scholarly journals Environmental influences on the epigenomes of herpetofauna and fish

2016 ◽  
Vol 94 (2) ◽  
pp. 95-100 ◽  
Author(s):  
S. Austin Hammond ◽  
Christopher J. Nelson ◽  
Caren C. Helbing
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Large Scale ◽  
Gene Expression Regulation ◽  
Genomic Sequence ◽  
Global Changes ◽  
Sequence Information ◽  
Health It ◽  
Species Specific ◽  
The Impact

Herpetofauna (amphibians and reptiles) and fish represent important sentinel and indicator species for environmental and ecosystem health. It is widely accepted that the epigenome plays an important role in gene expression regulation. Environmental stimuli, including temperature and pollutants, influence gene activity, and there is growing evidence demonstrating that an important mechanism is through modulation of the epigenome. This has been primarily studied in human and mammalian models; relatively little is known about the impact of environmental conditions or pollutants on herpetofauna or fish epigenomes and the regulatory consequences of these changes on gene expression. Herein we review recent studies that have begun to address this deficiency, which have mainly focused on limited specific epigenetic marks and individual genes or large-scale global changes in DNA methylation, owing to the comparative ease of measurement. Greater understanding of the epigenetic influences of these environmental factors will depend on increased availability of relevant species-specific genomic sequence information to facilitate chromatin immunoprecipitation and DNA methylation experiments.

scholarly journals Cell–cell coupling and DNA methylation abnormal phenotypes in the after-hours mice

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Federico Tinarelli ◽  
Elena Ivanova ◽  
Ilaria Colombi ◽  
Erica Barini ◽  
Edoardo Balzani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Neuronal Networks ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Neuronal Cultures ◽  
Functional Impairments ◽  
After Hours ◽  
The Impact

Abstract Background DNA methylation has emerged as an important epigenetic regulator of brain processes, including circadian rhythms. However, how DNA methylation intervenes between environmental signals, such as light entrainment, and the transcriptional and translational molecular mechanisms of the cellular clock is currently unknown. Here, we studied the after-hours mice, which have a point mutation in the Fbxl3 gene and a lengthened circadian period. Methods In this study, we used a combination of in vivo, ex vivo and in vitro approaches. We measured retinal responses in Afh animals and we have run reduced representation bisulphite sequencing (RRBS), pyrosequencing and gene expression analysis in a variety of brain tissues ex vivo. In vitro, we used primary neuronal cultures combined to micro electrode array (MEA) technology and gene expression. Results We observed functional impairments in mutant neuronal networks, and a reduction in the retinal responses to light-dependent stimuli. We detected abnormalities in the expression of photoreceptive melanopsin (OPN4). Furthermore, we identified alterations in the DNA methylation pathways throughout the retinohypothalamic tract terminals and links between the transcription factor Rev-Erbα and Fbxl3. Conclusions The results of this study, primarily represent a contribution towards an understanding of electrophysiological and molecular phenotypic responses to external stimuli in the Afh model. Moreover, as DNA methylation has recently emerged as a new regulator of neuronal networks with important consequences for circadian behaviour, we discuss the impact of the Afh mutation on the epigenetic landscape of circadian biology.

scholarly journals Pervasive cis effects of variation in copy number of large tandem repeats on local epigenetics and gene expression

2020 ◽  
Author(s):  
Paras Garg ◽  
Alejandro Martin-Trujillo ◽  
Oscar L. Rodriguez ◽  
Scott J. Gies ◽  
Bharati Jadhav ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Copy Number ◽  
Large Scale ◽  
Tandem Repeats ◽  
Local Variation ◽  
Read Depth ◽  
Variable Number ◽  
Human Populations ◽  
Functional Variation

