in gene regulation, including the emergence of genomic imprinting, an epigenetic regulation leading to the preferential expression of a gene from its maternal or paternal allele. Genomic imprinting is highly prevalent in the brain, yet, until recently, its central roles in neural processes have not been fully appreciated. Here, we provide a comprehensive survey of adult and developmental brain functions influenced by imprinted genes, from neural development and wiring to synaptic function and plasticity, energy balance, social behaviors, emotions, and cognition. We further review the widespread identification of parental biases alongside monoallelic expression in brain tissues, discuss their potential roles in dosage regulation of key neural pathways, and suggest possible mechanisms underlying the dynamic regulation of imprinting in the brain. This review should help provide a better understanding of the significance of genomic imprinting in the normal and pathological brain of mammals including humans.]]>
Fri, 22 Jul 2016 00:00:00 PDT
Toward high-resolution population genomics using archaeological samples. Morozova I, Flegontov P, Mikheyev AS, Bruskin S, Asgharian H, Ponomarenko P, Klyuchnikov V, ArunKumar G, Prokhortchouk E, Gankin Y, Rogaev E, Nikolsky Y, Baranova A, Elhaik E, Tatarinova TV
DNA Res (Jul 2016)

The term 'ancient DNA' (aDNA) is coming of age, with over 1,200 hits in the PubMed database, beginning in the early 1980s with the studies of 'molecular paleontology'. Rooted in cloning and limited sequencing of DNA from ancient remains during the pre-PCR era, the field has made incredible progress since the introduction of PCR and next-generation sequencing. Over the last decade, aDNA analysis ushered in a new era in genomics and became the method of choice for reconstructing the history of organisms, their biogeography, and migration routes, with applications in evolutionary biology, population genetics, archaeogenetics, paleo-epidemiology, and many other areas. This change was brought by development of new strategies for coping with the challenges in studying aDNA due to damage and fragmentation, scarce samples, significant historical gaps, and limited applicability of population genetics methods. In this review, we describe the state-of-the-art achievements in aDNA studies, with particular focus on human evolution and demographic history. We present the current experimental and theoretical procedures for handling and analysing highly degraded aDNA. We also review the challenges in the rapidly growing field of ancient epigenomics. Advancement of aDNA tools and methods signifies a new era in population genetics and evolutionary medicine research.]]>
Wed, 20 Jul 2016 00:00:00 PDT
The epigenomics of polycystic ovarian syndrome: from pathogenesis to clinical manifestations. Li S, Zhu D, Duan H, Tan Q
Gynecol Endocrinol (Jul 2016)

Polycystic ovarian syndrome (PCOS) is a complex condition of ovarian dysfunction and metabolic abnormalities with widely varying clinical manifestations resulting from interference of the genome and the environment through integrative biological mechanisms with the emerging field of epigenetics offering an appealing tool for studying the nature and nurture of the disease. We review the current literature of epigenetic studies on PCOS from disease development to the association analysis of the DNA methylome and to exploratory studies on the molecular mechanisms of disease heterogeneity and comorbidity. Recent data based on profiling of the DNA methylome of PCOS in different tissues provided consistent molecular evidence in support of epidemiological findings on disease comorbidity suggesting a possible autoimmune basis in the pathogenesis of the disease. We show that the field of epigenetics and epigenomics could serve to link molecular regulatory mechanisms with disease development and disease manifestation which could contribute to PCOS prevention and treatment and eventually promote reproductive health in fertile age women. We summarize the up-to-date findings and discuss the implications of various studies and point to new avenues of research on PCOS in the rapidly developing field of epigenetics and epigenomics.]]>
Mon, 18 Jul 2016 00:00:00 PDT
Meta-analysis of Telomere Length in Alzheimer's Disease. Forero DA, González-Giraldo Y, López-Quintero C, Castro-Vega LJ, Barreto GE, Perry G
J Gerontol A Biol Sci Med Sci (Aug 2016)

Alzheimer's disease (AD) is a common and severe neurodegenerative disorder. Human telomeres are fundamental for the maintenance of genomic stability and play prominent roles in both cellular senescence and organismal aging. Regulation of telomere length (TL) is the result of the complex interplay between environmental and genetic factors. Alterations in TL are increasingly being studied as a possible risk factor for AD, and published studies on TL in AD show discrepant results, highlighting the need for a meta-analysis.]]>
Sat, 16 Jul 2016 00:00:00 PDT
Mendelian randomization in (epi)genetic epidemiology: an effective tool to be handled with care. Latvala A, Ollikainen M
Genome Biol (2016)

A study examining blood lipid traits takes epigenomics approaches to the next level by using carefully performed Mendelian randomization to assess causality rather than simply reporting associations.See related research article: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1000-6.]]>
Fri, 15 Jul 2016 00:00:00 PDT
The Many Roles of BAF (mSWI/SNF) and PBAF Complexes in Cancer. Hodges C, Kirkland JG, Crabtree GR
Cold Spring Harb Perspect Med (Jul 2016)

