'; ?> 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 Sat, 16 Nov 2019 17:08:52 EST Sat, 16 Nov 2019 17:08:52 EST jirtle@radonc.duke.edu james001@jirtle.com RNA sequencing of identical twins discordant for autism reveals blood-based signatures implicating immune and transcriptional dysregulation. Saffari A, Arno M, Nasser E, Ronald A, Wong CCY, Schalkwyk LC, Mill J, Dudbridge F, Meaburn EL
Mol Autism (2019)

A gap exists in our mechanistic understanding of how genetic and environmental risk factors converge at the molecular level to result in the emergence of autism symptoms. We compared blood-based gene expression signatures in identical twins concordant and discordant for autism spectrum condition (ASC) to differentiate genetic and environmentally driven transcription differences, and establish convergent evidence for biological mechanisms involved in ASC.]]>
Wed, 31 Dec 1969 19:00:00 EST
The concept of the hologenome, an epigenetic phenomenon, challenges aspects of the modern evolutionary synthesis. Collens A, Kelley E, Katz LA
J Exp Zool B Mol Dev Evol (Nov 2019)

John Tyler Bonner's call to re-evaluate evolutionary theory in light of major transitions in life on Earth (e.g., from the first origins of microbial life to the evolution of sex, and the origins of multicellularity) resonate with recent discoveries on epigenetics and the concept of the hologenome. Current studies of genome evolution often mistakenly focus only on the inheritance of DNA between parent and offspring. These are in line with the widely accepted Neo-Darwinian framework that pairs Mendelian genetics with an emphasis on natural selection as explanations for the evolution of biodiversity on Earth. Increasing evidence for widespread symbioses complicates this narrative, as is seen in Scott Gilbert's discussion of the concept of the holobiont in this series: Organisms across the tree of life coexist with substantial influence on one another through endosymbiosis, symbioses, and host-associated microbiomes. The holobiont theory, coupled with observations from molecular studies, also requires us to understand genomes in a new way-by considering the interactions underlain by the genome of a host plus its associated microbes, a conglomerate entity referred to as the hologenome. We argue that the complex patterns of inheritance of these genomes coupled with the influence of symbionts on host gene expression make the concept of the hologenome an epigenetic phenomenon. We further argue that the aspects of the hologenome challenge of the modern evolutionary synthesis, which requires updating to remain consistent with Darwin's intent of providing natural laws that underlie the evolution of life on Earth.]]>
Wed, 31 Dec 1969 19:00:00 EST
Genome-Wide Identification of Allele-Specific Gene Expression in a Parent-of-Origin Specific Manner. Chen C, Begcy K
Methods Mol Biol (2020)

Upon fertilization, normal endosperm and embryo development require the contribution of both the maternal and paternal genomes. However, certain genes are expressed in a parent-of-origin-dependent manner, an epigenetic phenomenon known as genomic imprinting. Despite the blast of new technologies and the crucial advances of the past decades in the epigenetics field, novel imprinted genes are yet to be discovered and thus key regulators of early seed development. Using rice plant as a model, we describe a method for the identification of imprinted genes based on an RNA-Seq approach, which allows the identification of maternal and paternal gene expression in a parent-of-origin-specific manner.]]>
Wed, 31 Dec 1969 19:00:00 EST
Direct prediction of regulatory elements from partial data without imputation. Zhang Y, Mahony S
PLoS Comput Biol (Nov 2019)

