'; ?> 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, 24 Feb 2018 22:58:49 PST Sat, 24 Feb 2018 22:58:49 PST jirtle@radonc.duke.edu james001@jirtle.com Longitudinal analysis strategies for modelling epigenetic trajectories. Staley JR, Suderman M, Simpkin AJ, Gaunt TR, Heron J, Relton CL, Tilling K
Int J Epidemiol (Feb 2018)

DNA methylation levels are known to vary over time, and modelling these trajectories is crucial for our understanding of the biological relevance of these changes over time. However, due to the computational cost of fitting multilevel models across the epigenome, most trajectory modelling efforts to date have focused on a subset of CpG sites identified through epigenome-wide association studies (EWAS) at individual time-points.]]>
Wed, 31 Dec 1969 16:00:00 PST
Epigenetic effects of metformin: from molecular mechanisms to clinical implications. Bridgeman SC, Ellison GC, Melton PE, Newsholme P, Mamotte C
Diabetes Obes Metab (Feb 2018)

There is a growing body of evidence that links epigenetic modifications to type 2 diabetes. Researchers have more recently investigated effects of commonly used medications, including those prescribed for diabetes, on epigenetic processes. This work reviews the influence of the widely used antidiabetic drug metformin on epigenomics, microRNA levels and subsequent gene expression and potential clinical implications. Metformin may influence the activity of numerous epigenetic modifying enzymes, mostly via modulating the activation of AMP-activated protein kinase (AMPK). Activated AMPK can phosphorylate numerous substrates, including epigenetic enzymes such as histone acetyltransferases (HATs), class II histone deacetylases (HDACs) and DNA methyltransferases (DNMTs), generally resulting in their inhibition, although HAT1 activity may be increased. Metformin has also been reported to decrease expression of multiple histone methyltransferases, increase the activity of the class III HDAC SIRT1 and to decrease the influence of DNMT inhibitors. There is evidence that these alterations influence the epigenome and gene expression, and may contribute to the antidiabetic properties of metformin and potentially protect against cancer, cardiovascular disease, cognitive decline and aging. The expression levels of numerous microRNAs are also reportedly influenced by metformin treatment and may confer antidiabetic and anticancer activities. However, as the reported effects of metformin on epigenetic enzymes act to both increase and decrease histone acetylation, histone and DNA methylation, and gene expression, a significant degree of uncertainty exists on the overall effect of metformin on the epigenome, gene expression and subsequent effect on the health of metformin users.]]>
Wed, 31 Dec 1969 16:00:00 PST
Parent-of-origin-environment interactions in case-parent triads with or without independent controls. Gjerdevik M, Haaland Ã˜A, Romanowska J, Lie RT, Jugessur A, Gjessing HK
Ann Hum Genet (Mar 2018)

With case-parent triad data, one can frequently deduce parent of origin of the child's alleles. This allows a parent-of-origin (PoO) effect to be estimated as the ratio of relative risks associated with the alleles inherited from the mother and the father, respectively. A possible cause of PoO effects is DNA methylation, leading to genomic imprinting. Because environmental exposures may influence methylation patterns, gene-environment interaction studies should be extended to allow for interactions between PoO effects and environmental exposures (i.e., PoOxE). One should thus search for loci where the environmental exposure modifies the PoO effect. We have developed an extensive framework to analyze PoOxE effects in genome-wide association studies (GWAS), based on complete or incomplete case-parent triads with or without independent control triads. The interaction approach is based on analyzing triads in each exposure stratum using maximum likelihood estimation in a log-linear model. Interactions are then tested applying a Wald-based posttest of parameters across strata. Our framework includes a complete setup for power calculations. We have implemented the models in the R software package Haplin. To illustrate our PoOxE test, we applied the new methodology to top hits from our previous GWAS, assessing whether smoking during the periconceptional period modifies PoO effects on cleft palate only.]]>
Wed, 31 Dec 1969 16:00:00 PST
Thinking BIG rheumatology: how to make functional genomics data work for you. Winter DR
Arthritis Res Ther (Feb 2018)

