scholarly journals Transposable elements contribute to the genomic response to insecticides in Drosophila melanogaster

2020 ◽  
Vol 375 (1795) ◽  
pp. 20190341 ◽  
Author(s):  
Judit Salces-Ortiz ◽  
Carlos Vargas-Chavez ◽  
Lain Guio ◽  
Gabriel E. Rech ◽  
Josefa González
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Regulatory Networks ◽  
Regulation Of Gene Expression ◽  
Nucleotide Polymorphisms ◽  
Rna Seq ◽  
Organophosphate Insecticide ◽  
Single Nucleotide ◽  
Insecticide Exposure ◽  
Genomic Response

Most of the genotype–phenotype analyses to date have largely centred attention on single nucleotide polymorphisms. However, transposable element (TE) insertions have arisen as a plausible addition to the study of the genotypic–phenotypic link because of to their role in genome function and evolution. In this work, we investigate the contribution of TE insertions to the regulation of gene expression in response to insecticides. We exposed four Drosophila melanogaster strains to malathion, a commonly used organophosphate insecticide. By combining information from different approaches, including RNA-seq and ATAC-seq, we found that TEs can contribute to the regulation of gene expression under insecticide exposure by rewiring cis -regulatory networks. This article is part of a discussion meeting issue ‘Crossroads between transposons and gene regulation’.

scholarly journals Automated generation of context-specific gene regulatory networks with a weighted approach in Drosophila melanogaster

2021 ◽  
Vol 11 (4) ◽  
pp. 20200076 ◽  
Author(s):  
Leandro Murgas ◽  
Sebastian Contreras-Riquelme ◽  
J. Eduardo Martínez-Hernandez ◽  
Camilo Villaman ◽  
Rodrigo Santibáñez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Reference Network ◽  
Specific Gene ◽  
Gene Regulatory ◽  
Context Specific

The regulation of gene expression is a key factor in the development and maintenance of life in all organisms. Even so, little is known at whole genome scale for most genes and contexts. We propose a method, Tool for Weighted Epigenomic Networks in Drosophila melanogaster (Fly T-WEoN), to generate context-specific gene regulatory networks starting from a reference network that contains all known gene regulations in the fly. Unlikely regulations are removed by applying a series of knowledge-based filters. Each of these filters is implemented as an independent module that considers a type of experimental evidence, including DNA methylation, chromatin accessibility, histone modifications and gene expression. Fly T-WEoN is based on heuristic rules that reflect current knowledge on gene regulation in D. melanogaster obtained from the literature. Experimental data files can be generated with several standard procedures and used solely when and if available. Fly T-WEoN is available as a Cytoscape application that permits integration with other tools and facilitates downstream network analysis. In this work, we first demonstrate the reliability of our method to then provide a relevant application case of our tool: early development of D. melanogaster . Fly T-WEoN together with its step-by-step guide is available at https://weon.readthedocs.io .

scholarly journals Whole Blood Transcriptome Sequencing Reveals Gene Expression Differences between Dapulian and Landrace Piglets

2016 ◽  
Vol 2016 ◽  
pp. 1-10
Author(s):  
Jiaqing Hu ◽  
Dandan Yang ◽  
Wei Chen ◽  
Chuanhao Li ◽  
Yandong Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Whole Blood ◽  
Molecular Mechanisms ◽  
Future Research ◽  
Nucleotide Polymorphisms ◽  
Rna Seq ◽  
Single Nucleotide ◽  
Neonatal Stage ◽  
Pathway Analyses ◽  
Blood Transcriptome

There is little genomic information regarding gene expression differences at the whole blood transcriptome level of different pig breeds at the neonatal stage. To solve this, we characterized differentially expressed genes (DEGs) in the whole blood of Dapulian (DPL) and Landrace piglets using RNA-seq (RNA-sequencing) technology. In this study, 83 DEGs were identified between the two breeds. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses identified immune response and metabolism as the most commonly enriched terms and pathways in the DEGs. Genes related to immunity and lipid metabolism were more highly expressed in the DPL piglets, while genes related to body growth were more highly expressed in the Landrace piglets. Additionally, the DPL piglets had twofold more single nucleotide polymorphisms (SNPs) and alternative splicing (AS) than the Landrace piglets. These results expand our knowledge of the genes transcribed in the piglet whole blood of two breeds and provide a basis for future research of the molecular mechanisms underlying the piglet differences.

scholarly journals Determination of novel members in the Drosophila melanogaster anteriorposterior patterning system using natural variation

2018 ◽  
Author(s):  
Ashley A. Jermusyk ◽  
Sarah E. Gharavi ◽  
Aslesha S. Tingare ◽  
Gregory T. Reeves
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Transcription Factors ◽  
Natural Variation ◽  
Expression Patterns ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Gap Gene ◽  
Drosophila Genetic Reference Panel