Genome segmentation approaches allow us to characterize regulatory states in a given cell type using combinatorial patterns of histone modifications and other regulatory signals. In order to analyze regulatory state differences across cell types, current genome segmentation approaches typically require that the same regulatory genomics assays have been performed in all analyzed cell types. This necessarily limits both the numbers of cell types that can be analyzed and the complexity of the resulting regulatory states, as only a small number of histone modifications have been profiled across many cell types. Data imputation approaches that aim to estimate missing regulatory signals have been applied before genome segmentation. However, this approach is computationally costly and propagates any errors in imputation to produce incorrect genome segmentation results downstream. We present an extension to the IDEAS genome segmentation platform which can perform genome segmentation on incomplete regulatory genomics dataset collections without using imputation. Instead of relying on imputed data, we use an expectation-maximization approach to estimate marginal density functions within each regulatory state. We demonstrate that our genome segmentation results compare favorably with approaches based on imputation or other strategies for handling missing data. We further show that our approach can accurately impute missing data after genome segmentation, reversing the typical order of imputation/genome segmentation pipelines. Finally, we present a new 2D genome segmentation analysis of 127 human cell types studied by the Roadmap Epigenomics Consortium. By using an expanded set of chromatin marks that have been profiled in subsets of these cell types, our new segmentation results capture a more complex picture of combinatorial regulatory patterns that appear on the human genome.]]>
Wed, 31 Dec 1969 19:00:00 EST
Genome-Wide Profiling of Histone Modifications with ChIP-Seq. Ricci WA, Levin L, Zhang X
Methods Mol Biol (2020)

Chromatin immunoprecipitation coupled with sequencing (ChIP-seq) is a widely used method for mapping the genome-wide locations of chromatin-associated proteins. This protocol has been developed and utilized to perform ChIP on histone covalent modifications in various plant species including cereals. DNA and chromatin-associated proteins are crosslinked with formaldehyde. Chromatin is then isolated from nuclei and sheared via sonication. Antibodies targeting the histone modification of interest are incubated with the sheared chromatin and nonspecific interactions are washed away. DNA is purified via phenol-chloroform extraction, end-repaired, ligated to sequencing adapters, and PCR-amplified.]]>
Wed, 31 Dec 1969 19:00:00 EST
Role of epigenetics in alveolar bone resorption and regeneration around periodontal and peri-implant tissues. Asa'ad F, Monje A, Larsson L
Eur J Oral Sci (Nov 2019)

Periodontitis and peri-implantitis are multifactorial diseases characterized by alveolar bone destruction mediated by the host response to a microbial challenge. Alveolar bone resorption mediated by epigenetics could be one of the mechanisms responsible for this destruction of alveolar bone. The relationship between epigenetic modifications and bone metabolism has been thoroughly investigated in bone remodeling, cancer, and rheumatoid arthritis, but evidence is low regarding the relationship between epigenetic modifications and alveolar bone loss related to periodontal and peri-implant diseases. Therefore, we conducted a review of the pertinent literature based on a priori-formulated focused questions and a screening strategy, in an attempt to comprehend the role of different epigenetic mechanisms in alveolar bone loss and to determine the current state with respect to their possible therapeutic applications in regenerative medicine. The review showed that the roles of DNA methylation, histone modifications, and non-coding RNAs in bone loss have been investigated. The results indicate that epigenetic mechanisms can participate in periodontal and peri-implant alveolar bone breakdown, suggesting their potential as therapeutic targets in alveolar bone regeneration. However, there is still only preliminary information regarding the possible therapeutic utility of these epigenetic mechanisms, suggesting a need for basic and translational research to assess the potential of such mechanisms in promoting alveolar bone regeneration.]]>
Wed, 31 Dec 1969 19:00:00 EST
Next generation sequencing data for use in risk assessment. Merrick BA
Curr Opin Toxicol (Dec 2019)

Next generation sequencing (NGS) represents several powerful platforms that have revolutionized RNA and DNA analysis. The parallel sequencing of millions of DNA molecules can provide mechanistic insights into toxicology and provide new avenues for biomarker discovery with growing relevance for risk assessment. The evolution of NGS technologies has improved over the last decade with increased sensitivity and accuracy to foster new biomarker assays from tissue, blood and other biofluids. NGS sequencing technologies can identify transcriptional changes and genomic targets with base pair precision in response to chemical exposure. Further, there are several exciting movements within the toxicology community that incorporate NGS platforms into new strategies for more rapid toxicological characterizations. These include the Tox21 in vitro high throughput transcriptomic screening program, development of organotypic spheroids, alternative animal models, mining archival tissues, liquid biopsy and epigenomics. This review will describe NGS-based technologies, demonstrate how they can be used as tools for target discovery in tissue and blood, and suggest how they might be applied for risk assessment.]]>
Wed, 31 Dec 1969 19:00:00 EST
Characterization of Button Loci that Promote Homologous Chromosome Pairing and Cell-Type-Specific Interchromosomal Gene Regulation. Viets K, Sauria MEG, Chernoff C, Rodriguez Viales R, Echterling M, Anderson C, Tran S, Dove A, Goyal R, Voortman L, Gordus A, Furlong EEM, Taylor J, Johnston RJ
Dev Cell (Nov 2019)

