'; ?> 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 Wed, 08 Dec 2021 02:07:33 EST Wed, 08 Dec 2021 02:07:33 EST jirtle@radonc.duke.edu james001@jirtle.com Impact of medical imaging on the epigenome - low-dose exposure in the course of computed tomography does not induce detectable changes of DNA-methylation profiles in peripheral blood cells. Becker BV, Kaatsch HL, Nestler K, Jakobi J, Schäfer B, Hantke T, Brockmann MA, Waldeck S, Port M, Ullmann R
Int J Radiat Biol (Dec 2021)

Computed tomography (CT) is a main contributor to artificial low-dose exposure. Understanding the biological effects induced by CT exposure and their dependency on the characteristics of photon spectra is essential for knowledge-driven risk assessment. In a previous gene expression study, we have identified upregulation of , , , and after ex vivo exposure with single-energy CT and dual-energy CT (DECT). In this study, we focused on CT-induced changes of DNA methylation. This epigenetic modification of DNA is a central regulator of gene expression and instrumental in preserving genome integrity. Previous studies reported focal hypermethylation and global hypomethylation after exposure with doses above 100 mSv, however, the effect of low dose exposure on DNA methylation is hardly explored.]]> Wed, 31 Dec 1969 19:00:00 EST Context-dependent transcriptional regulation of microglial proliferation. Belhocine S, Machado Xavier A, Distéfano-Gagné F, Fiola S, Rivest S, Gosselin D
Glia (Dec 2021)

Microglia proliferate during brain development and brain lesions, but how this is coordinated at the transcriptional level is not well understood. Here, we investigated fundamental aspects of the transcriptional process associated with proliferation of mouse microglia during postnatal development and in adults in a model of induced microglial depletion-repopulation. While each proliferative subset displayed globally a distinct signature of gene expression, they also co-expressed a subgroup of 1370 genes at higher levels than quiescent microglia. Expression of these may be coordinated by one of two mechanisms of regulation with distinct properties. A first mechanism augments expression of genes already expressed in quiescent microglia and is subject to regulation by Klf/Sp, Nfy, and Ets transcription factors. Alternatively, a second mechanism enables de novo transcription of cell cycle genes and requires additional regulatory input from Lin54 and E2f transcription factors. Of note, transcriptional upregulation of E2f1 and E2f2 family members may represent a critical regulatory checkpoint to enable microglia to achieve efficient cell cycling. Furthermore, analysis of the activity profile of the repertoire of promoter-distal genomic regulatory elements suggests a relatively restricted role for these elements in coordinating cell cycle gene expression in microglia. Overall, proliferating microglia integrates regulation of cell cycle gene expression with their broader, context-dependent, transcriptional landscape.]]> Wed, 31 Dec 1969 19:00:00 EST Genome-wide Signatures of Early-Life Stress: Influence of Sex. Parel ST, Peña CJ
Biol Psychiatry (Jan 2022)

Both history of early-life stress (ELS) and female sex are associated with increased risk for depression. The complexity of how ELS interacts with brain development and sex to impart risk for multifaceted neuropsychiatric disorders is also unlikely to be understood by examining changes in single genes. Here, we review an emerging literature on genome-wide transcriptional and epigenetic signatures of ELS and the potential moderating influence of sex. We discuss evidence both that there are latent sex differences revealed by ELS and that ELS itself produces latent transcriptomic changes revealed by adult stress. In instances where there are broad similarities in global signatures of ELS among females and males, genes that contribute to these patterns are largely distinct based on sex. As this area of investigation grows, an effort should be made to better understand the sex-specific impact of ELS within the human brain, specific contributions of chromosomal versus hormonal sex, how ELS alters the time course of normal transcriptional development, and the cell-type specificity of transcriptomic and epigenomic changes in the brain. A better understanding of how ELS interacts with sex to alter transcriptomic and epigenomic signatures in the brain will inform individualized therapeutic strategies to prevent or ameliorate depression and other psychiatric disorders in this vulnerable population.]]> Wed, 31 Dec 1969 19:00:00 EST Recent advances in single-cell epigenomics. Harada A, Kimura H, Ohkawa Y
Curr Opin Struct Biol (Dec 2021)