ABSTRACTVariable Number Tandem Repeats (VNTRs) are composed of large tandemly repeated motifs, many of which are highly polymorphic in copy number. However, due to their large size and repetitive nature, they remain poorly studied. To investigate the regulatory potential of VNTRs, we used read-depth data from Illumina whole genome sequencing to perform association analysis between copy number of ~70,000 VNTRs (motif size ≥10bp) with both gene expression (404 samples in 48 tissues) and DNA methylation (235 samples in peripheral blood), identifying thousands of VNTRs that are associated with local gene expression (eVNTRs) and DNA methylation levels (mVNTRs). Using large-scale replication analysis in an independent cohort we validated 73-80% of signals observed in the two discovery cohorts, providing robust evidence to support that these represent genuine associations. Further, conditional analysis indicated that many eVNTRs and mVNTRs act as QTLs independently of other local variation. We also observed strong enrichments of eVNTRs and mVNTRs for regulatory features such as enhancers and promoters. Using the Human Genome Diversity Panel, we defined sets of VNTRs that show highly divergent copy numbers among human populations, show that these are enriched for regulatory effects on gene expression and epigenetics, and preferentially associate with genes that have been linked with human phenotypes through GWAS. Our study provides strong evidence supporting functional variation at thousands of VNTRs, and defines candidate sets of VNTRs, copy number variation of which potentially plays a role in numerous human phenotypes.

scholarly journals A comprehensive annotation and differential expression analysis of short and long non-coding RNAs in 16 bat genomes

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Nelly F Mostajo ◽  
Marie Lataretu ◽  
Sebastian Krautwurst ◽  
Florian Mock ◽  
Daniel Desirò ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Large Scale ◽  
Viral Infections ◽  
Gene Expression Regulation ◽  
Expression Patterns ◽  
Differential Expression Analysis ◽  
Regulatory Processes ◽  
Genome Annotations ◽  
Host Virus Interactions

Abstract Although bats are increasingly becoming the focus of scientific studies due to their unique properties, these exceptional animals are still among the least studied mammals. Assembly quality and completeness of bat genomes vary a lot and especially non-coding RNA (ncRNA) annotations are incomplete or simply missing. Accordingly, standard bioinformatics pipelines for gene expression analysis often ignore ncRNAs such as microRNAs or long antisense RNAs. The main cause of this problem is the use of incomplete genome annotations. We present a complete screening for ncRNAs within 16 bat genomes. NcRNAs affect a remarkable variety of vital biological functions, including gene expression regulation, RNA processing, RNA interference and, as recently described, regulatory processes in viral infections. Within all investigated bat assemblies, we annotated 667 ncRNA families including 162 snoRNAs and 193 miRNAs as well as rRNAs, tRNAs, several snRNAs and lncRNAs, and other structural ncRNA elements. We validated our ncRNA candidates by six RNA-Seq data sets and show significant expression patterns that have never been described before in a bat species on such a large scale. Our annotations will be usable as a resource (rna.uni-jena.de/supplements/bats) for deeper studying of bat evolution, ncRNAs repertoire, gene expression and regulation, ecology and important host–virus interactions.

scholarly journals Dissecting heterogeneous cell populations across drug and disease conditions with PopAlign

2020 ◽  
Vol 117 (46) ◽  
pp. 28784-28794
Author(s):  
Sisi Chen ◽  
Paul Rivaud ◽  
Jong H. Park ◽  
Tiffany Tsou ◽  
Emeric Charles ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Large Scale ◽  
Probabilistic Models ◽  
Single Cells ◽  
Measurement Techniques ◽  
Patient Specific ◽  
Cell Populations ◽  
Cell Measurement ◽  
The Impact

Single-cell measurement techniques can now probe gene expression in heterogeneous cell populations from the human body across a range of environmental and physiological conditions. However, new mathematical and computational methods are required to represent and analyze gene-expression changes that occur in complex mixtures of single cells as they respond to signals, drugs, or disease states. Here, we introduce a mathematical modeling platform, PopAlign, that automatically identifies subpopulations of cells within a heterogeneous mixture and tracks gene-expression and cell-abundance changes across subpopulations by constructing and comparing probabilistic models. Probabilistic models provide a low-error, compressed representation of single-cell data that enables efficient large-scale computations. We apply PopAlign to analyze the impact of 40 different immunomodulatory compounds on a heterogeneous population of donor-derived human immune cells as well as patient-specific disease signatures in multiple myeloma. PopAlign scales to comparisons involving tens to hundreds of samples, enabling large-scale studies of natural and engineered cell populations as they respond to drugs, signals, or physiological change.

