'; ?> 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 Mon, 06 Jul 2020 05:32:09 EDT Mon, 06 Jul 2020 05:32:09 EDT jirtle@radonc.duke.edu james001@jirtle.com Bumblebee workers show differences in allele-specific DNA methylation and allele-specific expression. Marshall H, Jones ARC, Lonsdale ZN, Mallon EB
Genome Biol Evol (Jun 2020)

Allele-specific expression is when one allele of a gene shows higher levels of expression compared to the other allele, in a diploid organism. Recent work has identified allele-specific expression in a number of Hymenopteran species. However, the molecular mechanism which drives this allelic expression bias remains unknown. In mammals DNA methylation is often associated with genes which show allele-specific expression. DNA methylation systems have been described in species of Hymenoptera, providing a candidate mechanism. Using previously generated RNA-Seq and whole genome bisulfite sequencing from reproductive and sterile bumblebee (Bombus terrestris) workers we have identified genome-wide allele-specific expression and allele-specific DNA methylation. The majority of genes displaying allele-specific expression are common between reproductive and sterile workers and the proportion of allele-specific expression bias generally varies between genetically distinct colonies. We have also identified genome-wide allele-specific DNA methylation patterns in both reproductive and sterile workers, with reproductive workers showing significantly more genes with allele-specific methylation. Finally, there is no significant overlap between genes showing allele-specific expression and allele-specific methylation. These results indicate that cis-acting DNA methylation does not directly drive genome-wide allele-specific expression in this species.]]> Wed, 31 Dec 1969 19:00:00 EST CleanBSequences: an efficient curator of biological sequences in R. Pozzi FI, Green GY, Barbona IG, Rodríguez GR, Felitti SA
Mol Genet Genomics (Jul 2020)

This work presents a new method and tool to solve a common problem of molecular biologists and geneticists who use molecular markers in their scientific research and developments: curation of sequences. Omic studies conducted by molecular biologists and geneticists usually involve the use of molecular markers. AFLP, cDNA-AFLP, and MSAP are examples of markers that render information at the genomics, transcriptomics, and epigenomics levels, respectively. These three types of molecular markers use adaptors that are the template for PCR amplification. The sequences of the adaptors have to be eliminated for the analysis of the results. Since a large number of sequences are usually obtained in these studies, this clean-up of the data could demand long time and work. To automate this work, an R package, named CleanBSequences, was created that allows the sequences to be curated massively, quickly, without errors and can be used offline. The curating is performed by aligning the forward and/or reverse primers or ends of cloning vectors with the sequences to be removed. After the alignment, new subsequences are generated without biological fragments not desired by the user, i.e., sequences needed by the techniques. In conclusion, the CleanBSequences tool facilitates the work of researchers, reducing time, effort, and working errors. Therefore, the present tool would respond to the problems related to the curation of sequences obtained from the use of some types of molecular markers. In addition to the above, being an open source, CleanBSequences is a flexible tool that has the potential to be used in future improvements to respond to new problems.]]> Wed, 31 Dec 1969 19:00:00 EST Discovery of new epigenomics-based biomarkers and the early diagnosis of neurodegenerative diseases. Lee D, Choi YH, Seo J, Kim JK, Lee SB
Ageing Res Rev (Aug 2020)

Treatment options for many neurodegenerative diseases are limited due to the lack of early diagnostic procedures that allow timely delivery of therapeutic agents to affected neurons prior to cell death. While notable advances have been made in neurodegenerative disease biomarkers, whether or not the biomarkers discovered to date are useful for early diagnosis remains an open question. Additionally, the reliability of these biomarkers has been disappointing, due in part to the large dissimilarities between the tissues traditionally used to source biomarkers and primarily diseased neurons. In this article, we review the potential viability of atypical epigenetic and/or consequent transcriptional alterations (ETAs) as biomarkers of early-stage neurodegenerative disease, and present our perspectives on the discovery and practical use of such biomarkers in patient-derived neural samples using single-cell level analyses, thereby greatly enhancing the reliability of biomarker application.]]> Wed, 31 Dec 1969 19:00:00 EST The role of long non-coding RNAs in drug resistance of cancer. Zhang HD, Jiang LH, Zhong SL, Li J, Sun DW, Hou JC, Wang DD, Zhou SY, Tang JH
Clin Genet (Jun 2020)