During the last decade, a host of epigenetic mechanisms were found to contribute to cancer and other human diseases. Several genomic studies have revealed that ∼20% of malignancies have alterations of the subunits of polymorphic BRG-/BRM-associated factor (BAF) and Polybromo-associated BAF (PBAF) complexes, making them among the most frequently mutated complexes in cancer. Recurrent mutations arise in genes encoding several BAF/PBAF subunits, including ARID1A, ARID2, PBRM1, SMARCA4, and SMARCB1 These subunits share some degree of conservation with subunits from related adenosine triphosphate (ATP)-dependent chromatin remodeling complexes in model organisms, in which a large body of work provides insight into their roles in cancer. Here, we review the roles of BAF- and PBAF-like complexes in these organisms, and relate these findings to recent discoveries in cancer epigenomics. We review several roles of BAF and PBAF complexes in cancer, including transcriptional regulation, DNA repair, and regulation of chromatin architecture and topology. More recent results highlight the need for new techniques to study these complexes.]]>
Thu, 14 Jul 2016 00:00:00 PDT
Single-cell genome-wide studies give new insight into nongenetic cell-to-cell variability in animals. Golov AK, Razin SV, Gavrilov AA
Histochem Cell Biol (Jul 2016)

Huge numbers of cells form an adult animal body, ranging from several thousands in Placozoa and small nematodes to many billions in mammals. Cells are classified into separate groups known as cell types by their morphological and biochemical features. Six to several hundreds of spatially ordered cell types are recognized in different animals. This complex organization develops from one cell, a zygote, during ontogeny, and its dynamic equilibrium is often maintained in the adult body. One of the key challenges in biology is to understand the mechanisms that sustain the reproducible development of a complex ordered cell ensemble such as the animal body from a single cell. How cells with identical genomes stably maintain one of the numerous possible phenotypes? How the cell differentiation lineage is selected during development? What genes play a key role in maintaining cell identity, and how do they determine expression of other genes characteristic of the relevant cell type? How does the basically stochastic nature of transcription in an isolated cell affect the stability of cell identity, the selection of a cell lineage, and the variability of cell responses to external stimuli? Better-grounded answers to these questions have become possible with recent progress in single-cell genome-wide analysis techniques, which combine the high throughput of biochemical methods and the differential nature of microscopy. The techniques are still in their infancy, and their further development will certainly revolutionize many fields of life sciences and, in particular, developmental biology. Here, we summarize the main results that have been obtained in single-cell genome-wide analyses and describe the nongenetic cell-to-cell variability in animals.]]>
Thu, 14 Jul 2016 00:00:00 PDT
Joint Bayesian inference of risk variants and tissue-specific epigenomic enrichments across multiple complex human diseases. Li Y, Kellis M
Nucleic Acids Res (Jul 2016)

Genome wide association studies (GWAS) provide a powerful approach for uncovering disease-associated variants in human, but fine-mapping the causal variants remains a challenge. This is partly remedied by prioritization of disease-associated variants that overlap GWAS-enriched epigenomic annotations. Here, we introduce a new Bayesian model RiVIERA (Risk Variant Inference using Epigenomic Reference Annotations) for inference of driver variants from summary statistics across multiple traits using hundreds of epigenomic annotations. In simulation, RiVIERA promising power in detecting causal variants and causal annotations, the multi-trait joint inference further improved the detection power. We applied RiVIERA to model the existing GWAS summary statistics of 9 autoimmune diseases and Schizophrenia by jointly harnessing the potential causal enrichments among 848 tissue-specific epigenomics annotations from ENCODE/Roadmap consortium covering 127 cell/tissue types and 8 major epigenomic marks. RiVIERA identified meaningful tissue-specific enrichments for enhancer regions defined by H3K4me1 and H3K27ac for Blood T-Cell specifically in the nine autoimmune diseases and Brain-specific enhancer activities exclusively in Schizophrenia. Moreover, the variants from the 95% credible sets exhibited high conservation and enrichments for GTEx whole-blood eQTLs located within transcription-factor-binding-sites and DNA-hypersensitive-sites. Furthermore, joint modeling the nine immune traits by simultaneously inferring and exploiting the underlying epigenomic correlation between traits further improved the functional enrichments compared to single-trait models.]]>
Wed, 13 Jul 2016 00:00:00 PDT
A Comparative Analysis of 5-Azacytidine and Zebularine induced DNA Demethylation. Griffin PT, Niederhuth CE, Schmitz RJ
G3 (Bethesda) (Jul 2016)

