'; ?> 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, 15 Aug 2018 00:43:28 EDT Wed, 15 Aug 2018 00:43:28 EDT jirtle@radonc.duke.edu james001@jirtle.com Resveratrol Reverts Epigenetic and Transcription Changes Caused by Smoke Inhalation on Bone-Related Genes in Rats. Lameira AG, Françoso BG, Absy S, Pecorari VG, Casati MZ, Ribeiro FV, Andia DC
DNA Cell Biol (Aug 2018)

We investigated the effects of cigarette smoke (CS) and resveratrol intake on the modulation of bone repair-related genes through epigenetic mechanisms at the global and gene-specific levels, after 30 days of calvarial defects were created, in rats. The samples were assigned to three groups as follows: no CS, CS, and CS/resveratrol. After evaluation of global (5 hmC) changes and epigenetic and transcription regulation at gene-specific levels, CS group showed increased 5 hmC and Tets transcripts with demethylation at Rankl and Trap promoters (p ≤ 0.01), linked to their increased gene expression (p ≤ 0.001). These modifications were reverted in the CS/resveratrol group. Opposite patterns were observed among CS and CS/resveratrol for epigenetic enzyme transcripts with higher levels of Dnmts in the CS/resveratrol (p ≤ 0.01). No CS and CS/resveratrol demonstrated similar gene expression levels for all Tets and bone-related genes. Resveratrol reverts epigenetic and transcription changes caused by CS at both global and gene-specific levels in bone-related and epigenetic machinery genes, emphasizing the resveratrol as biological modulator for CS in rats.]]>
Wed, 31 Dec 1969 19:00:00 EST
Long noncoding RNAs: regulation, function and cancer. Rafiee A, Riazi-Rad F, Havaskary M, Nuri F
Biotechnol Genet Eng Rev (Aug 2018)

Long noncoding RNAs (lncRNAs) are non-protein-coding RNA transcripts that exert a key role in many cellular processes and have potential toward addressing disease etiology. Here, we review existing noncoding RNA classes and then describe a variety of mechanisms and functions by which lncRNAs regulate gene expression such as chromatin remodeling, genomic imprinting, gene transcription and post-transcriptional processing. We also examine several lncRNAs that contribute significantly to pathogenesis, oncogenesis, tumor suppression and cell cycle arrest of diverse cancer types and also give a summary of the pathways that lncRNAs might be involved in.]]>
Wed, 31 Dec 1969 19:00:00 EST
OBscure but not OBsolete: Perturbations of the frontal cortex in common between rodent olfactory bulbectomy model and major depression. Rajkumar R, Dawe GS
J Chem Neuroanat (Sep 2018)

Olfactory bulbectomy (OBX) has been used as a model of depression over several decades. This model presupposes a mechanism that is still not proven in clinical depression. A wealth of clinical literature has focused on the derangements in frontal cortex (prefrontal, orbitofrontal and anterior cingulate cortices) associated with depression. In this comprehensive review, anatomical, electrophysiological and molecular sequelae of bulbectomy in the rodent frontal cortex are explored and compared with findings on brains of humans with major depression. Certain commonalities in neurobiological features of the perturbed frontal cortex in the bulbectomised rodent and the depressed human brain are evident. Also, meta-analysis reports on clinical studies on depressed patients provide prima facie evidence that perturbations in the frontal cortex are associated with major depression. Analysing the pattern of perturbations in the chemical neuroanatomy of the frontal cortex will contribute to understanding of the neurobiology of depression. Revisiting the OBX model of depression to examine these neurobiological changes in frontal cortex with contemporary imaging, proteomics, lipidomics, metabolomics and epigenomics technologies is proposed as an approach to enhance the translational value of this animal model to facilitate identification of targets and biomarkers for clinical depression.]]>
Wed, 31 Dec 1969 19:00:00 EST
Placental Defects: An Epigenetic Perspective. Deshpande SS, Balasinor NH
Reprod Sci (08 2018)