Long non-coding RNAs (lncRNAs), a class of long RNAs, are longer than 200 nucleotides in length but lack protein-coding capacity. LncRNAs, as critical genomic regulators, are involved in genomic imprinting regulation, histone modification and gene expression regulation as well as tumor initiation and progression. However, it is also found that lncRNAs are associated with drug resistance in several types of cancer. Drug resistance is an important reason for clinical chemotherapy failure, and the molecular mechanism of tumor resistance is complex, which is a process of multi-cause, multi-gene and multi-signal transduction pathway interaction. Then comprehending the mechanisms of chemoresistance will help find ways to control the tumor progression effectively. Therefore, in this review, we will construct lncRNAs /drug resistance interaction network and shed light on the role of lncRNAs in drug resistance. This article is protected by copyright. All rights reserved.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenomic and transcriptional determinants of microglial cell identity. Gosselin D
Glia (Aug 2020)

Microglia perform multiple tasks that are essential to ensure proper cerebral functions, including synaptic remodeling, clearance of molecular debris, prevention of infections, and so forth. Furthermore, accumulating genetic and pathological evidence implicates microglial cell activity in the etiology of numerous neurodegenerative diseases and psychiatric disorders. Given this, efforts aimed at understanding the molecular mechanisms underlying microglial cell functions hold great potential for the development of novel therapies for various conditions affecting the central nervous system. In that regard, the application of paradigms in epigenomics to study transcription in microglia has provided significant insights into the molecular mechanisms that control the ontogeny and functions of these cells. With a focus on the roles of genomic regulatory elements and the epigenetic marks that control microglial gene expression, we review here recent key advancements in our comprehension of the epigenomic and transcriptional mechanisms that enable microglial cell development and activity.]]> Wed, 31 Dec 1969 19:00:00 EST What is new in the exposome? Vineis P, Robinson O, Chadeau-Hyam M, Dehghan A, Mudway I, Dagnino S
Environ Int (Jun 2020)

The exposome concept refers to the totality of exposures from a variety of external and internal sources including chemical agents, biological agents, or radiation, from conception onward, over a complete lifetime. It encompasses also "psychosocial components" including the impact of social relations and socio-economic position on health. In this review we provide examples of recent contributions from exposome research, where we believe their application will be of the greatest value for moving forward. So far, environmental epidemiology has mainly focused on hard outcomes, such as mortality, disease exacerbation and hospitalizations. However, there are many subtle outcomes that can be related to environmental exposures, and investigations can be facilitated by an improved understanding of internal biomarkers of exposure and response, through the application of omic technologies. Second, though we have a wealth of studies on environmental pollutants, the assessment of causality is often difficult because of confounding, reverse causation and other uncertainties. Biomarkers and omic technologies may allow better causal attribution, for example using instrumental variables in triangulation, as we discuss here. Even more complex is the understanding of how social relationships (in particular socio-economic differences) influence health and imprint on the fundamental biology of the individual. The identification of molecular changes that are intermediate between social determinants and disease status is a way to fill the gap. Another field in which biomarkers and omics are relevant is the study of mixtures. Epidemiology often deals with complex mixtures (e.g. ambient air pollution, food, smoking) without fully disentangling the compositional complexity of the mixture, or with rudimentary approaches to reflect the overall effect of multiple exposures or components. From the point of view of disease mechanisms, most models hypothesize that several stages need to be transitioned through health to the induction of disease, but very little is known about the characteristics and temporal sequence of such stages. Exposome models reinforce the idea of a biography-to-biology transition, in that everyone's disease is the product of the individual history of exposures, superimposed on their underlying genetic susceptibilities. Finally, exposome research is facilitated by technological developments that complement traditional epidemiological study designs. We describe in depth one such new tools, adductomics. In general, the development of high-resolution and high-throughput technologies interrogating multiple -omics (such as epigenomics, transcriptomics, proteomics, adductomics and metabolomics) yields an unprecedented perspective into the impact of the environment in its widest sense on disease. The world of the exposome is rapidly evolving, though a huge gap still needs to be filled between the original expectations and the concrete achievements. Perhaps the most urgent need is for the establishment of a new generation of cohort studies with appropriately specified biosample collection, improved questionnaire data (including social variables), and the deployment of novel technologies that allow better characterization of individual environmental exposures, ranging from personal monitoring to satellite based observations.]]> Wed, 31 Dec 1969 19:00:00 EST Capturing functional epigenomes for insight into metabolic diseases. Allum F, Grundberg E
Mol Metab (Aug 2020)