scholarly journals Differential evolution in 3′UTRs leads to specific gene expression in Staphylococcus

2020 ◽  
Vol 48 (5) ◽  
pp. 2544-2563 ◽  
Author(s):  
Pilar Menendez-Gil ◽  
Carlos J Caballero ◽  
Arancha Catalan-Moreno ◽  
Naiara Irurzun ◽  
Inigo Barrio-Hernandez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Regulation ◽  
Bacterial Species ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Species Differentiation ◽  
Orthologous Genes ◽  
Genome Wide ◽  
Sequence Variations ◽  
Species Specific

Abstract The evolution of gene expression regulation has contributed to species differentiation. The 3′ untranslated regions (3′UTRs) of mRNAs include regulatory elements that modulate gene expression; however, our knowledge of their implications in the divergence of bacterial species is currently limited. In this study, we performed genome-wide comparative analyses of mRNAs encoding orthologous proteins from the genus Staphylococcus and found that mRNA conservation was lost mostly downstream of the coding sequence (CDS), indicating the presence of high sequence diversity in the 3′UTRs of orthologous genes. Transcriptomic mapping of different staphylococcal species confirmed that 3′UTRs were also variable in length. We constructed chimeric mRNAs carrying the 3′UTR of orthologous genes and demonstrated that 3′UTR sequence variations affect protein production. This suggested that species-specific functional 3′UTRs might be specifically selected during evolution. 3′UTR variations may occur through different processes, including gene rearrangements, local nucleotide changes, and the transposition of insertion sequences. By extending the conservation analyses to specific 3′UTRs, as well as the entire set of Escherichia coli and Bacillus subtilis mRNAs, we showed that 3′UTR variability is widespread in bacteria. In summary, our work unveils an evolutionary bias within 3′UTRs that results in species-specific non-coding sequences that may contribute to bacterial diversity.

The COP9 signalosome influences the epigenetic landscape of Arabidopsis thaliana

2018 ◽  
Vol 35 (16) ◽  
pp. 2718-2723 ◽  
Author(s):  
Tamir Tuller ◽  
Alon Diament ◽  
Avital Yahalom ◽  
Assaf Zemach ◽  
Shimshi Atar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Arabidopsis Thaliana ◽  
Gene Expression Regulation ◽  
Developmental Pathways ◽  
Cop9 Signalosome ◽  
Supplementary Information ◽  
Loss Of Function ◽  
Genome Wide ◽  
High Level

Abstract Motivation The COP9 signalosome is a highly conserved multi-protein complex consisting of eight subunits, which influences key developmental pathways through its regulation of protein stability and transcription. In Arabidopsis thaliana, mutations in the COP9 signalosome exhibit a number of diverse pleiotropic phenotypes. Total or partial loss of COP9 signalosome function in Arabidopsis leads to misregulation of a number of genes involved in DNA methylation, suggesting that part of the pleiotropic phenotype is due to global effects on DNA methylation. Results We determined and analyzed the methylomes and transcriptomes of both partial- and total-loss-of-function Arabidopsis mutants of the COP9 signalosome. Our results support the hypothesis that the COP9 signalosome has a global genome-wide effect on methylation and that this effect is at least partially encoded in the DNA. Our analyses suggest that COP9 signalosome-dependent methylation is related to gene expression regulation in various ways. Differentially methylated regions tend to be closer in the 3D conformation of the genome to differentially expressed genes. These results suggest that the COP9 signalosome has a more comprehensive effect on gene expression than thought before, and this is partially related to regulation of methylation. The high level of COP9 signalosome conservation among eukaryotes may also suggest that COP9 signalosome regulates methylation not only in plants but also in other eukaryotes, including humans. Supplementary information Supplementary data are available at Bioinformatics online.