Homologous chromosomes colocalize to regulate gene expression in processes including genomic imprinting, X-inactivation, and transvection. In Drosophila, homologous chromosomes pair throughout development, promoting transvection. The "button" model of pairing proposes that specific regions along chromosomes pair with high affinity. Here, we identify buttons interspersed across the fly genome that pair with their homologous sequences, even when relocated to multiple positions in the genome. A majority of transgenes that span a full topologically associating domain (TAD) function as buttons, but not all buttons contain TADs. Additionally, buttons are enriched for insulator protein clusters. Fragments of buttons do not pair, suggesting that combinations of elements within a button are required for pairing. Pairing is necessary but not sufficient for transvection. Additionally, pairing and transvection are stronger in some cell types than in others, suggesting that pairing strength regulates transvection efficiency between cell types. Thus, buttons pair homologous chromosomes to facilitate cell-type-specific interchromosomal gene regulation.]]>
Wed, 31 Dec 1969 19:00:00 EST
Altered expression of epigenetic regulators and imprinted genes in human placenta and fetal tissues from second trimester spontaneous pregnancy losses. Vasconcelos S, Ramalho C, Marques CJ, Doria S
Epigenetics (Dec 2019)

Epigenetic mechanisms such as genomic imprinting have a fundamental role in embryo and fetal development. Hence, we here studied expression levels of epigenetic modifiers and imprinted genes in cases of ididopathic spontaneous abortion (SA). Thirty-five placental samples and 35 matched fetal tissues from second trimester SA were analysed; including 16 controls (placental and fetal infections as the known cause of spontaneous abortion) and 19 idiopathic SA cases. Transcript levels of epigenetic regulators and imprinted genes were measured by qRT-PCR and methylation at imprinted genes was studied by bisulfite genomic sequencing and MS-MLPA. Global DNA hydroxymethylation (5-hmC) levels were measured by an ELISA-based assay. We observed an upregulation of and in placental samples from idiopathic SA cases; however, no significant difference in global 5-hmC levels was observed. On the contrary, in fetal tissues, was markedly downregulated in idiopathic SA, showing an opposite trend to that observed in placental tissue. and were upregulated and downregulated in placentas from idiopathic SA cases; concordantly, was also upregulated in fetal tissues from idiopathic SA cases. Although not reaching statistical significance, an increase in methylation levels of , KvDMR1 and H19 DMRs was observed in idiopathic SA cases, concordantly with the observed changes in expression. Our study reveals, for the first time, deregulation of epigenetic modifiers and imprinted genes in both placental and fetal tissues from idiopathic SA cases in the second trimester of pregnancy, indicating a critical role during pregnancy.]]>
Wed, 31 Dec 1969 19:00:00 EST
The systems medicine of neonatal abstinence syndrome. Stone WL, Wood DL, Justice NA, Shah DS, Olsen ME, Bharti D
Front Biosci (Landmark Ed) (Jan 2020)

This review will focus on a systems medicine approach to neonatal abstinence syndrome (NAS). Systems medicine utilizes information gained from the application of "omics" technology and bioinformatics (1). The omic approaches we will emphasize include genomics, epigenomics, proteomics, and metabolomics. The goals of systems medicine are to provide clinically relevant and objective insights into disease diagnosis, prognosis, and stratification as well as pharmacological strategies and evidence-based individualized clinical guidance. Despite the increasing incidence of NAS and its societal and economic costs, there has been only a very modest emphasis on utilizing a systems medicine approach, and this has been primarily in the areas of genomics and epigenomics. As detailed below, proteomics and metabolomics hold great promise in advancing our knowledge of NAS and its treatment. Metabolomics, in particular, can provide a quantitative assessment of the exposome, which is a comprehensive picture of both internal and external environmental factors affecting health.]]>
Wed, 31 Dec 1969 19:00:00 EST
Development of an Interactive Web Application "Shiny App for Frequency Analysis on Homo sapiens Genome (SAFA-HsG)". Sivaprakasam B, Sadagopan P
Interdiscip Sci (Dec 2019)