The non-methylable cytosine analogs, 5-azacytidine and zebularine, are widely used to inhibit DNA methyltransferase activity and reduce genomic DNA methylation. In this study, whole-genome bisulfite sequencing is used to construct maps of DNA methylation with single base pair resolution in Arabidopsis thaliana seedlings treated with each demethylating agent. We find that both inhibitor treatments result in nearly indistinguishable patterns of genome-wide DNA methylation and that 5-azacytidine had a slightly greater demethylating effect at higher concentrations across the genome. Transcriptome analyses revealed a substantial number of up-regulated genes, with an overrepresentation of transposable element genes, in particular CACTA-like elements. This demonstrates that chemical demethylating agents have a disproportionately large effect on loci that are otherwise silenced by DNA methylation.]]>
Tue, 12 Jul 2016 00:00:00 PDT
Fine-scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer. Shi J, Zhang Y, Zheng W, Michailidou K, Ghoussaini M, Bolla MK, Wang Q, Dennis J, Lush M, Milne RL, Shu XO, Beesley J, Kar S, Andrulis IL, Anton-Culver H, Arndt V, Beckmann MW, Zhao Z, Guo X, Benitez J, Beeghly-Fadiel A, Blot W, Bogdanova NV, Bojesen SE, Brauch H, Brenner H, Brinton L, Broeks A, Brüning T, Burwinkel B, Cai H, Canisius S, Chang-Claude J, Choi JY, Couch FJ, Cox A, Cross SS, Czene K, Darabi H, Devilee P, Droit A, Dork T, Fasching PA, Fletcher O, Flyger H, Fostira F, Gaborieau V, García-Closas M, Giles GG, Grip M, Guenel P, Haiman CA, Hamann U, Hartman M, Miao H, Hollestelle A, Hopper JL, Hsiung CN,  , Ito H, Jakubowska A, Johnson N, Torres D, Kabisch M, Kang D, Khan S, Knight JA, Kosma VM, Lambrechts D, Li J, Lindblom A, Lophatananon A, Lubinski J, Mannermaa A, Manoukian S, Le Marchand L, Margolin S, Marme F, Matsuo K, McLean C, Meindl A, Muir K, Neuhausen SL, Nevanlinna H, Nord S, Børresen-Dale AL, Olson JE, Orr N, van den Ouweland AM, Peterlongo P, Choudary Putti T, Rudolph A, Sangrajrang S, Sawyer EJ, Schmidt MK, Schmutzler RK, Shen CY, Hou MF, Shrubsole MJ, Southey MC, Swerdlow A, Hwang Teo S, Thienpont B, Toland AE, Tollenaar RA, Tomlinson I, Truong T, Tseng CC, Wen W, Winqvist R, Wu AH, Har Yip C, Zamora PM, Zheng Y, Floris G, Cheng CY, Hooning MJ, Martens JW, Seynaeve C, Kristensen VN, Hall P, Pharoah PD, Simard J, Chenevix-Trench G, Dunning AM, Antoniou AC, Easton DF, Cai Q, Long J
Int J Cancer (Sep 2016)

Previous genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine-mapping study across 2.06 Mb (chr8:127,561,724-129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93-0.97, conditional p = 5.8 × 10(-6) ), rs7815245 (OR = 0.94, 95% CI = 0.91-0.96, conditional p = 1.1 × 10(-6) ) and rs2033101 (OR = 1.05, 95% CI = 1.02-1.07, conditional p = 1.1 × 10(-4) ) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r(2)  = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry.]]>
Sat, 09 Jul 2016 00:00:00 PDT
Integrating epigenomic data and 3D genomic structure with a new measure of chromatin assortativity. Pancaldi V, Carrillo-de-Santa-Pau E, Javierre BM, Juan D, Fraser P, Spivakov M, Valencia A, Rico D
Genome Biol (2016)

Network analysis is a powerful way of modeling chromatin interactions. Assortativity is a network property used in social sciences to identify factors affecting how people establish social ties. We propose a new approach, using chromatin assortativity, to integrate the epigenomic landscape of a specific cell type with its chromatin interaction network and thus investigate which proteins or chromatin marks mediate genomic contacts.]]>
Sat, 09 Jul 2016 00:00:00 PDT
Sequencing-based diagnostics for pediatric genetic diseases: progress and potential. Abou Tayoun A, Krock B, Spinner NB
Expert Rev Mol Diagn (Jul 2016)

The last two decades have witnessed revolutionary changes in clinical diagnostics, fueled by the Human Genome Project and advances in high throughput, Next Generation Sequencing (NGS). We review the current state of sequencing-based pediatric diagnostics, associated challenges, and future prospects.]]>
Fri, 08 Jul 2016 00:00:00 PDT
Nongenomic regulation of gene expression. Iglesias-Platas I, Monk D
Curr Opin Pediatr (Aug 2016)