Placenta, the first organ to be formed during gestation, plays a crucial role in intrauterine regulation of fetal growth and is involved in several functions during fetal development such as exchange of nutrients, wastes, and gases; protection against maternal immune rejection; and various metabolic and endocrine functions. Several studies have shown the regulation of epigenetic factors and the phenomenon of genomic imprinting in placentation and embryogenesis. Any gain or loss of imprint marks in the placenta has been shown to associate with severe placental defects which in turn affect both the mother and the growing fetus and can have long-term effects during adulthood. Using candidate and genome-wide high throughput approaches, several studies have shown association between aberrant epigenetic factors in the form of DNA methylation, histone modifications, and non-coding RNAs and placental defects in both human and animal models as well as using in vitro studies. In the current review, we discuss several placenta-related pathophysiologies and their association with various aberrant epigenetic factors and gene expression patterns in both in vivo and in vitro systems. This review will help the researchers gain insight into the recent evidences in the area of placentation and epigenetics and to design novel strategies to study and prevent the defects in this underestimated organ.]]>
Wed, 31 Dec 1969 19:00:00 EST
'Omic' technologies as a helpful tool in radioecological research. Volkova PY, Geras'kin SA
J Environ Radioact (Sep 2018)

This article presents a brief review of the modern 'omic' technologies, namely genomics, epigenomics, transcriptomics, proteomics, and metabolomics, as well as the examples of their possible use in radioecology. For each technology, a short description of advances, limitations, and instrumental applications is given. In addition, the review contains examples of successful use of 'omic' technologies in the assessment of biological effects of pollutants in the field conditions.]]>
Wed, 31 Dec 1969 19:00:00 EST
Environmental effects on chromatin repression at imprinted genes and endogenous retroviruses. Pathak R, Feil R
Curr Opin Chem Biol (Aug 2018)

Environmental factors can perturb epigenetic regulation. In mammals, most studies have focused on repressive DNA methylation. Two attractive model systems to monitor environmentally triggered drifts in DNA methylation are genomic imprinting and endogenous retroviruses (ERVs), particularly intracisternal-A particles (IAPs). These systems show mechanistic similarities in their repressive chromatin organization, which in somatic cells is comparable between the DNA-methylated alleles of imprinted differentially methylated regions (DMRs) and repressed ERVs. Here, we present how during development, nutrition and chemical components can perturb DNA methylation at imprinted genes and ERVs, and discuss the still poorly understood underlying mechanisms.]]>
Wed, 31 Dec 1969 19:00:00 EST
Genome-wide survey of parent-of-origin effects on DNA methylation identifies candidate imprinted loci in humans. Cuellar Partida G, Laurin C, Ring SM, Gaunt TR, McRae AF, Visscher PM, Montgomery GW, Martin NG, Hemani G, Suderman M, Relton CL, Davey Smith G, Evans DM
Hum Mol Genet (Aug 2018)

Genomic imprinting is an epigenetic mechanism leading to parent-of-origin silencing of alleles. So far, the precise number of imprinted regions in humans is uncertain. In this study, we leveraged genome-wide DNA methylation in whole blood measured longitudinally at three time points (birth, childhood and adolescence) and genome-wide association studies (GWAS) data in 740 mother-child duos from the Avon Longitudinal Study of parents and children to identify candidate imprinted loci. We reasoned that cis-meQTLs at genomic regions that were imprinted would show strong evidence of parent-of-origin associations with DNA methylation, enabling the detection of imprinted regions. Using this approach, we identified genome-wide significant cis-meQTLs that exhibited parent-of-origin effects (POEs) at 82 loci, 34 novel and 48 regions previously implicated in imprinting (3.7-10
Wed, 31 Dec 1969 19:00:00 EST
Fibrosis: Lessons from OMICS analyses of the human lung. Yu G, Ibarra GH, Kaminski N
Matrix Biol (Aug 2018)