The analysis of gene expression regulation, or the epigenome analysis, at the single-cell level is at the forefront of genomics research. To elucidate the mechanisms that regulate gene expression, chromatin immunoprecipitation has been conventionally used for determining the binding sites of DNA-binding proteins, such as histones and transcription factors. Now several new approaches have been emerged to reveal epigenome states at the single-cell level. Instead of using immunoprecipitation of fragmented chromatin, in situ reactions using cells or nuclei, combining with transposase tagging and other methods, have enabled single-cell analysis. Furthermore, single-cell multiomics techniques to simultaneously profiling transcriptome and open chromatin or histone modification have been developed. These single-cell analyses have the potential to identify different cell types in a cell population and reveal the dynamic changes of gene regulation, although those technologies have not yet reached a level for general application.]]> Wed, 31 Dec 1969 19:00:00 EST Self-functional gold nanoprobes for intra-nuclear epigenomic monitoring of cancer stem-like cells. Verma AH, Ganesh S, Venkatakrishnan K, Tan B
Biosens Bioelectron (Jan 2022)

Cancer epigenomic-environment is a core center of a tumor's genetic and epigenetic configuration. Surveying epigenomic-environment of cancer stem-like cells (CSC) is vital for developing novel diagnostic methods and improving current therapies since CSCs are among the most challenging clinical hurdles. To date, there exists no technique which can successfully monitor the epigenomics of CSC. Here, we have developed unique sub-10 nm Self-functional Gold Nanoprobes (GNP) as a CSC epigenomic monitoring platform that can easily maneuver into the nucleus while not producing any conformal changes to the genomic DNA. The GNP was synthesized using physical synthesis method of pulsed laser multiphoton ionization, which enabled the shrinking of GNP to 2.69 nm which helped us achieve two critical parameters for epigenomics monitoring: efficient nuclear uptake (98%) without complex functionalization and no conformational nuclear changes. The GNP efficiently generated SERS for structural, functional, molecular epigenetics, and nuclear proteomics in preclinical models of breast and lung CSCs. To the best of knowledge, this study is first to utilize the intranuclear epigenomic signal to distinguish between CSC from different tissues with >99% accuracy and specificity. Our findings are anticipated to help advance real-time epigenomics surveillance technologies such as nucleus-targeted drug surveillance and epigenomic prognosis and diagnostics.]]> Wed, 31 Dec 1969 19:00:00 EST The ups and downs of DNA methylation: an interview with Gerd Pfeifer. Pfeifer GP
Epigenomics (Dec 2021)

In this interview, Professor Gerd Pfeifer speaks with Storm Johnson, Commissioning Editor for , on his work to date in the field of DNA methylation. Dr. Pfeifer received a PhD degree from the University of Frankfurt, Germany. After postdoctoral work, he became a faculty member at the Beckman Research Institute of the City of Hope (Duarte, CA) in 1991. He is currently a full professor at the Van Andel Institute in Grand Rapids, MI. Dr. Pfeifer has served on several NIH advisory committees and has published over 300 research papers. Dr. Pfeifer's research interests are cancer etiology, molecular carcinogenesis and epigenetics. His expertise is in cellular and molecular biology. His lab currently works on epigenetic mechanisms of gene regulation in cancer and other diseases.]]> Wed, 31 Dec 1969 19:00:00 EST Effects of glufosinate-ammonium on male reproductive health: Focus on epigenome and transcriptome in mouse sperm. Ma X, Wang B, Li Z, Ding X, Wen Y, Shan W, Hu W, Wang X, Xia Y
Chemosphere (Jan 2022)

Glufosinate-ammonium (GLA) is a widely used herbicide with emerging concern over its neural and reproductive toxicity. To uncover potential effects of GLA on male reproductive health in mammals, adult male C57BL/6J mice were administered 0.2 mg/kg·d GLA for 5 weeks. After examination on fertility, testis histology and semen quality in the GLA group, we performed deep sequencing to identify repressive epigenetic marks including DNA methylation and histone modifications (H3K27me3 and H3K9me3), together with mRNA transcript levels in sperm. Then, we integrated multi-omics sequencing data to comprehensively explore GLA-induced epigenetic and transcriptomic alterations. We found no significant difference either on fertility, testis histology or semen quality-related indicators. As for epigenome, the protein level of H3K27me3 was significantly increased in GLA sperm. Next generation sequencing showed alterations of these epigenetic marks and extensive transcription inhibition in sperm. These differential repressive marks were mainly distributed at intergenic regions and introns. According to results by Gene Ontology enrichment analysis, both differentially methylated and expressed genes were mainly enriched in pathways related to synapse organization. Subtle differences in genomic imprinting were also observed between the two groups. These results suggested that GLA predominantly impaired sperm epigenome and transcriptome in mice, with little effect on fertility, testis histology or semen quality. Further studies on human sperm using similar strategies need to be conducted for a better understanding of the male reproductive toxicity of GLA.]]> Wed, 31 Dec 1969 19:00:00 EST Machine Learning in Epigenomics: Insights into Cancer Biology and Medicine. Arslan E, Schulz J, Rai K
Biochim Biophys Acta Rev Cancer (12 2021)