Metabolic diseases such as obesity are known to be driven by both environmental and genetic factors. Although genome-wide association studies of common variants and their impact on complex traits have provided some biological insight into disease etiology, identified genetic variants have been found to contribute only a small proportion to disease heritability, and to map mainly to non-coding regions of the genome. To link variants to function, association studies of cellular traits, such as epigenetic marks, in disease-relevant tissues are commonly applied.]]> Wed, 31 Dec 1969 19:00:00 EST Molecular bases of responses to abiotic stress in trees. Estravis-Barcala M, Mattera MG, Soliani C, Bellora N, Opgenoorth L, Heer K, Arana MV
J Exp Bot (Jun 2020)

Trees are constantly exposed to climate fluctuations, which vary with both time and geographic location. Environmental changes that are outside of the physiological favorable range usually negatively affect plant performance and trigger responses to abiotic stress. Long-living trees in particular have evolved a wide spectrum of molecular mechanisms to coordinate growth and development under stressful conditions, thus minimizing fitness costs. The ongoing development of techniques directed at quantifying abiotic stress has significantly increased our knowledge of physiological responses in woody plants. However, it is only within recent years that advances in next-generation sequencing and biochemical approaches have enabled us to begin to understand the complexity of the molecular systems that underlie these responses. Here, we review recent progress in our understanding of the molecular bases of drought and temperature stresses in trees, with a focus on functional, transcriptomic, epigenetic, and population genomic studies. In addition, we highlight topics that will contribute to progress in our understanding of the plastic and adaptive responses of woody plants to drought and temperature in a context of global climate change.]]> Wed, 31 Dec 1969 19:00:00 EST IMPLICON: an ultra-deep sequencing method to uncover DNA methylation at imprinted regions. Klobučar T, Kreibich E, Krueger F, Arez M, Pólvora-Brandão D, von Meyenn F, da Rocha ST, Eckersley-Maslin M
Nucleic Acids Res (Jul 2020)

Genomic imprinting is an epigenetic phenomenon leading to parental allele-specific expression. Dosage of imprinted genes is crucial for normal development and its dysregulation accounts for several human disorders. This unusual expression pattern is mostly dictated by differences in DNA methylation between parental alleles at specific regulatory elements known as imprinting control regions (ICRs). Although several approaches can be used for methylation inspection, we lack an easy and cost-effective method to simultaneously measure DNA methylation at multiple imprinted regions. Here, we present IMPLICON, a high-throughput method measuring DNA methylation levels at imprinted regions with base-pair resolution and over 1000-fold coverage. We adapted amplicon bisulfite-sequencing protocols to design IMPLICON for ICRs in adult tissues of inbred mice, validating it in hybrid mice from reciprocal crosses for which we could discriminate methylation profiles in the two parental alleles. Lastly, we developed a human version of IMPLICON and detected imprinting errors in embryonic and induced pluripotent stem cells. We also provide rules and guidelines to adapt this method for investigating the DNA methylation landscape of any set of genomic regions. In summary, IMPLICON is a rapid, cost-effective and scalable method, which could become the gold standard in both imprinting research and diagnostics.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic regulation in the pathophysiology of Lewy body dementia. Chouliaras L, Kumar GS, Thomas AJ, Lunnon K, Chinnery PF, O'Brien JT
Prog Neurobiol (Sep 2020)