152 SPECIES-SPECIFIC DIFFERENCES IN THE METHYLATION REPROGRAMMING DURING EARLY PRE-IMPLANTATION DEVELOPMENT

2017 ◽  
Vol 29 (1) ◽  
pp. 184
Author(s):  
S. Canovas ◽  
E. Ivanova ◽  
S. Garcia-Martinez ◽  
R. Romar ◽  
N. Fonseca-Balvis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Expression Profiles ◽  
Differential Expression Analysis ◽  
Gene Expression Pattern ◽  
Reproductive Technologies ◽  
Global Methylation ◽  
Species Specific

Studies in mouse and human have shown extensive DNA methylation reprogramming in pre-implantation development followed by remethylation from implantation. However, the extent to which such reprogramming is conserved in mammals and the timing of demethylation and remethylation are unknown. As part of a major objective to characterise methylation dynamics in the bovine and porcine species from the oocyte to the blastocyst stage, we aimed here to compare the distribution of methylation at single-base resolution in both species at Day 7.5 of development. The DNA methylation profiles were obtained from individual blastocysts at Day 7.5 [pig: 3 in vivo, 3 in vitro; cow: 3 in vivo, 3 in vitro, 3 inner cell mass (ICM) and 3 trophoectoderm (TE) dissected from in vitro blastocysts] using the post-bisulphite adaptor tagging method and Illumina sequencing. For oocytes, data (GEO: GSE63330) from Schroeder et al. 2015 were analysed. Raw sequences were mapped, methylation calls made using Bismark and data analysis and visualisation was done within the SeqMonk platform. Gene expression profiles from individual blastocysts (3 pig, 3 cow) were obtained by RNA-seq. Annotated mRNA features were quantitated in SeqMonk and these were fed into DESeq2 for differential expression analysis (P < 0.05) as previously reported (Love et al. 2014 Genome Biol. 15, 550). Global methylation levels in whole blastocysts differed substantially between porcine and bovine embryos (in vivo: 12.33 ± 3.6 v. 28.33 ± 3.5%; in vitro: 15.02 ± 3.3 v. 24.41 ± 4.1%). In addition, the distribution of methylation differed: the pattern of cytosine methylated seemed random in the porcine genome, but was highly structured in the bovine genome, with methylation predominantly over gene bodies, resembling the profile previously reported in oocytes (Schroeder et al. 2015 PLoS Genet. 11, e1005442). Regarding correlation analysis, gene expression versus methylation were plotted. It suggested that gene body methylation reflected gene expression pattern in oocytes as well as in bovine blastocysts. Pair-wise comparison of isolated ICM and TE was filtered to require 5% change, and replicate set statistics were applied. This revealed very similar total and regional methylation levels in the 2 compartments, indicating that remethylation does not initiate preferentially in one compartment in bovine pre-implantation embryos. This confirms, from a viewpoint of the genome-wide DNA methylation, what has been observed in mouse for specific genes: the trophoblast-specific DNA methylation occurs after the segregation of the TE and ICM (Nakanishi et al. 2012 Epigenetics 7, 173–183). Our study is the first to provide whole genome methylation profiles from single blastocysts of economically important livestock species. Our data demonstrate that methylation reprogramming in early pre-implantation development is species specific. Knowledge of these specific patterns may have high importance when decisions are taken regarding the use of assisted reproductive technologies, cloning, or generation of transgenic animals. This work was funded by AGL2015–66341-R (MINECO-FEDER), PRX14/00348 (MECD), 19595/EE/14 (F. Séneca).

scholarly journals Effects of hydraulic engineering restoration measures on invasive gobies in a large river (Danube, Austria)

2019 ◽  
Vol 22 (2) ◽  
pp. 437-453 ◽  
Author(s):  
David Ramler ◽  
Hubert Keckeis
Keyword(s):  
Large Scale ◽  
Population Control ◽  
Round Goby ◽  
Direct Methods ◽  
Large River ◽  
Invasive Species Control ◽  
General Decline ◽  
Species Specific ◽  
The Impact ◽  
Restoration Measures