AbstractThe anterior-posterior axis of the developing Drosophila melanogaster embryo is patterned by a well-studied gene regulatory network called the Gap Gene Network. This network acts to buffer the developing pattern against noise, thereby minimizing errors in gene expression and preventing patterning defects.In this paper, we sought to discover novel regulatory regions and transcription factors acting in a subset of the Gap network using a selection of wild-caught fly lines derived from the Drosophila Genetic Reference Panel (DGRP). The fly lines in the DGRP contain subtle genomic differences due to natural variation; we quantified the differences in positioning of gene expression borders of two anterior-poster patterning genes, Krüppel (Kr) and Even-skipped in 13 of the DGRP lines. The differences in the positions of Krüppel and Even-skipped were then correlated to specific single nucleotide polymorphisms and insertions/deletions within the select fly lines. Putative enhancers containing these genomic differences were validated for their ability to produce expression using reporter constructs and analyzed for possible transcription factor binding sites. The identified transcription factors were then perturbed and the resulting Eve and Kr positioning was determined. In this way, we found medea, ultraspiracle, glial cells missing, and orthopedia effect Kr and Eve positioning in subtle ways, while knock-down of pangolin produces significant shifts in Kr and subsequent Eve expression patterns. Most importantly this study points to the existence of many additional novel members that have subtle effects on this system and the degree of complexity that is present in patterning the developing embryo.

scholarly journals Natural genetic variation affecting transcription factor spacing at regulatory regions is generally well tolerated

2020 ◽  
Author(s):  
Zeyang Shen ◽  
Jenhan Tao ◽  
Gregory J. Fonseca ◽  
Christopher K. Glass
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Binding Sites ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
Nucleotide Polymorphisms ◽  
Enhancer Activity ◽  
Single Nucleotide ◽  
Natural Genetic Variation ◽  
Influence Gene Expression

AbstractRegulation of gene expression requires the combinatorial binding of sequence-specific transcription factors (TFs) at promoters and enhancers. Single nucleotide polymorphisms (SNPs) and short insertions and deletions (InDels) can influence gene expression by altering the sequences of TF binding sites. Prior studies also showed that alterations in the spacing between TF binding sites can influence promoter and enhancer activity. However, the relative importance of altered TF spacing has not been systematically analyzed in the context of natural genetic variation. Here, we exploit millions of InDels provided by five diverse strains of mice to globally investigate the effects of altered spacing on TF binding and local histone acetylation in macrophages. We find that spacing alterations resulting from InDels are generally well tolerated in comparison to genetic variants that directly alter TF binding sites. These findings have implications for interpretation of non-coding genetic variation and comparative analysis of regulatory elements across species.

scholarly journals Investigation of allele specific expression in various tissues of broiler chickens using the detection tool VADT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. Joseph Tomlinson ◽  
Shawn W. Polson ◽  
Jing Qiu ◽  
Juniper A. Lake ◽  
William Lee ◽  
...  
Keyword(s):  
Broiler Chickens ◽  
Nucleotide Polymorphisms ◽  
Rna Seq ◽  
Specific Expression ◽  
Single Nucleotide ◽  
Allele Specific Expression ◽  
Detection Tool ◽  
Commercial Broiler ◽  
Significant Phenomenon ◽  
Allele Specific

AbstractDifferential abundance of allelic transcripts in a diploid organism, commonly referred to as allele specific expression (ASE), is a biologically significant phenomenon and can be examined using single nucleotide polymorphisms (SNPs) from RNA-seq. Quantifying ASE aids in our ability to identify and understand cis-regulatory mechanisms that influence gene expression, and thereby assist in identifying causal mutations. This study examines ASE in breast muscle, abdominal fat, and liver of commercial broiler chickens using variants called from a large sub-set of the samples (n = 68). ASE analysis was performed using a custom software called VCF ASE Detection Tool (VADT), which detects ASE of biallelic SNPs using a binomial test. On average ~ 174,000 SNPs in each tissue passed our filtering criteria and were considered informative, of which ~ 24,000 (~ 14%) showed ASE. Of all ASE SNPs, only 3.7% exhibited ASE in all three tissues, with ~ 83% showing ASE specific to a single tissue. When ASE genes (genes containing ASE SNPs) were compared between tissues, the overlap among all three tissues increased to 20.1%. Our results indicate that ASE genes show tissue-specific enrichment patterns, but all three tissues showed enrichment for pathways involved in translation.

scholarly journals The role of 25-hydroxyvitamin-D3 and vitamin D receptor gene in human periodontal ligament fibroblasts as response to orthodontic compressive strain: an in vitro study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Erika Calvano Küchler ◽  
Agnes Schröder ◽  
Vinicius Broska Teodoro ◽  
Ute Nazet ◽  
Rafaela Scariot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Single Nucleotide Polymorphisms ◽  
Periodontal Ligament ◽  
Compressive Strain ◽  
Nucleotide Polymorphisms ◽  
Periodontal Ligament Fibroblasts ◽  
Single Nucleotide ◽  
Cox 2