Lewy body dementia encompasses both dementia with Lewy bodies and Parkinson's disease dementia. Although both are common causes of dementia, they remain relatively understudied. The review summarises the clinico-pathologic characteristics of Lewy Body dementia and discusses the genetic and environmental evidence contributing to the risk of developing the condition. Considering that the pathophysiology of Lewy body dementia is not yet fully understood, here we focus on the role of epigenetic mechanisms as potential key mediators of gene-environment interactions in the development of the disease. We examine available important data on genomics, epigenomics, gene expression and proteomic studies in Lewy body dementia on human post-mortem brain and peripheral tissues. Genetic variation and epigenetic modifications in key genes involved in the disorder, such as apolipoprotein E (APOE), α-synuclein (SNCA) and glucocerobrosidase (GBA), suggest a central involvement of epigenetics in DLB but conclusive evidence is scarce. This is due to limitations of existing literature, such as small sample sizes, lack of replication and lack of studies interrogating cell-type specific epigenetic modifications in the brain. Future research in the field can improve the understanding of this common but complex and rapidly progressing type of dementia and potentially open early diagnostic and effective therapeutic targets.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenomics and genotype-phenotype association analyses reveal conserved genetic architecture of complex traits in cattle and human. Liu S, Yu Y, Zhang S, Cole JB, Tenesa A, Wang T, McDaneld TG, Ma L, Liu GE, Fang L
BMC Biol (Jul 2020)

Lack of comprehensive functional annotations across a wide range of tissues and cell types severely hinders the biological interpretations of phenotypic variation, adaptive evolution, and domestication in livestock. Here we used a combination of comparative epigenomics, genome-wide association study (GWAS), and selection signature analysis, to shed light on potential adaptive evolution in cattle.]]> Wed, 31 Dec 1969 19:00:00 EST How to improve mouse cloning. Ogura A
Theriogenology (Jul 2020)

The mouse is the most extensively used mammalian laboratory species in biology and medicine because of the ready availability of a wide variety of defined genetic and gene-modified strains and abundant genetic information. Its small size and rapid generation turnover are also advantages compared with other experimental animals. Using these advantages, somatic cell nuclear transfer (SCNT) in mice has provided invaluable information on epigenetics related to SCNT technology and cloning, playing a leading role in relevant technical improvements. These improvements include treatment with histone deacetylase inhibitors, correction of Xist gene expression (controlling X chromosome inactivation), and removal of methylated histones from SCNT-generated embryos, which have proven to be effective for SCNT cloning of other species. However, even with the best combination of these treatments, the birth rate in cloned offspring is still lower than intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF). One remaining issue associated with SCNT is placental enlargement (hyperplasia) found in late pregnancy, but this abnormality might not be a major cause for the low efficiency of SCNT because many SCNT-derived embryos die before their placentas start to enlarge at midgestation (early postimplantation stage). It is known that, at this stage, undifferentiated trophoblast cells in the extraembryonic tissue of SCNT-derived embryos fail to proliferate. Understanding the molecular mechanisms is essential for further technical improvements of mouse SCNT, which might also provide clues for technical breakthroughs in mammalian SCNT and cloning in general.]]> Wed, 31 Dec 1969 19:00:00 EST Association of DNA sequence-independent genetic regulatory mechanisms with apical periodontitis: A scoping review. Adeodato CSR, Alves GG, Botelho AMN, Caldas IP, Gonçalves FP, Pinto LFR, Lima SCS, Fagundes MCN, Masterson D, Scelza P, Scelza MFZ
Arch Oral Biol (Jul 2020)