In recent decades there has been a significant shift in our understanding of idiopathic pulmonary fibrosis (IPF), a progressive and lethal disorder. While initially much of the mechanistic understanding was derived from hypotheses generated from animal models of disease, in recent decades new insights derived from humans with IPF have taken precedence. This is mainly because of the establishment of large collections of IPF lung tissues and patient cohorts, and the emergence of high throughput profiling technologies collectively termed 'omics' technologies based on their shared suffix. In this review we describe impacts of 'omics' analyses of human IPF samples on our understanding of the disease. In particular, we discuss the results of genomics and transcriptomics studies, as well as proteomics, epigenomics and metabolomics. We then describe how these findings can be integrated in a modified paradigm of human idiopathic pulmonary fibrosis, that introduces the 'hallmarks of aging' as a central theme in the IPF lung. This allows resolution of all the disparate cellular and molecular features in IPF, from the central role of epithelial cells, through the dramatic phenotypic alterations observed in fibroblasts and the numerous aberrations that inflammatory cells exhibit. We end with reiterating a call for renewed efforts to collect and analyze carefully characterized human tissues, in ways that would facilitate implementation of novel technologies for high resolution single cell omics profiling.]]>
Wed, 31 Dec 1969 19:00:00 EST
ChromTime: modeling spatio-temporal dynamics of chromatin marks. Fiziev P, Ernst J
Genome Biol (Aug 2018)

To model spatial changes of chromatin mark peaks over time we develop and apply ChromTime, a computational method that predicts peaks to be either expanding, contracting, or holding steady between time points. Predicted expanding and contracting peaks can mark regulatory regions associated with transcription factor binding and gene expression changes. Spatial dynamics of peaks provide information about gene expression changes beyond localized signal density changes. ChromTime detects asymmetric expansions and contractions, which for some marks associate with the direction of transcription. ChromTime facilitates the analysis of time course chromatin data in a range of biological systems.]]>
Wed, 31 Dec 1969 19:00:00 EST
Computational Approaches and Related Tools to Identify MicroRNAs in a Species: A Bird's Eye View. Rajendiran A, Chatterjee A, Pan A
Interdiscip Sci (Sep 2018)

MicroRNAs (miRNAs) are a family of non-coding RNAs that play a central role in fine-tuning gene expression regulation. Over the past decade, identification and annotation of miRNAs have become a major focus in epigenomics research. However, detection and characterization of miRNA are challenging due to its small size (~22 nucleotide-long) and susceptibility to degradation. The difficulties involved in experimental prediction and characterization of miRNA coding genes have led to the development of in silico-based approaches. Although several algorithms have been developed in recent years, a comprehensive assessment of the principles, methodological insights, and estimate of the strengths and weaknesses of computational methods are limited. The present review is dealt with the detailed methodological insights of different tools used for identifying miRNA coding genes falling under four computational approaches. The parameters considered in these tools along with their specificity are also delineated. Furthermore, the strengths and weaknesses of these four computational approaches, and the bioinformatics resources pertaining to target identification, expression analysis, regulatory network analysis, and SNP identification are stated in this review. The methodological details of miRNA prediction methods and bioinformatics resources related to miRNA research in one platform would facilitate the miRNA research community to develop efficient tools for uncovering novel miRNAs and understanding their role in regulatory networks.]]>
Wed, 31 Dec 1969 19:00:00 EST
Transcription factor ASCL2 is required for development of the glycogen trophoblast cell lineage. Bogutz AB, Oh-McGinnis R, Jacob KJ, Ho-Lau R, Gu T, Gertsenstein M, Nagy A, Lefebvre L
PLoS Genet (Aug 2018)