The web application "Shiny App for Frequency Analysis on Homo sapiens Genome (SAFA-HsG)" was developed using R programming-based bioconductor packages and shiny framework. Through the app, preliminary descriptive data analysis on nucleotide frequency, and CpG island, CpG non-island, and CpG island shores and shelves (downstream and upstream) of human reference genome can be carried out, which will help biologists to work on human epigenomics. Table view of these analyses of all chromosomes can be visualized and downloaded by the end users. Similarly, the respective comparative plots can be used for CpG sites comparison. In addition, to introduce the personal genome project, the present study has done a preliminary work on few raw data and are included in the app, which will create interest on personal genome information. The app is hosted on https://SAFA-HsG.shinyapps.io/home/. It is a multi-platform application and can be initiated locally from any computer that has or has not installed R. It is a user-friendly interface, which will allow a biologist, even who has little computer knowledge to access and analyze further.]]>
Wed, 31 Dec 1969 19:00:00 EST
Development of a method for identifying and functionally analyzing allele-specific DNA methylation based on BS-seq data. Zhu J, Su M, Gu Y, Zhang X, Lv W, Zhang S, Sun Z, Lu H, Zhang Y
Epigenomics (Nov 2019)

To comprehensively identify allele-specific DNA methylation (ASM) at the genome-wide level. Here, we propose a new method, called GeneASM, to identify ASM using high-throughput bisulfite sequencing data in the absence of haplotype information. A total of 2194 allele-specific DNA methylated genes were identified in the GM12878 lymphocyte lineage using GeneASM. These genes are mainly enriched in cell cytoplasm function, subcellular component movement or cellular linkages. GM12878 methylated DNA immunoprecipitation sequencing, and methylation sensitive restriction enzyme sequencing data were used to evaluate ASM. The relationship between ASM and disease was further analyzed using the The Cancer Genome Atlas (TCGA) data of lung adenocarcinoma (LUAD), and whole genome bisulfite sequencing data. GeneASM, which recognizes ASM by high-throughput bisulfite sequencing and heterozygous single-nucleotide polymorphisms, provides new perspective for studying genomic imprinting.]]>
Wed, 31 Dec 1969 19:00:00 EST
Biological underpinnings from psychosocial stress towards appetite and obesity during youth: research implications towards metagenomics, epigenomics and metabolomics. Michels N
Nutr Res Rev (Dec 2019)

Psychosocial stress, uncontrolled eating and obesity are three interrelated epidemiological phenomena already present during youth. This broad narrative conceptual review summarises main biological underpinnings of the stress-diet-obesity pathway and how new techniques can further knowledge. Cortisol seems the main biological factor from stress towards central adiposity; and diet, physical activity and sleep are the main behavioural pathways. Within stress-diet, the concepts of comfort food and emotional eating are highlighted, as cortisol affects reward pathways and appetite brain centres with a role for insulin, leptin, neuropeptide Y (NPY), endocannabinoids, orexin and gastrointestinal hormones. More recently researched biological underpinnings are microbiota, epigenetic modifications and metabolites. First, the gut microbiota reaches the stress-regulating and appetite-regulating brain centres via the gut-brain axis. Second, epigenetic analyses are recommended as diet, obesity, stress and gut microbiota can change gene expression which then affects appetite, energy homeostasis and stress reactivity. Finally, metabolomics would be a good technique to disentangle stress-diet-obesity interactions as multiple biological pathways are involved. Saliva might be an ideal biological matrix as it allows metagenomic (oral microbiota), epigenomic and metabolomic analyses. In conclusion, stress and diet/obesity research should be combined in interdisciplinary collaborations with implementation of several -omics analyses.]]>
Wed, 31 Dec 1969 19:00:00 EST
Treatment with JQ1, a BET bromodomain inhibitor, is selectively detrimental to R6/2 Huntington's disease mice. Kedaigle AJ, Reidling JC, Lim RG, Adam M, Wu J, Wassie B, Stocksdale JT, Casale MS, Fraenkel E, Thompson LM
Hum Mol Genet (Nov 2019)