Different studies in the last decade have proposed that gene expression alterations that are independent of the DNA sequence may also play an important role in periapical disease. The present study aimed to assess the available evidence supporting a relationship between these alterations and apical periodontitis through a scoping review.]]> Wed, 31 Dec 1969 19:00:00 EST Lineage and parent-of-origin effects in DNA methylation of honey bees (Apis mellifera) revealed by reciprocal crosses and whole-genome bisulfite sequencing. Wu X, Galbraith DA, Chatterjee P, Jeong H, Grozinger CM, Yi SV
Genome Biol Evol (Jun 2020)

Parent-of-origin methylation arises when the methylation patterns of a particular allele is dependent on the parent it was inherited from. Previous work in honey bees has shown evidence of parent-of-origin specific expression, yet the mechanisms regulating such pattern remains unknown in honey bees. In mammals and plants, DNA methylation is known to regulate parent-of-origin effects such as genomic imprinting. Here, we utilize genotyping of reciprocal European and Africanized honey bee crosses to study genome-wide allele-specific methylation patterns in sterile and reproductive individuals. Our data confirms the presence of allele-specific methylation in honey bees in lineage-specific contexts but also importantly, though to a lesser degree, parent-of-origin contexts. We show that the majority of allele-specific methylation occur due to lineage rather than parent-of-origin factors, regardless of reproductive state. Interestingly, genes affected by allele-specific DNA methylation often exhibit both lineage and parent-of-origin effects, indicating that they are particularly labile in terms of DNA methylation patterns. Additionally, we re-analyzed our previous study on parent-of-origin specific expression in honey bees and found little association with parent-of-origin specific methylation. These results indicate strong genetic background effects on allelic DNA methylation, and suggest that while parent-of-origin effects are manifested in both DNA methylation and gene expression, they are not directly associated with each other.]]> Wed, 31 Dec 1969 19:00:00 EST Diagnostic testing for uniparental disomy: a points to consider statement from the American College of Medical Genetics and Genomics (ACMG). Del Gaudio D, Shinawi M, Astbury C, Tayeh MK, Deak KL, Raca G,  
Genet Med (Jul 2020)

]]> Wed, 31 Dec 1969 19:00:00 EST Regulation of Inflammation in Diabetes: from Genetics to EpiGenomics Evidence. Diedisheim M, Carcarino E, Vandiedonck C, Roussel R, Jean-François G, Venteclef N
Mol Metab (Jun 2020)

Diabetes is one of the greatest public health challenges worldwide, and we still lack complementary approaches to significantly enhance the efficacy of preventive and therapeutic approaches. Genetic and environmental factors are the culprits involved in diabetes risk. Evidence from the last decade has highlighted that deregulation in the immune and inflammatory responses increase susceptibility to type 1 and type 2 diabetes. Spatiotemporal patterns of gene expression involved in immune cell polarisation depend on genomic enhancer elements in response to inflammatory and metabolic cues. Several studies have reported that most regulatory genetic variants are located in the non-protein coding part regions of the genome and particularly in enhancer regions. The progress of high-throughput technologies has permitted the characterization of enhancer chromatin properties. These advances support the concept that genetic alteration of enhancers may influence the immune and inflammatory responses in relation with diabetes.]]> Wed, 31 Dec 1969 19:00:00 EST The impact of sex differences on genomic research. Oertelt-Prigione S, Mariman E
Int J Biochem Cell Biol (07 2020)