The basic helix-loop-helix (bHLH) transcription factor ASCL2 plays essential roles in diploid multipotent trophoblast progenitors, intestinal stem cells, follicular T-helper cells, as well as during epidermal development and myogenesis. During early development, Ascl2 expression is regulated by genomic imprinting and only the maternally inherited allele is transcriptionally active in trophoblast. The paternal allele-specific silencing of Ascl2 requires expression of the long non-coding RNA Kcnq1ot1 in cis and the deposition of repressive histone marks. Here we show that Del7AI, a 280-kb deletion allele neighboring Ascl2, interferes with this process in cis and leads to a partial loss of silencing at Ascl2. Genetic rescue experiments show that the low level of Ascl2 expression from the paternal Del7AI allele can rescue the embryonic lethality associated with maternally inherited Ascl2 mutations, in a level-dependent manner. Despite their ability to support development to term, the rescued placentae have a pronounced phenotype characterized by severe hypoplasia of the junctional zone, expansion of the parietal trophoblast giant cell layer, and complete absence of invasive glycogen trophoblast cells. Transcriptome analysis of ectoplacental cones at E7.5 and differentiation assays of Ascl2 mutant trophoblast stem cells show that ASCL2 is required for the emergence or early maintenance of glycogen trophoblast cells during development. Our work identifies a new cis-acting mutation interfering with Kcnq1ot1 silencing function and establishes a novel critical developmental role for the transcription factor ASCL2.]]>
Wed, 31 Dec 1969 19:00:00 EST
Prospective Isolation of Poised iPSC Intermediates Reveals Principles of Cellular Reprogramming. Schwarz BA, Cetinbas M, Clement K, Walsh RM, Cheloufi S, Gu H, Langkabel J, Kamiya A, Schorle H, Meissner A, Sadreyev RI, Hochedlinger K
Cell Stem Cell (Aug 2018)

Cellular reprogramming converts differentiated cells into induced pluripotent stem cells (iPSCs). However, this process is typically very inefficient, complicating mechanistic studies. We identified and molecularly characterized rare, early intermediates poised to reprogram with up to 95% efficiency, without perturbing additional genes or pathways, during iPSC generation from mouse embryonic fibroblasts. Analysis of these cells uncovered transcription factors (e.g., Tfap2c and Bex2) that are important for reprogramming but dispensable for pluripotency maintenance. Additionally, we observed striking patterns of chromatin hyperaccessibility at pluripotency loci, which preceded gene expression in poised intermediates. Finally, inspection of these hyperaccessible regions revealed an early wave of DNA demethylation that is uncoupled from de novo methylation of somatic regions late in reprogramming. Our study underscores the importance of investigating rare intermediates poised to produce iPSCs, provides insights into reprogramming mechanisms, and offers a valuable resource for the dissection of transcriptional and epigenetic dynamics intrinsic to cell fate change.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenetic and Cellular Diversity in the Brain through Allele-Specific Effects. Huang WC, Bennett K, Gregg C
Trends Neurosci (Aug 2018)

The benefits of diploidy are considered to involve masking partially recessive mutations and increasing genetic diversity. Here, we review new studies showing evidence for diverse allele-specific expression and epigenetic states in mammalian brain cells, which suggest that diploidy expands the landscape of gene regulatory and expression programs in cells. Allele-specific expression has been thought to be restricted to a few specific classes of genes. However, new studies show novel genomic imprinting effects that are brain-region-, cell-type- and age-dependent. In addition, novel forms of random monoallelic expression that impact many autosomal genes have been described in vitro and in vivo. We discuss the implications for understanding the benefits of diploidy, and the mechanisms shaping brain development, function, and disease.]]>
Wed, 31 Dec 1969 19:00:00 EST
Biospecimens and the ABCD study: Rationale, methods of collection, measurement and early data. Uban KA, Horton MK, Jacobus J, Heyser C, Thompson WK, Tapert SF, Madden PAF, Sowell ER,  
Dev Cogn Neurosci (Aug 2018)