High-throughput sequencing assays have become an increasingly common part of biological research across multiple fields. Even as the resulting sequences pile up in public databases, it is not always obvious how to make use of these data sets. Functional genomics offers approaches to integrate these "big" data into our understanding of rheumatic diseases. This review aims to provide a primer on thinking about big data from functional genomics in the context of rheumatology, using examples from the field's literature as well as the author's own work to illustrate the execution of functional genomics research. Study design is crucial to ensure the right samples are used to address the question of interest. In addition, sequencing assays produce a variety of data types, from gene expression to 3D chromatin structure and single-cell technologies, that can be integrated into a model of the underlying gene regulatory networks. The best approach for this analysis uses the scientific process: bioinformatic methods should be used in an iterative, hypothesis-driven manner to uncover the disease mechanism. Finally, the future of functional genomics will see big data fully integrated into rheumatology, leading to computationally trained researchers and interactive databases. The goal of this review is not to provide a manual, but to enhance the familiarity of readers with functional genomic approaches and provide a better sense of the challenges and possibilities.]]>
Wed, 31 Dec 1969 16:00:00 PST
DNA Methylation and Age-Independent Cardiovascular Risk, an Epigenome-Wide Approach: The REGICOR Study (REgistre GIroní del COR). Fernández-Sanlés A, Sayols-Baixeras S, Curcio S, Subirana I, Marrugat J, Elosua R
Arterioscler Thromb Vasc Biol (Mar 2018)

The objectives of this study were to decipher whether age-independent cardiovascular risk is associated with DNA methylation at 5'-cytosine-phosphate-guanine-3' (CpG) level and to determine whether these differential methylation signatures are associated with the incidence of cardiovascular events.]]>
Wed, 31 Dec 1969 16:00:00 PST
Plant Genetics and Molecular Biology: An Introduction. Varshney RK, Pandey MK, Chitikineni A
Adv Biochem Eng Biotechnol (Feb 2018)

The rapidly evolving technologies can serve as a potential growth engine in agriculture as many of these technologies have revolutionized several industries in the recent past. The tremendous advancements in biotechnology methods, cost-effective sequencing technology, refinement of genomic tools, and standardization of modern genomics-assisted breeding methods hold great promise in taking the global agriculture to the next level through development of improved climate-smart seeds. These technologies can dramatically increase our capacity to understand the molecular basis of traits and utilize the available resources for accelerated development of stable high-yielding, nutritious, input-use efficient, and climate-smart crop varieties. This book aimed to document the monumental advances witnessed during the last decade in multiple fields of plant biotechnology such as genetics, structural and functional genomics, trait and gene discovery, transcriptomics, proteomics, metabolomics, epigenomics, nanotechnology, and analytical tools. This book will serve to update the scientific community, academicians, and other stakeholders in global agriculture on the rapid progress in various areas of agricultural biotechnology. This chapter provides a summary of the book, "Plant Genetics and Molecular Biology." Graphical Abstract.]]>
Wed, 31 Dec 1969 16:00:00 PST
Perceived Racial Discrimination and DNA Methylation Among African American Women in the InterGEN Study. de Mendoza VB, Huang Y, Crusto CA, Sun YV, Taylor JY
Biol Res Nurs (Mar 2018)

Experiences of racial discrimination have been associated with poor health outcomes. Little is known, however, about how perceived racial discrimination influences DNA methylation (DNAm) among African Americans (AAs). We examined the association of experiences of discrimination with DNAm among AA women in the Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure (InterGEN) study.]]>
Wed, 31 Dec 1969 16:00:00 PST
DNA Methylation Dynamics of Genomic Imprinting in Mouse Development. SanMiguel JM, Bartolomei MS
Biol Reprod (Feb 2018)