Sex and gender differences affect all dimensions of human health ranging from the biological basis of disease to therapeutic access, choice and response. Genomics research has long ignored the role of sex differences as potential modulators and the concept is gaining more attention only recently. In the present review we summarize the current knowledge of the impact of sex differences on genomic and epigenomic research, the potential interaction of genomics and gender and the role of these differences in disease etiopathogenesis. Sex differences can emerge from differences in the sex chromosomes themselves, from their interaction with the genome and from the influence of hormones on genomic processes. The impact of these processes on the incidence of autoimmune and oncologic disease is well documented. The growing field of systems biology, which aims at integrating information from different networks of the human body, could also greatly benefit from this approach. In the present review we summarize the current knowledge and provide recommendations for the future performance of sex-sensitive genomics research.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenome-450K-wide methylation signatures of active cigarette smoking: the Young Finns Study. Mishra PP, Hänninen I, Raitoharju E, Marttila S, Mishra BH, Mononen N, Kähönen M, Hurme M, Raitakari O, Törönen P, Holm L, Lehtimäki T
Biosci Rep (Jun 2020)

Smoking as a major risk factor for morbidity affects numerous regulatory systems of the human body including DNA methylation. Most of the previous studies with genome-wide methylation data are based on conventional association analysis and earliest threshold-based gene set analysis which lacks sensitivity to be able to reveal all the relevant effects of smoking. The aim of this study was to investigate impact of active smoking on DNA methylation at three biological levels: 5'-C-phosphate-G-3' (CpG) sites, genes and functionally related genes (gene sets). Gene set analysis was done with mGSZ, a modern threshold-free method previously developed by us that utilizes all the genes in the experiment and their differential methylation scores. Application of such method in DNA methylation study is novel. Epigenome-wide methylation levels were profiled from Young Finns Study (YFS) participants' whole blood from 2011 follow-up using Illumina Infinium HumanMethylation450 BeadChips. We identified three novel smoking related CpG sites and replicated 57 of the previously identified ones. We found that smoking is associated with hypomethylation in shore (genomic regions 0-2 kilobases from CpG island). We identified smoking related methylation changes in 13 gene sets with false discovery rate (fdr) , among which is olfactory receptor activity, the flagship novel finding of this study. Overall, we extended the current knowledge by identifying: i) three novel smoking related CpG sites, ii) similar effects as ageing on average methylation in shore, and iii) a novel finding that olfactory receptor activity pathway responds to tobacco smoke and toxin exposure through epigenetic mechanisms.]]> Wed, 31 Dec 1969 19:00:00 EST Transcriptional memory in skeletal muscle. Don't forget (to) exercise. Beiter T, Nieß AM, Moser D
J Cell Physiol (Jul 2020)

Transcriptional memory describes an ancient and highly conserved form of cellular learning that enables cells to benefit from recent experience by retaining a mitotically inheritable but reversible memory of the initial transcriptional response when encountering an environmental or physiological stimulus. Herein, we will review recent progress made in the understanding of how cells can make use of diverse constituents of the epigenetic toolbox to retain a transcriptional memory of past states and perturbations. Specifically, we will outline how these mechanisms will help to improve our understanding of skeletal muscle plasticity in health and disease. We describe the epigenetic road map that allows skeletal muscle fibers to navigate through training-induced adaptation processes, and how epigenetic memory marks can preserve an autobiographical history of lifestyle behavior changes, pathological challenges, and aging. We will further consider some key findings in the field of exercise epigenomics to emphasize major challenges when interpreting dynamic changes in the chromatin landscape in response to acute exercise and training.]]> Wed, 31 Dec 1969 19:00:00 EST Power of proteomics and progress in precision medicine - 13th central and eastern European proteomic conference (CEEPC), Ustroń, Poland. Gadher SJ, Widlak P, Kovarova H
Expert Rev Proteomics (Jun 2020)

Central and Eastern European Proteomic Conference (CEEPC) provides a platform for researchers to discuss multi-disciplinary integrated approaches to address a range of challenges from present day viral pandemic to on-going progress in Precision Medicine. CEEPC brings together various multi-omics entwined with novel enabling technologies, thus facilitating conceptual advances from cell to society for the benefit of mankind.]]> Wed, 31 Dec 1969 19:00:00 EST