Abstract Invasive gobies can have severe detrimental effects on local fish communities, however, direct methods for population control are often insufficient (i.e. fishing) or not feasible (i.e. poisoning). Indirect methods, such as habitat modifications in the course of restoration programs, appear promising but are poorly studied. In this study, we investigate the effects of different restoration measures on the abundance and occurrence of non-native gobies in the main stem of a free-flowing section of the Danube and attempt to disentangle these measures from general large-scale trends by applying a Before-After-Control-Impact design. We found three invasive goby species (racer, bighead, and round goby) in the sampling area, partly with very high abundances. Four to six years after the installation, the measures had negative (riprap removal), neutral (side arm reconnection), or positive (groyne field adaptations) effects on goby abundances. We conclude that the impact of the measures depends on the type of intervention, is species-specific, and is largely related to substrate composition. Independent from the effect of the measures, abundances of bighead and round goby dropped in the project and reference sections after the pre-survey. This general decline probably indicates a stabilization phase of the goby populations on a lower level, but may also be influenced by a major flood event. Nevertheless, our results indicate a high potential of shoreline modifications for invasive species control, calling for considering and incorporating them in river restoration programs.

Replicative Senescence-Associated Gene Expression Changes In Human MSPCs Independent of Genomic Variations

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4775-4775
Author(s):  
Katharina Schallmoser ◽  
Christina Bartmann ◽  
Eva Rohde ◽  
Simone Bork ◽  
Christian Guelly ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Culture ◽  
Bone Marrow ◽  
Large Scale ◽  
Replicative Senescence ◽  
Genomic Stability ◽  
The State ◽  
Efficient Treatment ◽  
The Impact

Abstract Abstract 4775 Background: Based on promising experimental studies with mesenchymal stem and progenitor cells (MSPCs) multiple clinical trials have been initiated. In previous studies we have observed genomic stability of MSPCs after efficient short-term expansion in a humanized GMP compliant system with pooled human platelet lysate (pHPL) replacing fetal bovine serum (FBS) as the cell culture supplement (Schallmoser K. and Strunk D., Journal of Visualized Experiments (32) DOI: 10.3791/1523, 2009). Notably, depending on culture protocols, an extensive propagation with highly variable cell culture duration may be necessary to yield enough MSPCs for therapy. The decline in proliferation rates of MSPCs in the course of the different long-term expansion procedures may indicate a propensity for replicative senescence which may hamper long term functionality in vivo. We have therefore initiated a molecular profiling of senescence-associated regulated genes to determine the state of senescence before MSPC transplantation. Methods: Human bone marrow-derived MSPCs were cultured following a highly efficient two-passage protocol (primary culture of unseparated bone marrow and subsequent large scale expansion; Schallmoser K. et al., Tissue Engineering 14:185-196, 2008) compared to conventional serial passaging in three different growth conditions with regularly more then four passages to obtain comparable final cell numbers. Culture media were either supplemented with FBS in different concentrations or pHPL. Gene expression changes were tested by microarray analysis and selected targets were reanalyzed by quantitative real-time PCR. The genomic stability of MSPCs after long-term culture was determined by array comparative genomic hybridization (CGH). Results: Despite high proliferation rate large scale expanded MSPCs showed genomic stability in array CGH. Long-term MSPC growth induced similar gene expression changes in MSPCs irrespective of isolation and expansion conditions. In particular, genes involved in cell differentiation, apoptosis and cell death were up-regulated, whereas genes involved in mitosis and proliferation were down-regulated. Furthermore, overlapping senescence-associated gene expression changes were found in all MSPC preparations. The genomic copy number variations detected in MSPCs of early and late passages in all culture conditions did not coincide with differentially expressed genes. Conclusion: Our data indicate that MSPC expansion can induce gene expression changes independent of isolation and FBS-supplemented as well as FBS-free expansion conditions. A panel of genes will be presented that might offer a practicable approach to assess MSPC quality with regard to the state of replicative senescence in advance of therapeutic application. Determining the impact of senescence acquired during cell expansion on the therapeutic potential of MSCPs for both immune modulation and organ regeneration may help to develop more efficient treatment strategies. Disclosures: No relevant conflicts of interest to declare.

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