Biospecimen collection in the Adolescent Brain Cognitive Development (ABCD) study - of hair samples, shed deciduous (baby) teeth, and body fluids - will serve dual functions of screening for study eligibility, and providing measures of biological processes thought to predict or correlate with key study outcomes on brain and cognitive development. Biosamples are being collected annually to screen for recency of drug use prior to the neuroimaging or cognitive testing visit, and to store for the following future studies: (1) on the effects of exposure to illicit and recreational drugs (including alcohol and nicotine); (2) of pubertal hormones on brain and cognitive developmental trajectories; (3) on the contribution of genomics and epigenomics to child and adolescent development and behavioral outcomes; and (4) with pre- and post-natal exposure to environmental neurotoxicants and drugs of abuse measured from novel tooth analyses. The present manuscript describes the rationales for inclusion and selection of the specific biospecimens, methodological considerations for each measure, future plans for assessment of biospecimens during follow-up visits, and preliminary ABCD data to illustrate methodological considerations.]]>
Wed, 31 Dec 1969 19:00:00 EST
Processing of big heterogeneous genomic datasets for tertiary analysis of Next Generation Sequencing data. Masseroli M, Canakoglu A, Pinoli P, Kaitoua A, Gulino A, Horlova O, Nanni L, Bernasconi A, Perna S, Stamoulakatou E, Ceri S
Bioinformatics (Aug 2018)

We previously proposed a paradigm shift in genomic data management, based on the Genomic Data Model (GDM) for mediating existing data formats and on the GenoMetric Query Language (GMQL) for supporting, at a high level of abstraction, data extraction and the most common data-driven computations required by tertiary data analysis of Next Generation Sequencing datasets. Here, we present a new GMQL-based system with enhanced accessibility, portability, scalability and performance.]]>
Wed, 31 Dec 1969 19:00:00 EST
Heritable Epigenomic Changes to the Maize Methylome Resulting from Tissue Culture. Han Z, Crisp PA, Stelpflug S, Kaeppler SM, Li Q, Springer NM
Genetics (08 2018)

DNA methylation can contribute to the maintenance of genome integrity and regulation of gene expression. In most situations, DNA methylation patterns are inherited quite stably. However, changes in DNA methylation can occur at some loci as a result of tissue culture resulting in somaclonal variation. To investigate heritable epigenetic changes as a consequence of tissue culture, a sequence-capture bisulfite sequencing approach was implemented to monitor context-specific DNA methylation patterns in ∼15 Mb of the maize genome for a population of plants that had been regenerated from tissue culture. Plants that have been regenerated from tissue culture exhibit gains and losses of DNA methylation at a subset of genomic regions. There was evidence for a high rate of homozygous changes to DNA methylation levels that occur consistently in multiple independent tissue culture lines, suggesting that some loci are either targeted or hotspots for epigenetic variation. The consistent changes inherited following tissue culture include both gains and losses of DNA methylation and can affect CG, CHG, or both contexts within a region. Only a subset of the tissue culture changes observed in callus plants are observed in the primary regenerants, but the majority of DNA methylation changes present in primary regenerants are passed onto offspring. This study provides insights into the susceptibility of some loci and potential mechanisms that could contribute to altered DNA methylation and epigenetic state that occur during tissue culture in plant species.]]>
Wed, 31 Dec 1969 19:00:00 EST
Single-cell RNA sequencing technologies and bioinformatics pipelines. Hwang B, Lee JH, Bang D
Exp Mol Med (Aug 2018)

Rapid progress in the development of next-generation sequencing (NGS) technologies in recent years has provided many valuable insights into complex biological systems, ranging from cancer genomics to diverse microbial communities. NGS-based technologies for genomics, transcriptomics, and epigenomics are now increasingly focused on the characterization of individual cells. These single-cell analyses will allow researchers to uncover new and potentially unexpected biological discoveries relative to traditional profiling methods that assess bulk populations. Single-cell RNA sequencing (scRNA-seq), for example, can reveal complex and rare cell populations, uncover regulatory relationships between genes, and track the trajectories of distinct cell lineages in development. In this review, we will focus on technical challenges in single-cell isolation and library preparation and on computational analysis pipelines available for analyzing scRNA-seq data. Further technical improvements at the level of molecular and cell biology and in available bioinformatics tools will greatly facilitate both the basic science and medical applications of these sequencing technologies.]]>
Wed, 31 Dec 1969 19:00:00 EST
Characterization of Imprinted Genes in Rice Reveals Conservation of Regulation and Imprinting with Other Plant Species. Chen C, Li T, Zhu S, Liu Z, Shi Z, Zheng X, Chen R, Huang J, Shen Y, Luo S, Wang L, Liu QQ, E Z
Plant Physiol (Aug 2018)