The recent deluge of genome-wide technologies for the mapping of the epigenome and resulting data in cancer samples has provided the opportunity for gaining insights into and understanding the roles of epigenetic processes in cancer. However, the complexity, high-dimensionality, sparsity, and noise associated with these data pose challenges for extensive integrative analyses. Machine Learning (ML) algorithms are particularly suited for epigenomic data analyses due to their flexibility and ability to learn underlying hidden structures. We will discuss four overlapping but distinct major categories under ML: dimensionality reduction, unsupervised methods, supervised methods, and deep learning (DL). We review the preferred use cases of these algorithms in analyses of cancer epigenomics data with the hope to provide an overview of how ML approaches can be used to explore fundamental questions on the roles of epigenome in cancer biology and medicine.]]> Wed, 31 Dec 1969 19:00:00 EST Insights into the molecular landscape of osteoarthritis in human tissues. Katsoula G, Kreitmaier P, Zeggini E
Curr Opin Rheumatol (Jan 2022)

To provide an overview of recent developments in the field of osteoarthritis research with a focus on insights gleaned from the application of different -omic technologies.]]> Wed, 31 Dec 1969 19:00:00 EST Clinical Utility of Methylation-Specific Multiplex Ligation-Dependent Probe Amplification for the Diagnosis of Prader-Willi Syndrome and Angelman Syndrome. Kim B, Park Y, Cho SI, Kim MJ, Chae JH, Kim JY, Seong MW, Park SS
Ann Lab Med (Jan 2022)

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are genomic imprinting disorders that are mainly caused by a deletion on 15q11-q13, the uniparental disomy of chromosome 15, or an imprinting defect. We evaluated the utility of methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as a diagnostic tool and for demonstrating the relationship between molecular mechanisms and clinical presentation.]]> Wed, 31 Dec 1969 19:00:00 EST Integrating SNPs-based genetic risk factor with blood epigenomic response of differentially arsenic-exposed rural subjects reveals disease-associated signaling pathways. Rehman MYA, Briedé JJ, van Herwijnen M, Krauskopf J, Jennen DGJ, Malik RN, Kleinjans JCS
Environ Pollut (Jan 2022)

Arsenic (As) contamination in groundwater is responsible for numerous adverse health outcomes among millions of people. Epigenetic alterations are among the most widely studied mechanisms of As toxicity. To understand how As exposure alters gene expression through epigenetic modifications, a systematic genome-wide study was designed to address the impact of multiple important single nucleotide polymorphisms (SNPs) related to As exposure on the methylome of drinking water As-exposed rural subjects from Pakistan. Urinary As levels were used to stratify subjects into low, medium and high exposure groups. Genome-wide DNA methylation was investigated using MeDIP in combination with NimbleGen 2.1 M Deluxe Promotor arrays. Transcriptome levels were measured using Agilent 8 × 60 K expression arrays. Genotyping of selected SNPs (As3MT, DNMT1a, ERCC2, EGFR and MTHFR) was measured and an integrated genetic risk factor for each respondent was calculated by assigning a specific value to the measured genotypes based on known risk allele numbers. To select a representative model related to As exposure we compared 9 linear mixed models comprising of model 1 (including the genetic risk factor), model 2 (without the genetic risk factor) and models with individual SNPs incorporated into the methylome data. Pathway analysis was performed using ConsensusPathDB. Model 1 comprising the integrated genetic risk factor disclosed biochemical pathways including muscle contraction, cardio-vascular diseases, ATR signaling, GPCR signaling, methionine metabolism and chromatin modification in association with hypo- and hyper-methylated gene targets. A unique pathway (direct P53 effector) was found associated with the individual DNMT1a polymorphism due to hyper-methylation of CSE1L and TRRAP. Most importantly, we provide here the first evidence of As-associated DNA methylation in relation with gene expression of ATR, ATF7IP, TPM3, UBE2J2. We report the first evidence that integrating SNPs data with methylome data generates a more representative epigenome profile and discloses a better insight in disease risks of As-exposed individuals.]]> Wed, 31 Dec 1969 19:00:00 EST How a cell decides its own fate: a single-cell view of molecular mechanisms and dynamics of cell-type specification. Mircea M, Semrau S
Biochem Soc Trans (Dec 2021)