Transcriptional and epigenetic alterations occur early in Huntington's disease (HD) and treatment with epigenetic modulators are beneficial in several HD animal models. The drug JQ1, which inhibits histone acetyl-lysine reader bromodomains, has shown promise in multiple cancers and in neurodegenerative disease. We tested whether JQ1 could improve behavioral phenotypes in the R6/2 mouse model of HD and modulate HD-associated changes in transcription and epigenomics. R6/2 and non-transgenic (NT) mice were treated with JQ1 daily from 5-11 weeks of age and behavioral phenotypes evaluated over this period. Following the trial, cortex and striatum were isolated and subjected to mRNA-seq and ChIP-seq for the histone marks H3K4me3 and H3K27ac. Initially, JQ1 enhanced motor performance in NT mice. In R6/2 mice, however, JQ1 had no effect on rotarod or grip strength but exacerbated weight loss and worsened performance on the pole test. JQ1-induced gene expression changes in NT mice were distinct from those in R6/2 and primarily involved protein translation and bioenergetics pathways. Dysregulation of HD-related pathways in striatum was exacerbated by JQ1 in R6/2 mice, but not in NTs, and JQ1 caused a corresponding increase in the formation of a mutant huntingtin protein-dependent High Molecular Weight (HMW) species associated with pathogenesis. This study suggests that drugs predicted to be beneficial based on their mode of action and effects in wild-type or in other neurodegenerative disease models may have an altered impact in the HD context. These observations have important implications in the development of epigenetic modulators as therapies for HD.]]>
Wed, 31 Dec 1969 19:00:00 EST
Pan-cancer clinical and molecular analysis of racial disparities. Lara OD, Wang Y, Asare A, Xu T, Chiu HS, Liu Y, Hu W, Sumazin P, Uppal S, Zhang L, Rauh-Hain JA, Sood AK
Cancer (Nov 2019)

Racial disparities in cancer outcomes are increasingly recognized, but comprehensive analyses, including molecular studies, are limited. The objective of the current study was to perform a pan-cancer clinical and epigenetic molecular analysis of outcomes in African American (AA) and European American (EA) patients.]]>
Wed, 31 Dec 1969 19:00:00 EST
In-utero stress and mode of conception: impact on regulation of imprinted genes, fetal development and future health. Argyraki M, Damdimopoulou P, Chatzimeletiou K, Grimbizis GF, Tarlatzis BC, Syrrou M, Lambropoulos A
Hum Reprod Update (Nov 2019)

Genomic imprinting is an epigenetic gene regulatory mechanism; disruption of this process during early embryonic development can have major consequences on both fetal and placental development. The periconceptional period and intrauterine life are crucial for determining long-term susceptibility to diseases. Treatments and procedures in assisted reproductive technologies (ART) and adverse in-utero environments may modify the methylation levels of genomic imprinting regions, including insulin-like growth factor 2 (IGF2)/H19, mesoderm-specific transcript (MEST), and paternally expressed gene 10 (PEG10), affecting the development of the fetus. ART, maternal psychological stress, and gestational exposures to chemicals are common stressors suspected to alter global epigenetic patterns including imprinted genes.]]>
Wed, 31 Dec 1969 19:00:00 EST
Harnessing targeted DNA methylation and demethylation using dCas9. Pflueger C, Swain T, Lister R
Essays Biochem (Nov 2019)

DNA methylation is an essential DNA modification that plays a crucial role in genome regulation during differentiation and development, and is disrupted in a range of disease states. The recent development of CRISPR/catalytically dead CRISPR/Cas9 (dCas9)-based targeted DNA methylation editing tools has enabled new insights into the roles and functional relevance of this modification, including its importance at regulatory regions and the role of aberrant methylation in various diseases. However, while these tools are advancing our ability to understand and manipulate this regulatory layer of the genome, they still possess a variety of limitations in efficacy, implementation, and targeting specificity. Effective targeted DNA methylation editing will continue to advance our fundamental understanding of the role of this modification in different genomic and cellular contexts, and further improvements may enable more accurate disease modeling and possible future treatments. In this review, we discuss strategies, considerations, and future directions for targeted DNA methylation editing.]]>
Wed, 31 Dec 1969 19:00:00 EST
Museum epigenomics: characterizing cytosine methylation in historic museum specimens. Rubi TL, Knowles LL, Dantzer B
Mol Ecol Resour (Nov 2019)