Genomic imprinting is an epigenetic phenomenon by which certain genes display differential expression in a parent-of-origin-dependent manner. Hundreds of imprinted genes have been identified from several plant species. Here, we identified, with a high level of confidence, 208 imprinted gene candidates from rice (). Imprinted genes of rice showed limited association with the transposable elements, which contrasts with findings from Arabidopsis (). Generally, imprinting in rice is conserved within a species, but intraspecific variation also was detected. The imprinted rice genes do not show signatures of selection, which suggests that domestication has had a limited evolutionary consequence on genomic imprinting. Although conservation of imprinting in plants is limited, we show that some loci are imprinted in several different species. Moreover, our results suggest that different types of epigenetic regulation can be established either before or after fertilization. Imprinted 24-nucleotide small RNAs and their neighboring genes tend to express alleles from different parents. This association was not observed between 21-nucleotide small RNAs and their neighboring genes. Together, our findings suggest that the regulation of imprinting can be diverse, and genomic imprinting has evolutionary and biological significance.]]>
Wed, 31 Dec 1969 19:00:00 EST
Maintenance of grafting-induced epigenetic variations in the asexual progeny of Brassica oleracea and B. juncea chimera. Yu N, Cao L, Yuan L, Zhi X, Chen Y, Gan S, Chen L
Plant J (Aug 2018)

Grafting-induced variations have been observed in many plant species, but the heritability of variation in progeny is not well understood. In our study, adventitious shoots from the C cell lineage of shoot apical meristem (SAM) grafting chimera TCC (where the origin of the outmost, middle and innermost cell layers, respectively, of SAM is designated by 'T' for tuber mustard and 'C' for red cabbage) were induced and identified as r-CCC (r = regenerated). To investigate the maintenance of grafting variations during cell propagation and regeneration, different generations of asexual progeny (r-CCCn, n = generation) were established through successive regeneration of axillary shoots from r-CCC. The fourth generation of r-CCC (r-CCC4) was selected to perform whole genome bisulfite sequencing for comparative analysis of hetero-grafting induced global methylation changes relative to r-s-CCC4 (s = self-grafting). Increased CHH methylation levels and proportions were observed in r-CCC4, with substantial changes occurring in the repeat elements. Small RNA sequencing revealed 1,135 specific small interfering RNA (siRNA) tags that were typically expressed in r-CCC, r-CCC2 and r-CCC4. Notably, 65% of these specific siRNAs were associated with repeat elements, termed RE siRNAs. Subsequent analysis revealed the CHH methylation of RE siRNA overlapping regions were mainly hypermethylated in r-CCC4, indicating they were responsible for directing and maintaining grafting-induced CHH methylation. Moreover, the expression of 13 differentially methylated genes (DMGs) correlated with the phenotypic variation, showing differential expression levels between r-CCC4 and r-s-CCC4. These DMGs were predominantly CG hypermethylated, their methylation modifications corresponded to the transcription of relative methyltransferase. This article is protected by copyright. All rights reserved.]]>
Wed, 31 Dec 1969 19:00:00 EST
Imprint stability and plasticity during development. Mackin SJ, Thakur A, Walsh CP
Reproduction (08 2018)

There have been a number of recent insights in the area of genomic imprinting, the phenomenon whereby one of two autosomal alleles is selected for expression based on the parent of origin. This is due in part to a proliferation of new techniques for interrogating the genome that are leading researchers working on organisms other than mouse and human, where imprinting has been most studied, to become interested in looking for potential imprinting effects. Here, we recap what is known about the importance of imprints for growth and body size, as well as the main types of locus control. Interestingly, work from a number of labs has now shown that maintenance of the imprint post implantation appears to be a more crucial step than previously appreciated. We ask whether imprints can be reprogrammed somatically, how many loci there are and how conserved imprinted regions are in other species. Finally, we survey some of the methods available for examining DNA methylation genome-wide and look to the future of this burgeoning field.]]>
Wed, 31 Dec 1969 19:00:00 EST