DNA methylation is an essential epigenetic mark crucial for normal mammalian development. This modification controls the expression of a unique class of genes, designated as imprinted, which are expressed monoallelically and in a parent-of-origin-specific manner. Proper parental allele-specific DNA methylation at imprinting control regions (ICRs) is necessary for appropriate imprinting. Processes that deregulate DNA methylation of imprinted loci cause disease in humans. DNA methylation patterns dramatically change during mammalian development: first, the majority of the genome, with the exception of ICRs, is demethylated after fertilization, and subsequently undergoes genome-wide de novo DNA methylation. Secondly, after primordial germ cells are specified in the embryo, another wave of demethylation occurs, with ICR demethylation occurring late in the process. Lastly, ICRs reacquire DNA methylation imprints in developing germ cells. We describe the past discoveries and current literature defining these crucial dynamics in relation to imprinted genes and the rest of the genome.]]>
Wed, 31 Dec 1969 16:00:00 PST
Roadmap for investigating epigenome deregulation and environmental origins of cancer. Herceg Z, Ghantous A, Wild CP, Sklias A, Casati L, Duthie SJ, Fry R, Issa JP, Kellermayer R, Koturbash I, Kondo Y, Lepeule J, Lima SCS, Marsit CJ, Rakyan V, Saffery R, Taylor JA, Teschendorff AE, Ushijima T, Vineis P, Walker CL, Waterland RA, Wiemels J, Ambatipudi S, Degli Esposti D, Hernandez-Vargas H
Int J Cancer (Mar 2018)

The interaction between the (epi)genetic makeup of an individual and his/her environmental exposure record (exposome) is accepted as a determinant factor for a significant proportion of human malignancies. Recent evidence has highlighted the key role of epigenetic mechanisms in mediating gene-environment interactions and translating exposures into tumorigenesis. There is also growing evidence that epigenetic changes may be risk factor-specific ("fingerprints") that should prove instrumental in the discovery of new biomarkers in cancer. Here, we review the state of the science of epigenetics associated with environmental stimuli and cancer risk, highlighting key developments in the field. Critical knowledge gaps and research needs are discussed and advances in epigenomics that may help in understanding the functional relevance of epigenetic alterations. Key elements required for causality inferences linking epigenetic changes to exposure and cancer are discussed and how these alterations can be incorporated in carcinogen evaluation and in understanding mechanisms underlying epigenome deregulation by the environment.]]>
Wed, 31 Dec 1969 16:00:00 PST
Classification of heterogeneous genetic variations of microRNA regulome in cancer. Hrovatin K, Kunej T
Cancer Lett (Apr 2018)

Genetic variations and differential expression of miRNA regulome components are associated with cancer. Thus miRNA based diagnosis and treatments have been proposed. However, to better explore these options, the molecular changes in miRNA regulome must be understood. MicroRNAs can be involved in regulation of oncogenes and tumour suppressors. As each miRNA targets broad range of genes, minor changes in miRNAs can have great effects, contributing to cell transformation. Many genetic variants of miRNA regulome have been reported to be associated with cancer, but this information needs to be systematized. Therefore, we here classify different types of genetic variations of miRNA regulome in cancer. Genetic variations are comprised of structural and short polymorphisms and changes in epigenetic landscape. Additionally, unexplained differential expression is often reported. These alterations affect miRNA genes and their regulatory elements, processing machinery, degradation machinery, and targets, leading to changes in miRNA silencing. However, miRNA regulome components are not equally explored. A systematic overview over miRNA regulome can contribute to more targeted study design and understanding of miRNA function. We also present treatments and diagnosis based on miRNA regulome genetic variability and expression.]]>
Wed, 31 Dec 1969 16:00:00 PST
Biological function and histone recognition of family IV bromodomain-containing proteins. Lloyd JT, Glass KC
J Cell Physiol (Mar 2018)