On its path from a fertilized egg to one of the many cell types in a multicellular organism, a cell turns the blank canvas of its early embryonic state into a molecular profile fine-tuned to achieve a vital organismal function. This remarkable transformation emerges from the interplay between dynamically changing external signals, the cell's internal, variable state, and tremendously complex molecular machinery; we are only beginning to understand. Recently developed single-cell omics techniques have started to provide an unprecedented, comprehensive view of the molecular changes during cell-type specification and promise to reveal the underlying gene regulatory mechanism. The exponentially increasing amount of quantitative molecular data being created at the moment is slated to inform predictive, mathematical models. Such models can suggest novel ways to manipulate cell types experimentally, which has important biomedical applications. This review is meant to give the reader a starting point to participate in this exciting phase of molecular developmental biology. We first introduce some of the principal molecular players involved in cell-type specification and discuss the important organizing ability of biomolecular condensates, which has been discovered recently. We then review some of the most important single-cell omics methods and relevant findings they produced. We devote special attention to the dynamics of the molecular changes and discuss methods to measure them, most importantly lineage tracing. Finally, we introduce a conceptual framework that connects all molecular agents in a mathematical model and helps us make sense of the experimental data.]]> Wed, 31 Dec 1969 19:00:00 EST Potential roles of imprinted genes in the teratogenic effects of alcohol on the placenta, somatic growth, and the developing brain. Gutherz OR, Deyssenroth M, Li Q, Hao K, Jacobson JL, Chen J, Jacobson SW, Carter RC
Exp Neurol (Jan 2022)

Despite several decades of research and prevention efforts, fetal alcohol spectrum disorders (FASD) remain the most common preventable cause of neurodevelopmental disabilities worldwide. Animal and human studies have implicated fetal alcohol-induced alterations in epigenetic programming as a chief mechanism in FASD. Several studies have demonstrated fetal alcohol-related alterations in methylation and expression of imprinted genes in placental, brain, and embryonic tissue. Imprinted genes are epigenetically regulated in a parent-of-origin-specific manner, in which only the maternal or paternal allele is expressed, and the other allele is silenced. The chief functions of imprinted genes are in placental development, somatic growth, and neurobehavior-three domains characteristically affected in FASD. In this review, we summarize the growing body of literature characterizing prenatal alcohol-related alterations in imprinted gene methylation and/or expression and discuss potential mechanistic roles for these alterations in the teratogenic effects of prenatal alcohol exposure. Future research is needed to examine potential physiologic mechanisms by which alterations in imprinted genes disrupt development in FASD, which may, in turn, elucidate novel targets for intervention. Furthermore, mechanistic alterations in imprinted gene expression and/or methylation in FASD may inform screening assays that identify individuals with FASD neurobehavioral deficits who may benefit from early interventions.]]> Wed, 31 Dec 1969 19:00:00 EST Unsupervised learning of cross-modal mappings in multi-omics data for survival stratification of gastric cancer. Xu J, Xu B, Li Y, Su Z, Yao Y
Future Oncol (Dec 2021)

This study presents a survival stratification model based on multi-omics integration using bidirectional deep neural networks (BiDNNs) in gastric cancer. Based on the survival-related representation features yielded by BiDNNs through integrating transcriptomics and epigenomics data, K-means clustering analysis was performed to cluster tumor samples into different survival subgroups. The BiDNNs-based model was validated using tenfold cross-validation and in two independent confirmation cohorts. Using the BiDNNs-based survival stratification model, patients were grouped into two survival subgroups with log-rank p-value = 9.05E-05. The subgroups classification was robustly validated in tenfold cross-validation (C-index = 0.65 ± 0.02) and in two confirmation cohorts (E-GEOD-26253, C-index = 0.609; E-GEOD-62254, C-index = 0.706). We propose and validate a robust and stable BiDNN-based survival stratification model in gastric cancer.]]> Wed, 31 Dec 1969 19:00:00 EST Polymer Modeling of 3D Epigenome Folding: Application to Drosophila. Jost D
Methods Mol Biol (2022)

Mechanistic modeling in biology allows to investigate, based on first principles, if putative hypotheses are compatible with observations and to drive further experimental works. Along this line, polymer modeling has been instrumental in 3D genomics to better understand the impact of key mechanisms on the spatial genome organization. Here, I describe how polymer-based models can be practically used to study the role of epigenome in chromosome folding. I illustrate this methodology in the context of Drosophila epigenome folding.]]> Wed, 31 Dec 1969 19:00:00 EST Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature. Teruel M, Barturen G, Martínez-Bueno M, Castellini-Pérez O, Barroso-Gil M, Povedano E, Kerick M, Català-Moll F, Makowska Z, Buttgereit A,  ,  , Pers JO, Marañón C, Ballestar E, Martin J, Carnero-Montoro E, Alarcón-Riquelme ME
Sci Rep (Dec 2021)

Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population.]]> Wed, 31 Dec 1969 19:00:00 EST Visualizing and Annotating Hi-C Data. Pal K, Ferrari F
Methods Mol Biol (2022)

Epigenomics studies require the combined analysis and integration of multiple types of data and annotations to extract biologically relevant information. In this context, sophisticated data visualization techniques are fundamental to identify meaningful patterns in the data in relation to the genomic coordinates. Data visualization for Hi-C contact matrices is even more complex as each data point represents the interaction between two distant genomic loci and their three-dimensional positioning must be considered. In this chapter we illustrate how to obtain sophisticated plots showing Hi-C data along with annotations for other genomic features and epigenomics data. For the example code used in this chapter we rely on a Bioconductor package able to handle even high-resolution Hi-C datasets. The provided examples are explained in details and highly customizable, thus facilitating their extension and adoption by end users for other studies.]]> Wed, 31 Dec 1969 19:00:00 EST Role of miRNAs as biomarkers of COVID-19: a scoping review of the status and future directions for research in this field. Visacri MB, Nicoletti AS, Pincinato EC, Loren P, Saavedra N, Saavedra K, Salazar LA, Moriel P
Biomark Med (12 2021)

miRNAs are potential biomarkers of several diseases. This review aimed to identify the miRNAs that could serve as biomarkers of COVID-19. A literature search of nine databases was carried out for studies published before 13 June 2021 that described dysregulated miRNAs in cells or animals infected by SARS-CoV-2 or in patients with COVID-19. Two independent reviewers selected the studies and extracted data; disagreements were resolved by a third reviewer. Twenty studies were included in this scoping review; results suggested that miR-21-5p, miR-146a, miR-126-3p, miR-144 and miR-155 are the most important dysregulated miRNAs that could serve as biomarkers for diagnosing and indicating the severity of COVID-19. miRNAs appear to play key roles in viral replication, proliferation of infected cells, immune response, inflammation and cardiovascular dysfunction. This review provides insights into the role of miRNAs as biomarkers in COVID-19 and the current status and future directions for research in this field.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic modifications potentially controlling the allelic expression of imprinted genes in sunflower endosperm. Zhang Z, Yu S, Li J, Zhu Y, Jiang S, Xia H, Zhou Y, Sun D, Liu M, Li C, Zhu Y, Ruan Y, Dong X
BMC Plant Biol (Dec 2021)

Genomic imprinting is an epigenetic phenomenon mainly occurs in endosperm of flowering plants. Genome-wide identification of imprinted genes have been completed in several dicot Cruciferous plant and monocot crops.]]> Wed, 31 Dec 1969 19:00:00 EST Derivation and investigation of the first human cell-based model of Beckwith-Wiedemann syndrome. Chang S, Hur SK, Naveh NSS, Thorvaldsen JL, French DL, Gagne AL, Jobaliya CD, Anguera MC, Bartolomei MS, Kalish JM
Epigenetics (Dec 2021)

Genomic imprinting is a rare form of gene expression in mammals in which a small number of genes are expressed in a parent-of-origin-specific manner. The aetiology of human imprinting disorders is diverse and includes chromosomal abnormalities, mutations, and epigenetic dysregulation of imprinted genes. The most common human imprinting disorder is Beckwith-Wiedemann syndrome (BWS), frequently caused by uniparental isodisomy and DNA methylation alterations. Because these lesions cannot be easily engineered, induced pluripotent stem cells (iPSC) are a compelling alternative. Here, we describe the first iPSC model derived from patients with BWS. Due to the mosaic nature of BWS patients, both BWS and non-BWS iPSC lines were derived from the same patient's fibroblasts. Importantly, we determine that DNA methylation and gene expression patterns of the imprinted region in the iPSC lines reflect the parental cells and are stable over time. Additionally, we demonstrate that differential expression in insulin signalling, cell proliferation, and cell cycle pathways was seen in hepatocyte lineages derived from BWS lines compared to controls. Thus, this cell based-model can be used to investigate the role of imprinting in the pathogenesis of BWS in disease-relevant cell types.]]> Wed, 31 Dec 1969 19:00:00 EST