Museum genomics has transformed the field of collections-based research, opening up a range of new research directions for paleontological specimens as well as natural history specimens collected over the past few centuries. Recent work demonstrates that it is possible to characterize epigenetic markers such as DNA methylation in well-preserved ancient tissues. This approach has not yet been tested in traditionally-prepared natural history specimens such as dried bones and skins, the most common specimen types in vertebrate collections. In this study, we develop and test methods to characterize cytosine methylation in dried skulls up to 76 years old. Using a combination of ddRAD and bisulfite treatment, we characterized patterns of cytosine methylation in two species of deer mouse (Peromyscus spp.) collected in the same region in Michigan in 1940, 2003, and 2013-2016. We successfully estimated methylation in specimens of all age groups, though older specimens yielded less data and showed greater interindividual variation in data yield than newer specimens. Global methylation estimates were reduced in the oldest specimens (76 years old) relative to the newest specimens (1-3 years old), which may reflect post mortem hydrolytic deamination. Methylation was reduced in promoter regions relative to gene bodies and showed greater bimodality in autosomes relative to female X chromosomes, consistent with expectations for methylation in mammalian somatic cells. Our work demonstrates the utility of historic specimens for methylation analyses, as with genomic analyses; however, studies will need to accommodate the large variance in the quantity of data produced by older specimens.]]>
Wed, 31 Dec 1969 19:00:00 EST
Understanding osteoarthritis pathogenesis: a multiomics system-based approach. Ratneswaran A, Rockel JS, Kapoor M
Curr Opin Rheumatol (Nov 2019)

Osteoarthritis is a heterogenous, multifactorial condition regulated by complex biological interactions at multiple levels. Comprehensive understanding of these regulatory interactions is required to develop feasible advances to improve patient outcomes. Improvements in technology have made extensive genomic, transcriptomic, epigenomic, proteomic, and metabolomic profiling possible. This review summarizes findings over the past 20 months related to omics technologies in osteoarthritis and examines how using a multiomics approach is necessary for advancing our understanding of osteoarthritis as a disease to improve precision osteoarthritis treatments.]]>
Wed, 31 Dec 1969 19:00:00 EST
Potential of Melatonin as Adjuvant Therapy of Oral Cancer in the Era of Epigenomics. Capote-Moreno A, Ramos E, Egea J, López-Muñoz F, Gil-Martín E, Romero A
Cancers (Basel) (Nov 2019)

The wide variety of epigenetic controls available is rapidly expanding the knowledge of molecular biology even overflowing it. At the same time, it can illuminate unsuspected ways of understanding the etiology of cancer. New emerging therapeutic horizons, then, promise to overcome the current antitumor strategies need. The translational utility of this complexity is particularly welcome in oral cancer (OC), in which natural history is alarmingly disappointing due to the invasive and mutilating surgery, the high relapsing rate, the poor quality of life and the reduced survival after diagnosis. Melatonin activates protective receptor-dependent and receptor-independent processes that prevent tissue cancerisation and inhibit progressive tumor malignancy and metastasis. Related evidence has shown that melatonin pleiotropy encompasses gene expression regulation through all the three best-characterized epigenetic mechanisms: DNA methylation, chromatin modification, and non-coding RNA. OC has received less attention than other cancers despite prognosis is usually negative and there are no significant therapy improvements recorded in the past decade. However, a large research effort is being carried out to elucidate how melatonin´s machinery can prevent epigenetic insults that lead to cancer. In the light of recent findings, a comprehensive examination of biochemistry through which melatonin may reverse epigenetic aberrations in OC is an extraordinary opportunity to take a step forward in the clinical management of patients.]]>
Wed, 31 Dec 1969 19:00:00 EST