Bromodomain proteins function as epigenetic readers that recognize acetylated histone tails to facilitate the transcription of target genes. There are approximately 60 known human bromodomains, which are divided into eight sub-families based on structural conservation. The bromodomain-containing proteins in family IV include seven members (BRPF1, BRPF2, BRPF3, BRD7, BRD9, ATAD2, and ATAD2b). The bromodomains of each of these proteins recognize and bind acetyllysine residues on histone tails protruding from the nucleosome. However, the histone marks recognized by each bromodomain protein can be very different. The BRPF1 subunit of the MOZ histone acetyltransferase (HAT) recognizes acetylated histones H2AK5ac, H4K12ac, H3K14ac, H4K8ac, and H4K5ac. While the bromodomain of BRD7, a member of the SWI/SNF complex, was shown to preferentially recognize acetylated histones H3K9ac, H3K14ac, H4K8ac, H4K12ac, and H4K16ac. The bromodomains of BRPF2 and BRPF3 have similar sequences, and function as part of the HBO1 HAT complex, but there is limited data on which histone ligands they bind. Similarly, there is little known about the histone targets of the BRD9 and ATAD2b bromodomain proteins. Interestingly, the ATAD2 bromodomain was recently shown to preferentially bind to the di-acetylated H4K5acK12ac mark found in newly synthesized histones following DNA replication. However, despite the physiological importance of the family IV bromodomains, little is known about how they function at the molecular or atomic level. In this review, we summarize our understanding of how family IV bromodomains recognize and select for acetyllysine marks and discuss the importance of acetylated histone recognition for their biological functions.]]>
Wed, 31 Dec 1969 16:00:00 PST
Evolutionary analysis indicates that DNA alkylation damage is a byproduct of cytosine DNA methyltransferase activity. RoÅ¡ić S, Amouroux R, Requena CE, Gomes A, Emperle M, Beltran T, Rane JK, Linnett S, Selkirk ME, Schiffer PH, Bancroft AJ, Grencis RK, Jeltsch A, Hajkova P, Sarkies P
Nat Genet (Feb 2018)

Methylation at the 5 position of cytosine in DNA (5meC) is a key epigenetic mark in eukaryotes. Once introduced, 5meC can be maintained through DNA replication by the activity of 'maintenance' DNA methyltransferases (DNMTs). Despite their ancient origin, DNA methylation pathways differ widely across animals, such that 5meC is either confined to transcribed genes or lost altogether in several lineages. We used comparative epigenomics to investigate the evolution of DNA methylation. Although the model nematode Caenorhabditis elegans lacks DNA methylation, more basal nematodes retain cytosine DNA methylation, which is targeted to repeat loci. We found that DNA methylation coevolved with the DNA alkylation repair enzyme ALKB2 across eukaryotes. In addition, we found that DNMTs introduced the toxic lesion 3-methylcytosine into DNA both in vitro and in vivo. Alkylation damage is therefore intrinsically associated with DNMT activity, and this may promote the loss of DNA methylation in many species.]]>
Wed, 31 Dec 1969 16:00:00 PST
CRISPR and personalized Treg therapy: new insights into the treatment of rheumatoid arthritis. Safari F, Farajnia S, Arya M, Zarredar H, Nasrolahi A
Immunopharmacol Immunotoxicol (Feb 2018)

Rheumatoid arthritis (RA), as one of the most disabling autoimmune diseases, is a common health problem that progressively reduces the life quality of patients. Although various biologics have been introduced for RA, attempts to establish an efficient long-term therapies failed due to the heterogeneity of this disease.]]>
Wed, 31 Dec 1969 16:00:00 PST
Distinct methylation profile of mucinous ovarian carcinoma reveals susceptibility to proteasome inhibitors. Liew PL, Huang RL, Weng YC, Fang CL, Hui-Ming Huang T, Lai HC
Int J Cancer (Feb 2018)