Abstract Background This study aimed to investigate, if different physiological concentrations of vitamin D (25(OH)D3) and single nucleotide polymorphisms in vitamin D receptor (VDR) gene have an impact on gene expression in human periodontal ligament (hPDL) fibroblasts induced by simulated orthodontic compressive strain. Methods A pool of hPDL fibroblasts was treated in absence or presence of 25(OH)D3 in 3 different concentrations (10, 40 and 60 ng/ml). In order to evaluate the role of single nucleotide polymorphisms in the VDR gene, hPDL fibroblasts from 9 patients were used and treated in absence or presence of 40 ng/ml 25(OH)D3. Each experiment was performed with and without simulated orthodontic compressive strain. Real-time PCR was used for gene expression and allelic discrimination analysis. Relative expression of dehydrocholesterol reductase (DHCR7), Sec23 homolog A, amidohydrolase domain containing 1 (AMDHD1), vitamin D 25-hydroxylase (CYP2R1), Hydroxyvitamin D-1-α hydroxylase, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), cyclooxygenase-2 (COX-2) and interleukin-6 (IL6) was assessed. Three single nucleotide polymorphisms in VDR were genotyped. Parametric or non-parametric tests were used with an alpha of 5%. Results RANKL, RANKL:OPG ratio, COX-2, IL-6, DHCR7, CYP2R1 and AMDHD1 were differentially expressed during simulated orthodontic compressive strain (p < 0.05). The RANKL:OPG ratio was downregulated by all concentrations (10 ng/ml, 40 ng/ml and 60 ng/ml) of 25(OH)D3 (mean = 0.96 ± 0.68, mean = 1.61 ± 0.66 and mean = 1.86 ± 0.78, respectively) in comparison to the control (mean 2.58 ± 1.16) (p < 0.05). CYP2R1 gene expression was statistically modulated by the different 25(OH)D3 concentrations applied (p = 0.008). Samples from individuals carrying the GG genotype in rs739837 presented lower VDR mRNA expression and samples from individuals carrying the CC genotype in rs7975232 presented higher VDR mRNA expression (p < 0.05). Conclusions Simulated orthodontic compressive strain and physiological concentrations of 25(OH)D3 seem to regulate the expression of orthodontic tooth movement and vitamin-D-related genes in periodontal ligament fibroblasts in the context of orthodontic compressive strain. Our study also suggests that single nucleotide polymorphisms in the VDR gene regulate VDR expression in periodontal ligament fibroblasts in the context of orthodontic compressive strain.

scholarly journals Complex fibroblast response to glucocorticoids may underlie variability of clinical efficacy in the vocal folds

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ryosuke Nakamura ◽  
Shigeyuki Mukudai ◽  
Renjie Bing ◽  
Michael J. Garabedian ◽  
Ryan C. Branski
Keyword(s):  
Gene Expression ◽  
Transforming Growth Factor ◽  
Regulation Of Gene Expression ◽  
Vocal Folds ◽  
Global Changes ◽  
Rna Seq ◽  
Fibrotic Response ◽  
Group A ◽  
Tgf Β1 ◽  
Nuclear Receptor Subfamily

AbstractSimilar to the hypertrophic scar and keloids, the efficacy of glucorticoids (GC) for vocal fold injury is highly variable. We previously reported dexamethasone enhanced the pro-fibrotic effects of transforming growth factor (TGF)-β as a potential mechanism for inconsistent clinical outcomes. In the current study, we sought to determine the mechanism(s) whereby GCs influence the fibrotic response and mechanisms underlying these effects with an emphasis on TGF-β and nuclear receptor subfamily 4 group A member 1 (NR4A1) signaling. Human VF fibroblasts (HVOX) were treated with three commonly-employed GCs+ /-TGF-β1. Phosphorylation of the glucocorticoid receptor (GR:NR3C1) and activation of NR4A1 was analyzed by western blotting. Genes involved in the fibrotic response, including ACTA2, TGFBR1, and TGFBR2 were analyzed by qPCR. RNA-seq was performed to identify global changes in gene expression induced by dexamethasone. GCs enhanced phosphorylation of GR at Ser211 and TGF-β-induced ACTA2 expression. Dexamethasone upregulated TGFBR1, and TGFBR2 in the presence of TGF-β1 and increased active NR4A1. RNA-seq results confirmed numerous pathways, including TGF-β signaling, affected by dexamethasone. Synergistic pro-fibrotic effects of TGF-β were observed across GCs and appeared to be mediated, at least partially, via upregulation of TGF-β receptors. Dexamethasone exhibited diverse regulation of gene expression including NR4A1 upregulation consistent with the anti-fibrotic potential of GCs.

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