The purpose of this review is to highlight the recent advances in epigenetic regulation and chromatin biology for a better understanding of gene regulation related to human disease.]]>
Thu, 07 Jul 2016 00:00:00 PDT
Evolutionary Patterns and Processes: Lessons from Ancient DNA. Leonardi M, Librado P, Der Sarkissian C, Schubert M, Alfarhan AH, Alquraishi SA, Al-Rasheid KA, Gamba C, Willerslev E, Orlando L
Syst Biol (Jul 2016)

Ever since its emergence in 1984, the field of ancient DNA has struggled to overcome the challenges related to the decay of DNA molecules in the fossil record. With the recent development of high-throughput DNA sequencing technologies and molecular techniques tailored to ultra-damaged templates, it has now come of age, merging together approaches in phylogenomics, population genomics, epigenomics and metagenomics. Leveraging on complete temporal sample series, ancient DNA provides direct access to the most important dimension in evolution - time, allowing a wealth of fundamental evolutionary processes to be addressed at unprecedented resolution. This review taps into the most recent findings in ancient DNA research to present analyses of ancient genomic and metagenomic data.]]>
Wed, 06 Jul 2016 00:00:00 PDT
Single-cell genome-wide bisulfite sequencing uncovers extensive heterogeneity in the mouse liver methylome. Gravina S, Dong X, Yu B, Vijg J
Genome Biol (2016)

Transmission fidelity of CpG DNA methylation patterns is not foolproof, with error rates from less than 1 to well over 10 % per CpG site, dependent on preservation of the methylated or unmethylated state and the type of sequence. This suggests a fairly high chance of errors. However, the consequences of such errors in terms of cell-to-cell variation have never been demonstrated by experimentally measuring intra-tissue heterogeneity in an adult organism.]]>
Wed, 06 Jul 2016 00:00:00 PDT
The harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins. Rouillard AD, Gundersen GW, Fernandez NF, Wang Z, Monteiro CD, McDermott MG, Ma'ayan A
Database (Oxford) (2016)

Genomics, epigenomics, transcriptomics, proteomics and metabolomics efforts rapidly generate a plethora of data on the activity and levels of biomolecules within mammalian cells. At the same time, curation projects that organize knowledge from the biomedical literature into online databases are expanding. Hence, there is a wealth of information about genes, proteins and their associations, with an urgent need for data integration to achieve better knowledge extraction and data reuse. For this purpose, we developed the Harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins from over 70 major online resources. We extracted, abstracted and organized data into ∼72 million functional associations between genes/proteins and their attributes. Such attributes could be physical relationships with other biomolecules, expression in cell lines and tissues, genetic associations with knockout mouse or human phenotypes, or changes in expression after drug treatment. We stored these associations in a relational database along with rich metadata for the genes/proteins, their attributes and the original resources. The freely available Harmonizome web portal provides a graphical user interface, a web service and a mobile app for querying, browsing and downloading all of the collected data. To demonstrate the utility of the Harmonizome, we computed and visualized gene-gene and attribute-attribute similarity networks, and through unsupervised clustering, identified many unexpected relationships by combining pairs of datasets such as the association between kinase perturbations and disease signatures. We also applied supervised machine learning methods to predict novel substrates for kinases, endogenous ligands for G-protein coupled receptors, mouse phenotypes for knockout genes, and classified unannotated transmembrane proteins for likelihood of being ion channels. The Harmonizome is a comprehensive resource of knowledge about genes and proteins, and as such, it enables researchers to discover novel relationships between biological entities, as well as form novel data-driven hypotheses for experimental validation.Database URL: http://amp.pharm.mssm.edu/Harmonizome.]]>
Mon, 04 Jul 2016 00:00:00 PDT
H19ICR mediated transcriptional silencing does not require target promoter methylation. Gebert C, Rong Q, Jeong S, Iben J, Pfeifer K
Biochem Biophys Res Commun (Jul 2016)

Transcription of the reciprocally imprinted genes Insulin-like growth factor 2 (Igf2) and H19 is orchestrated by the 2.4-kb H19 Imprinting Control Region (H19ICR) located upstream of H19. Three known functions are associated with the H19ICR: (1) it is a germline differentially methylated region, (2) it is a transcriptional insulator, and (3) it is a transcriptional silencer. The molecular mechanisms of the DMR and insulator functions have been well characterized but the basis for the ICR's silencer function is less well understood. In order to study the role the H19ICR intrinsically plays in gene silencing, we transferred the 2.4-kb H19ICR to a heterologous non-imprinted location on chromosome 5, upstream of the alpha fetoprotein (Afp) promoter. Independent of its orientation, the 2.4-kb H19ICR silences transcription from the paternal Afp promoter. Thus silencing is a function intrinsic to this DNA element. Further, ICR mediated silencing is a developmental process that, unexpectedly, does not occur through DNA methylation at the target promoter.]]>
Mon, 06 Jun 2016 00:00:00 PDT