Mucinous type of epithelial ovarian cancer (MuOC) is a unique subtype with a poor survival outcome in recurrent and advanced stages. The role of type-specific epigenomics and its clinical significance remain uncertain. We analyzed the methylomic profiles of six benign mucinous adenomas, 24 MuOCs, 103 serous type of epithelial ovarian cancers (SeOCs), and 337 nonepithelial ovarian cancers. MuOC and SeOC exhibited distinct DNA methylation profiles comprising 101 genes, 81 of which exhibited low methylation in MuOC and were associated with the response to glucocorticoid, ATP hydrolysis-coupled proton transport, proteolysis involved in the cellular protein catabolic process, and ion transmembrane transport. Hierarchical clustering analysis showed that the profiles of MuOC were similar to colorectal adenocarcinoma, and stomach adenocarcinoma. Genetic interaction network analysis of differentially methylated genes in MuOC showed a dominant network module is the proteasome subunit beta (PSMB) family. Combined functional module and methylation analysis identified PSMB8 as a candidate marker for MuOC. Immunohistochemical staining of PSMB8 used to validate in 94 samples of ovarian tumors (mucinous adenoma, MuOC, or SeOC) and 62 samples of gastrointestinal cancer. PSMB8 was commonly expressed in MuOC and gastrointestinal cancer samples, predominantly as strong cytoplasmic and occasionally weak nuclei staining, but was not expressed in SeOC samples. Carfilzomib, a second-generation proteasome inhibitor, suppressed MuOC cell growth in vitro. This study unveiled a mucinous-type-specific methylation profile and suggests the potential use of a proteasome inhibitor to treat MuOC. This article is protected by copyright. All rights reserved.]]>
Wed, 31 Dec 1969 16:00:00 PST
Molecular and clinical studies in eight patients with Temple syndrome. Gillessen-Kaesbach G, Albrecht B, Eggermann T, Elbracht M, Mitter D, Morlot S, van Ravenswaaij-Arts CMA, Schulz S, Strobl-Wildemann G, Buiting K, Beygo J
Clin Genet (Feb 2018)

Temple syndrome (TS14, #616222) is a rare imprinting disorder characterised by phenotypic features including pre- and postnatal growth retardation, muscular hypotonia and feeding difficulties in infancy, early puberty and short stature with small hands and feet and often truncal obesity. It is caused by maternal uniparental disomies, paternal deletions and primary imprinting defects that affect the chromosomal region 14q32 and lead to a disturbed expression of imprinted genes in this region. Here we present detailed clinical data of eight patients with Temple syndrome, four with an imprinting defect, two with an imprinting defect in a mosaic state as well as one complete and one segmental maternal uniparental disomy of chromosome 14.]]>
Wed, 31 Dec 1969 16:00:00 PST
Modified aging of elite athletes revealed by analysis of epigenetic age markers. Spólnicka M, Pośpiech E, Adamczyk JG, Freire-Aradas A, Pepłońska B, Zbieć-Piekarska R, Makowska Å», Pięta A, Lareu MV, Phillips C, Płoski R, Å»ekanowski C, Branicki W
Aging (Albany NY) (Feb 2018)

Recent progress in epigenomics has led to the development of prediction systems that enable accurate age estimation from DNA methylation data. Our objective was to track responses to intense physical exercise of individual age-correlated DNA methylation markers and to infer their potential impact on the aging processes. The study showed accelerated DNA hypermethylation for two CpG sites inand. Both markers predicted the investigated elite athletes to be several years older than controls and this effect was more substantial in subjects involved in power sports. Accordingly, the complete 5-CpG model revealed age acceleration of elite athletes (=1.503x10) and the result was more significant amongst power athletes (P=1.051x10). The modified methylation ofandin top athletes may be accounted for by the biological roles played by these genes. Their known anti-tumour and anti-inflammatory activities suggests that intense physical training has a complex influence on aging and potentially launches signalling networks that contribute to the observed lower risk of elite athletes to develop cardiovascular disease and cancer.]]>
Wed, 31 Dec 1969 16:00:00 PST
Positional effects revealed in Illumina methylation array and the impact on analysis. Jiao C, Zhang C, Dai R, Xia Y, Wang K, Giase G, Chen C, Liu C
Epigenomics (Feb 2018)

We aimed to prove the existence of positional effects in the Illumina methylation beadchip data and to find an optimal correction method.]]>
Wed, 31 Dec 1969 16:00:00 PST
Optimized methods of chromatin immunoprecipitation (ChIP) for profiling histone modifications in industrial microalgae Nannochloropsis spp. Wei L, Xu J
J Phycol (Feb 2018)

Epigenetic factors such as histone modifications play integral roles in plant development and stress response, yet their implications in algae remain poorly understood. In the industrial oleaginous microalgae Nannochloropsis spp., the lack of an efficient methodology for chromatin immunoprecipitation (ChIP), which determines the specific genomic location of various histone modifications, has hindered probing the epigenetic basis of their photosynthetic carbon conversion and storage as oil. Here, a detailed ChIP protocol was developed for Nannochloropsis oceanica, which represents a reliable approach for the analysis of histone modifications, chromatin state, and transcription factor binding sites at the epigenetic level. Using ChIP-qPCR, genes related to photosynthetic carbon fixation in this microalga were systematically assessed. Furthermore, a ChIP-Seq protocol was established and optimized, which generated a genome-wide profile of histone-modification events, using histone mark H3K9Ac as an example. These results are the first step for appreciation of the chromatin landscape in industrial oleaginous microalgae and for epigenetics-based microalgal feedstock development. This article is protected by copyright. All rights reserved.]]>
Wed, 31 Dec 1969 16:00:00 PST
Lineage-Determining Transcription Factor TCF-1 Initiates the Epigenetic Identity of T Cells. Johnson JL, Georgakilas G, Petrovic J, Kurachi M, Cai S, Harly C, Pear WS, Bhandoola A, Wherry EJ, Vahedi G
Immunity (Feb 2018)

T cell development is orchestrated by transcription factors that regulate the expression of genes initially buried within inaccessible chromatin, but the transcription factors that establish the regulatory landscape of the T cell lineage remain unknown. Profiling chromatin accessibility at eight stages of T cell development revealed the selective enrichment of TCF-1 at genomic regions that became accessible at the earliest stages of development. TCF-1 was further required for the accessibility of these regulatory elements and at the single-cell level, it dictated a coordinate opening of chromatin in T cells. TCF-1 expression in fibroblasts generated de novo chromatin accessibility even at chromatin regions with repressive marks, inducing the expression of T cell-restricted genes. These results indicate that a mechanism by which TCF-1 controls T cell fate is through its widespread ability to target silent chromatin and establish the epigenetic identity of T cells.]]>
Wed, 31 Dec 1969 16:00:00 PST
Hallmarks of cancer: The CRISPR generation. Moses C, Garcia-Bloj B, Harvey AR, Blancafort P
Eur J Cancer (Feb 2018)

The hallmarks of cancer were proposed as a logical framework to guide research efforts that aim to understand the molecular mechanisms and derive treatments for this highly complex disease. Recent technological advances, including comprehensive sequencing of different cancer subtypes, have illuminated how genetic and epigenetic alterations are associated with specific hallmarks of cancer. However, as these associations are purely descriptive, one particularly exciting development is the emergence of genome editing technologies, which enable rapid generation of precise genetic and epigenetic modifications to assess the consequences of these perturbations on the cancer phenotype. The most recently developed of these tools, the system of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), consists of an RNA-guided endonuclease that can be repurposed to edit both genome and epigenome with high specificity, and facilitates the functional interrogation of multiple loci in parallel. This system has the potential to dramatically accelerate progress in cancer research, whether by modelling the genesis and progression of cancer in vitro and in vivo, screening for novel therapeutic targets, conducting functional genomics/epigenomics, or generating targeted cancer therapies. Here, we discuss CRISPR research on each of the ten hallmarks of cancer, outline potential barriers for its clinical implementation and speculate on the advances it may allow in cancer research in the near future.]]>
Wed, 31 Dec 1969 16:00:00 PST